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Poor Use of ICD-10 Rheumatology Codes Suggests New Approach Needed for ICD-11 Adoption
Inflammatory arthritis codes increased 30-fold in the transition from the ninth to the 10th revision of the International Classification of Diseases (ICD-9 and -10), yet few were used in clinical practice, according to new research.
Most of the new codes for inflammatory arthritis in ICD-10 were rarely used, if at all, from 2015 to 2021.
“About 10-20 codes were comprising the majority of usage for inflammatory arthritis patients in ICD-10,” first author Justin Zhu, a researcher and medical student at Yale University in New Haven, Connecticut, told this news organization. “The other 380 or 400 codes just weren’t seeing a lot of use.”
The findings show the difficulties of transitioning to a new system, he added, and emphasize the need for additional training to improve adoption of ICD-11. The new coding system launched globally in January 2022, but it is not clear when it will be implemented in the United States.
ICD-10 was launched in the United States in 2015, with the goal of enabling greater specificity in identifying health conditions. For example, the new coding system allowed users to include information on laterality and anatomic location for the first time. The total number of codes increased from 14,500 with ICD-9 to 70,000 with ICD-10, with the number of inflammatory arthritis diagnosis codes growing from 14 to 425.
To see how these ICD-10 codes were utilized compared with ICD-9, Zhu and colleagues used national multi-insurance administrative claims data to find inflammatory arthritis diagnostic codes for over 5.1 million patients. About half were coded in ICD-9, while the remaining half were coded in ICD-10. Mr. Zhu and colleagues defined “higher-usage codes” as those that were used more than 1% of the time.
The findings were published in a research letter in JAMA Network Open on April 18.
For ICD-9, four of the available 14 codes (28.6%) were higher-usage codes. In contrast, only nine of the 425 ICD-10 codes (2.1%) were frequently used. Though ICD-10 allowed for increased granularity in diagnosis, data showed that nonspecific codes were most popular. Of the 20 most used ICD-10 arthritis codes, 65% contained “unspecified or other specified” in its wording.
The researchers also found that there was no significant change in these higher-usage codes throughout the study period from 2015 to 2021, suggesting there was not a detectable learning curve in ICD-10 usage among physicians and coders. They also found that clinician specialty did not change code usage patterns.
“The percentage of codes used was not better for rheumatologists (who might be expected to be more refined users of such codes) than primary care clinicians,” Mr. Zhu and colleagues wrote.
Moving to ICD-11 Brings Challenges as Well as Opportunities
Mr. Zhu noted that the study highlights the challenges of adopting new technological systems into daily practice, which can inform the eventual transition to ICD-11.
“There is this need to emphasize training as well as just invest more in improving adoption of ICD-11,” he said.
Michael Pine, MD, MBA, of MJP Healthcare Innovations, LLC in Evanston, Illinois, added that ICD-11 needs to be more user-friendly to be useful in practice. While ICD-10 allowed for greater granularity in coding, it did not result in “usable granularity, in terms of the things doctors really want to communicate,” he told this news organization.
And the transition to ICD-11 could pose greater challenges; rather than ICD-10’s taxonomy system, ICD-11 is formatted as an ontology.
“Although ICD-11 retains some precoordinated codes that convey multifaceted compound concepts, its structure and syntax also provide for post-coordination, a new feature to the ICD that supports the customized combination of concepts and modifier codes to capture previously inaccessible clinical nuance,” he wrote in a coauthored invited commentary.
This added clinical nuance, however, will potentially make coding more complex, he said. One solution is to automate coding, such that clinicians could input information in a natural clinical format that makes sense to them, which would then be translated into ICD-11 code by a program. (This would then be translated back to the user in the natural clinical format to ensure accuracy.)
This type of process would limit how much any one person would need to know about ICD-11 to code diagnoses effectively, while also taking full advantage of the increasing specificity of the new coding system, he said.
Such a program does not yet exist but could be possible with intensive investment in the transition to ICD-11.
The findings of this study serve as a cautionary tale for future transitions to new systems without considering the importance of user experience and usability, Dr. Pine noted. If the United States takes an approach for the adoption of ICD-11 that is similar to that used for ICD-10, it is likely to be “just another overhyped transition” that will make users unwilling to adopt any new system moving forward out of frustration.
But if the United States takes a different, innovative approach, the opposite could be true.
“In short, the US must decide whether it is time to invest considerable resources and effort into a 21st-century information system that could overcome such hindrances as asymmetric information for decision-making, faulty risk adjustment in performance evaluations and payment formulas, and burdens imposed by current coding and documentation practices,” the commentary reads.
“It will allow us to make the best of what computers do and the best of what clinicians do,” Dr. Pine added, “and get them to work together in ways which would not have been conceivable 50 years ago.”
No information on study funding was provided. Mr. Zhu and Dr. Pine did not disclose any competing interests.
A version of this article appeared on Medscape.com.
Inflammatory arthritis codes increased 30-fold in the transition from the ninth to the 10th revision of the International Classification of Diseases (ICD-9 and -10), yet few were used in clinical practice, according to new research.
Most of the new codes for inflammatory arthritis in ICD-10 were rarely used, if at all, from 2015 to 2021.
“About 10-20 codes were comprising the majority of usage for inflammatory arthritis patients in ICD-10,” first author Justin Zhu, a researcher and medical student at Yale University in New Haven, Connecticut, told this news organization. “The other 380 or 400 codes just weren’t seeing a lot of use.”
The findings show the difficulties of transitioning to a new system, he added, and emphasize the need for additional training to improve adoption of ICD-11. The new coding system launched globally in January 2022, but it is not clear when it will be implemented in the United States.
ICD-10 was launched in the United States in 2015, with the goal of enabling greater specificity in identifying health conditions. For example, the new coding system allowed users to include information on laterality and anatomic location for the first time. The total number of codes increased from 14,500 with ICD-9 to 70,000 with ICD-10, with the number of inflammatory arthritis diagnosis codes growing from 14 to 425.
To see how these ICD-10 codes were utilized compared with ICD-9, Zhu and colleagues used national multi-insurance administrative claims data to find inflammatory arthritis diagnostic codes for over 5.1 million patients. About half were coded in ICD-9, while the remaining half were coded in ICD-10. Mr. Zhu and colleagues defined “higher-usage codes” as those that were used more than 1% of the time.
The findings were published in a research letter in JAMA Network Open on April 18.
For ICD-9, four of the available 14 codes (28.6%) were higher-usage codes. In contrast, only nine of the 425 ICD-10 codes (2.1%) were frequently used. Though ICD-10 allowed for increased granularity in diagnosis, data showed that nonspecific codes were most popular. Of the 20 most used ICD-10 arthritis codes, 65% contained “unspecified or other specified” in its wording.
The researchers also found that there was no significant change in these higher-usage codes throughout the study period from 2015 to 2021, suggesting there was not a detectable learning curve in ICD-10 usage among physicians and coders. They also found that clinician specialty did not change code usage patterns.
“The percentage of codes used was not better for rheumatologists (who might be expected to be more refined users of such codes) than primary care clinicians,” Mr. Zhu and colleagues wrote.
Moving to ICD-11 Brings Challenges as Well as Opportunities
Mr. Zhu noted that the study highlights the challenges of adopting new technological systems into daily practice, which can inform the eventual transition to ICD-11.
“There is this need to emphasize training as well as just invest more in improving adoption of ICD-11,” he said.
Michael Pine, MD, MBA, of MJP Healthcare Innovations, LLC in Evanston, Illinois, added that ICD-11 needs to be more user-friendly to be useful in practice. While ICD-10 allowed for greater granularity in coding, it did not result in “usable granularity, in terms of the things doctors really want to communicate,” he told this news organization.
And the transition to ICD-11 could pose greater challenges; rather than ICD-10’s taxonomy system, ICD-11 is formatted as an ontology.
“Although ICD-11 retains some precoordinated codes that convey multifaceted compound concepts, its structure and syntax also provide for post-coordination, a new feature to the ICD that supports the customized combination of concepts and modifier codes to capture previously inaccessible clinical nuance,” he wrote in a coauthored invited commentary.
This added clinical nuance, however, will potentially make coding more complex, he said. One solution is to automate coding, such that clinicians could input information in a natural clinical format that makes sense to them, which would then be translated into ICD-11 code by a program. (This would then be translated back to the user in the natural clinical format to ensure accuracy.)
This type of process would limit how much any one person would need to know about ICD-11 to code diagnoses effectively, while also taking full advantage of the increasing specificity of the new coding system, he said.
Such a program does not yet exist but could be possible with intensive investment in the transition to ICD-11.
The findings of this study serve as a cautionary tale for future transitions to new systems without considering the importance of user experience and usability, Dr. Pine noted. If the United States takes an approach for the adoption of ICD-11 that is similar to that used for ICD-10, it is likely to be “just another overhyped transition” that will make users unwilling to adopt any new system moving forward out of frustration.
But if the United States takes a different, innovative approach, the opposite could be true.
“In short, the US must decide whether it is time to invest considerable resources and effort into a 21st-century information system that could overcome such hindrances as asymmetric information for decision-making, faulty risk adjustment in performance evaluations and payment formulas, and burdens imposed by current coding and documentation practices,” the commentary reads.
“It will allow us to make the best of what computers do and the best of what clinicians do,” Dr. Pine added, “and get them to work together in ways which would not have been conceivable 50 years ago.”
No information on study funding was provided. Mr. Zhu and Dr. Pine did not disclose any competing interests.
A version of this article appeared on Medscape.com.
Inflammatory arthritis codes increased 30-fold in the transition from the ninth to the 10th revision of the International Classification of Diseases (ICD-9 and -10), yet few were used in clinical practice, according to new research.
Most of the new codes for inflammatory arthritis in ICD-10 were rarely used, if at all, from 2015 to 2021.
“About 10-20 codes were comprising the majority of usage for inflammatory arthritis patients in ICD-10,” first author Justin Zhu, a researcher and medical student at Yale University in New Haven, Connecticut, told this news organization. “The other 380 or 400 codes just weren’t seeing a lot of use.”
The findings show the difficulties of transitioning to a new system, he added, and emphasize the need for additional training to improve adoption of ICD-11. The new coding system launched globally in January 2022, but it is not clear when it will be implemented in the United States.
ICD-10 was launched in the United States in 2015, with the goal of enabling greater specificity in identifying health conditions. For example, the new coding system allowed users to include information on laterality and anatomic location for the first time. The total number of codes increased from 14,500 with ICD-9 to 70,000 with ICD-10, with the number of inflammatory arthritis diagnosis codes growing from 14 to 425.
To see how these ICD-10 codes were utilized compared with ICD-9, Zhu and colleagues used national multi-insurance administrative claims data to find inflammatory arthritis diagnostic codes for over 5.1 million patients. About half were coded in ICD-9, while the remaining half were coded in ICD-10. Mr. Zhu and colleagues defined “higher-usage codes” as those that were used more than 1% of the time.
The findings were published in a research letter in JAMA Network Open on April 18.
For ICD-9, four of the available 14 codes (28.6%) were higher-usage codes. In contrast, only nine of the 425 ICD-10 codes (2.1%) were frequently used. Though ICD-10 allowed for increased granularity in diagnosis, data showed that nonspecific codes were most popular. Of the 20 most used ICD-10 arthritis codes, 65% contained “unspecified or other specified” in its wording.
The researchers also found that there was no significant change in these higher-usage codes throughout the study period from 2015 to 2021, suggesting there was not a detectable learning curve in ICD-10 usage among physicians and coders. They also found that clinician specialty did not change code usage patterns.
“The percentage of codes used was not better for rheumatologists (who might be expected to be more refined users of such codes) than primary care clinicians,” Mr. Zhu and colleagues wrote.
Moving to ICD-11 Brings Challenges as Well as Opportunities
Mr. Zhu noted that the study highlights the challenges of adopting new technological systems into daily practice, which can inform the eventual transition to ICD-11.
“There is this need to emphasize training as well as just invest more in improving adoption of ICD-11,” he said.
Michael Pine, MD, MBA, of MJP Healthcare Innovations, LLC in Evanston, Illinois, added that ICD-11 needs to be more user-friendly to be useful in practice. While ICD-10 allowed for greater granularity in coding, it did not result in “usable granularity, in terms of the things doctors really want to communicate,” he told this news organization.
And the transition to ICD-11 could pose greater challenges; rather than ICD-10’s taxonomy system, ICD-11 is formatted as an ontology.
“Although ICD-11 retains some precoordinated codes that convey multifaceted compound concepts, its structure and syntax also provide for post-coordination, a new feature to the ICD that supports the customized combination of concepts and modifier codes to capture previously inaccessible clinical nuance,” he wrote in a coauthored invited commentary.
This added clinical nuance, however, will potentially make coding more complex, he said. One solution is to automate coding, such that clinicians could input information in a natural clinical format that makes sense to them, which would then be translated into ICD-11 code by a program. (This would then be translated back to the user in the natural clinical format to ensure accuracy.)
This type of process would limit how much any one person would need to know about ICD-11 to code diagnoses effectively, while also taking full advantage of the increasing specificity of the new coding system, he said.
Such a program does not yet exist but could be possible with intensive investment in the transition to ICD-11.
The findings of this study serve as a cautionary tale for future transitions to new systems without considering the importance of user experience and usability, Dr. Pine noted. If the United States takes an approach for the adoption of ICD-11 that is similar to that used for ICD-10, it is likely to be “just another overhyped transition” that will make users unwilling to adopt any new system moving forward out of frustration.
But if the United States takes a different, innovative approach, the opposite could be true.
“In short, the US must decide whether it is time to invest considerable resources and effort into a 21st-century information system that could overcome such hindrances as asymmetric information for decision-making, faulty risk adjustment in performance evaluations and payment formulas, and burdens imposed by current coding and documentation practices,” the commentary reads.
“It will allow us to make the best of what computers do and the best of what clinicians do,” Dr. Pine added, “and get them to work together in ways which would not have been conceivable 50 years ago.”
No information on study funding was provided. Mr. Zhu and Dr. Pine did not disclose any competing interests.
A version of this article appeared on Medscape.com.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>Inflammatory arthritis codes increased 30-fold in the transition from the ninth to the 10th revision of the International Classification of Diseases (ICD-9 and </metaDescription> <articlePDF/> <teaserImage>301203</teaserImage> <teaser>Inflammatory arthritis codes increased from 14 to 425 from ICD-9 to ICD-10, yet only nine codes were commonly used in practice from 2015 to 2021.</teaser> <title>Poor Use of ICD-10 Rheumatology Codes Suggests New Approach Needed for ICD-11 Adoption</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>rn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">26</term> <term>21</term> </publications> <sections> <term canonical="true">27970</term> <term>39313</term> </sections> <topics> <term canonical="true">289</term> <term>282</term> <term>183</term> <term>299</term> <term>290</term> <term>38029</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24012895.jpg</altRep> <description role="drol:caption">Justin Zhu</description> <description role="drol:credit">Yale University</description> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24012896.jpg</altRep> <description role="drol:caption">Dr. Michael Pine</description> <description role="drol:credit"/> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Poor Use of ICD-10 Rheumatology Codes Suggests New Approach Needed for ICD-11 Adoption</title> <deck/> </itemMeta> <itemContent> <p>Inflammatory arthritis codes increased 30-fold in the transition from the ninth to the 10th revision of the International Classification of Diseases (ICD-9 and -10), yet few were used in clinical practice, according to new research.</p> <p>Most of the new codes for inflammatory arthritis in ICD-10 were rarely used, if at all, from 2015 to 2021.<br/><br/>“About 10-20 codes were comprising the majority of usage for inflammatory arthritis patients in ICD-10,” first author Justin Zhu, a researcher and medical student at Yale University in New Haven, Connecticut, told this news organization. “The other 380 or 400 codes just weren’t seeing a lot of use.”<br/><br/>[[{"fid":"301203","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Justin Zhu, a researcher and medical student at Yale University in New Haven, Connecticut","field_file_image_credit[und][0][value]":"Yale University","field_file_image_caption[und][0][value]":"Justin Zhu"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]The findings show the difficulties of transitioning to a new system, he added, and emphasize the need for additional training to improve adoption of ICD-11. The new coding system launched globally in January 2022, but it is not clear when it will be implemented in the United States.<br/><br/>ICD-10 was launched in the United States in 2015, with the goal of enabling greater specificity in identifying health conditions. For example, the new coding system allowed users to include information on laterality and anatomic location for the first time. The total number of codes increased from 14,500 with ICD-9 to 70,000 with ICD-10, with the number of inflammatory arthritis diagnosis codes growing from 14 to 425.<br/><br/>To see how these ICD-10 codes were utilized compared with ICD-9, Zhu and colleagues used national multi-insurance administrative claims data to find inflammatory arthritis diagnostic codes for over 5.1 million patients. About half were coded in ICD-9, while the remaining half were coded in ICD-10. Mr. Zhu and colleagues defined “higher-usage codes” as those that were used more than 1% of the time.<br/><br/>The findings were published in a <span class="Hyperlink"><a href="https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2817816">research letter</a></span> in <em>JAMA Network Open</em> on April 18.<br/><br/>For ICD-9, four of the available 14 codes (28.6%) were higher-usage codes. In contrast, only nine of the 425 ICD-10 codes (2.1%) were frequently used. Though ICD-10 allowed for increased granularity in diagnosis, data showed that nonspecific codes were most popular. Of the 20 most used ICD-10 arthritis codes, 65% contained “unspecified or other specified” in its wording.<br/><br/>The researchers also found that there was no significant change in these higher-usage codes throughout the study period from 2015 to 2021, suggesting there was not a detectable learning curve in ICD-10 usage among physicians and coders. They also found that clinician specialty did not change code usage patterns.<br/><br/>“The percentage of codes used was not better for rheumatologists (who might be expected to be more refined users of such codes) than primary care clinicians,” Mr. Zhu and colleagues wrote.<br/><br/></p> <h2>Moving to ICD-11 Brings Challenges as Well as Opportunities</h2> <p>Mr. Zhu noted that the study highlights the challenges of adopting new technological systems into daily practice, which can inform the eventual transition to ICD-11.</p> <p>“There is this need to emphasize training as well as just invest more in improving adoption of ICD-11,” he said.<br/><br/>Michael Pine, MD, MBA, of MJP Healthcare Innovations, LLC in Evanston, Illinois, added that ICD-11 needs to be more user-friendly to be useful in practice. While ICD-10 allowed for greater granularity in coding, it did not result in “usable granularity, in terms of the things doctors really want to communicate,” he told this news organization.<br/><br/>And the transition to ICD-11 could pose greater challenges; rather than ICD-10’s taxonomy system, ICD-11 is formatted as an ontology.[[{"fid":"301204","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Michael Pine, of MJP Healthcare Innovations, LLC in Evanston, Illinois","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"Dr. Michael Pine"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]<br/><br/>“Although ICD-11 retains some precoordinated codes that convey multifaceted compound concepts, its structure and syntax also provide for post-coordination, a new feature to the ICD that supports the customized combination of concepts and modifier codes to capture previously inaccessible clinical nuance,” he wrote in a coauthored <span class="Hyperlink"><a href="https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2817818">invited commentary</a></span>.<br/><br/>This added clinical nuance, however, will potentially make coding more complex, he said. One solution is to automate coding, such that clinicians could input information in a natural clinical format that makes sense to them, which would then be translated into ICD-11 code by a program. (This would then be translated back to the user in the natural clinical format to ensure accuracy.)<br/><br/>This type of process would limit how much any one person would need to know about ICD-11 to code diagnoses effectively, while also taking full advantage of the increasing specificity of the new coding system, he said.<br/><br/>Such a program does not yet exist but could be possible with intensive investment in the transition to ICD-11.<br/><br/>The findings of this study serve as a cautionary tale for future transitions to new systems without considering the importance of user experience and usability, Dr. Pine noted. If the United States takes an approach for the adoption of ICD-11 that is similar to that used for ICD-10, it is likely to be “just another overhyped transition” that will make users unwilling to adopt any new system moving forward out of frustration.<br/><br/>But if the United States takes a different, innovative approach, the opposite could be true.<br/><br/>“In short, the US must decide whether it is time to invest considerable resources and effort into a 21st-century information system that could overcome such hindrances as asymmetric information for decision-making, faulty risk adjustment in performance evaluations and payment formulas, and burdens imposed by current coding and documentation practices,” the commentary reads.<br/><br/>“It will allow us to make the best of what computers do and the best of what clinicians do,” Dr. Pine added, “and get them to work together in ways which would not have been conceivable 50 years ago.”<br/><br/>No information on study funding was provided. Mr. Zhu and Dr. Pine did not disclose any competing interests.<br/><br/></p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/rheumatology-data-reflect-poor-adoption-icd-10-2024a100085t?src=">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM JAMA NETWORK OPEN
The Patient Knows Best: Integrating Patient-Reported Outcomes in RA Practice and Research
Patient-reported outcomes (PROs) in rheumatology are not just personal lists of physical complaints or so-called “organ recitals.” In fact, PROs can both guide treatment decisions in daily practice and serve as key endpoints for clinical trials.
That’s the informed opinion of Clifton O. Bingham III, MD, director of the Johns Arthritis Center in Baltimore, Maryland, who discussed clinical and research applications of PROs at the 2024 Rheumatoid Arthritis Research Summit presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City.
“Integrating PROs into practice settings can enhance the clinician’s ability to understand their patients and monitor disease impact, and they are increasingly available for clinical care and are being qualified for outcome measures for clinical trials,” Dr. Bingham said.
“I posit to you that some of this ability to better characterize things like anxiety and depression levels of patients more precisely may help us to identify those patients who are less likely to respond to therapy and may require different interventions than disease-modifying therapies for their disease,” he told the audience.
PRO Examples
The term PRO encompasses a broad range of measures that may include health-related quality of life measures, symptoms and their affects, patient satisfaction, and the patient’s experience with care.
PROs are important for rheumatology care and research because “we now have the capacity to make what we used to think were the subjective experiences of disease more objective. We now have ways that we can put numbers and measurements to the experiences that patients have about their illness and use that information as a way to understand more about the patients who are in front of us and also how their disease changes over time,” Dr. Bingham said.
Patients are the best — or in some cases, the only — judges of many aspects of their health, and they are best suited to report on certain events and outcomes, he said.
PROs that are currently included in core outcome measures used to guide care and in clinical trials in pain scores as reported by visual analog scales; functioning, as measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI); and patient global assessment.
In international qualitative studies in which patients with rheumatoid arthritis (RA) were asked what was most important to them, the usual suspects of pain, function, and fatigue were routinely cited across the studies. But patients in studies from these groups (RAPP-PI, RAID, and OMERACT) also said that other factors important to their well-being included good sleep, enjoyment of life, independence, ability to participate in valued activities, and freedom from emotional distress, Dr. Bingham noted.
The Promise of PROMIS
The science of clinical measurement has advanced dramatically during his career, as Dr. Bingham said.
“There have been significant changes in the science behind how you develop and validate outcomes measures. The fields of clinimetrics and psychometrics have evolved substantially. These are now grounded in what we call ‘modern measurement’ approaches, which focus on item-response theory, constructing interval scales of measurement in things that are very precise in their ability to detect change over time,” he said.
One such measurement instrument is the Patient-Reported Outcome Measurement Information System (PROMIS®), developed at the National Institutes of Health using advanced measurement science.
The system, administered through either computer or paper questionnaires, is designed to improve precision of health-related quality of life assessments in multiple domains, including most domains identified by patients with RA. It uses a T-score metric standardized to the US population.
“You can use this in a disease like rheumatoid arthritis, and you can find out how patients are doing in reference to the normative United States populations,” he said.
Dr. Bingham noted that his team has “very good data” to show that PROMIS system significantly outperforms existing instruments such as the HAQ.
How It Works
The system uses item banks, each with multiple items. For example, there are approximately 150 items for the physical function assessment portion. All the items are scored along a continuum, “from people who are completely disabled to those who can run marathons,” Dr. Bingham said.
Each item on the scale has a question and response component, ranging from “are you able to get in and out of bed?” to “are you able to walk from one room to another?” to “are you able to run 5 miles?”
To evaluate the PROMIS scale, Dr. Bingham and colleagues looked at the distribution of PROMIS T-scores for 1029 patients with RA at their center. The scales showed that patients with RA have higher levels of pain, fatigue, and sleep disturbances, as well as worse physical function, than population norms.
Dr. Bingham and colleagues also evaluated the performance of the system in patients with active RA who were starting on or switching to a different disease-modifying antirheumatic drug (DMARD). As they reported in 2019, among 106 participants who completed the 12-week study, all PROMIS scores improved after DMARD initiation (P ≤ .05). In addition, except for the depression domain, changes in all assessed PROMIS measures correlated with changes in Clinical Disease Activity Index scores.
To see whether integrating PROs into routine clinics could have an effect on care, Dr. Bingham and colleagues conducted a prospective cohort study, which showed that with the additional patient-reported data, clinicians changed or adjusted RA treatment in 16%-19% of visits, identified new symptoms in 27%-38%, and suggested nonpharmacologic interventions in 4%-11%.
“This is information that’s being used, and it’s going into changing medical decision making,” he said.
Summarizing his work, Dr. Bingham told the audience “I hope that I have convinced you that patients with RA prioritize domains that are impacted by their disease. PROMIS measures are really state-of-the-science methods to evaluate multiple aspects of health-related quality of life, and what I’ll note to you is that these have been translated into multiple languages internationally. There are Spanish-language versions, there are Chinese language versions, there are versions for every country in the [European Union] that have been validated and can be used.”
It’s a Start
In the Q & A following the presentation, Daniel H. Solomon, MD, MPH, from Brigham and Women’s Hospital in Boston, commented that “the measurement issues and automating measurements seems like it’s a fundamental practice issue — how to manage the system and how to manage patients better, and I feel like we’re kind of scratching the surface.”
He said that artificial intelligence and PROs in clinic offer some promise for improving care but added that “we can do better than this. We can figure out better systems for measuring PROs: Having patients measure PROs, having patients tell us about their PROs so they don’t have to come in, or coming in only when they need to come in, when they’re really flaring. There are lots of innovative ways of thinking about these tools, and it feels like we’re kind of on the cusp of really taking advantage.”
Dr. Bingham’s work is supported by the Patient-Centered Outcomes Research Institute, National Institutes of Health, Ira T. Fine Discovery Fund, Johns Hopkins Arthritis Center Discovery Fund, Camille J. Morgan Arthritis Research and Education Fund, and Scheer Family Foundation and Joanne and John Rogers. He disclosed consulting for AbbVie, Janssen, Lilly, and Sanofi and serving as a board member of the PROMIS health organization, co-chair of the Omeract Technical Advisory Group, and member of the C-PATH RA PRO working group. Dr. Solomon had no relevant disclosures.
A version of this article appeared on Medscape.com.
Patient-reported outcomes (PROs) in rheumatology are not just personal lists of physical complaints or so-called “organ recitals.” In fact, PROs can both guide treatment decisions in daily practice and serve as key endpoints for clinical trials.
That’s the informed opinion of Clifton O. Bingham III, MD, director of the Johns Arthritis Center in Baltimore, Maryland, who discussed clinical and research applications of PROs at the 2024 Rheumatoid Arthritis Research Summit presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City.
“Integrating PROs into practice settings can enhance the clinician’s ability to understand their patients and monitor disease impact, and they are increasingly available for clinical care and are being qualified for outcome measures for clinical trials,” Dr. Bingham said.
“I posit to you that some of this ability to better characterize things like anxiety and depression levels of patients more precisely may help us to identify those patients who are less likely to respond to therapy and may require different interventions than disease-modifying therapies for their disease,” he told the audience.
PRO Examples
The term PRO encompasses a broad range of measures that may include health-related quality of life measures, symptoms and their affects, patient satisfaction, and the patient’s experience with care.
PROs are important for rheumatology care and research because “we now have the capacity to make what we used to think were the subjective experiences of disease more objective. We now have ways that we can put numbers and measurements to the experiences that patients have about their illness and use that information as a way to understand more about the patients who are in front of us and also how their disease changes over time,” Dr. Bingham said.
Patients are the best — or in some cases, the only — judges of many aspects of their health, and they are best suited to report on certain events and outcomes, he said.
PROs that are currently included in core outcome measures used to guide care and in clinical trials in pain scores as reported by visual analog scales; functioning, as measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI); and patient global assessment.
In international qualitative studies in which patients with rheumatoid arthritis (RA) were asked what was most important to them, the usual suspects of pain, function, and fatigue were routinely cited across the studies. But patients in studies from these groups (RAPP-PI, RAID, and OMERACT) also said that other factors important to their well-being included good sleep, enjoyment of life, independence, ability to participate in valued activities, and freedom from emotional distress, Dr. Bingham noted.
The Promise of PROMIS
The science of clinical measurement has advanced dramatically during his career, as Dr. Bingham said.
“There have been significant changes in the science behind how you develop and validate outcomes measures. The fields of clinimetrics and psychometrics have evolved substantially. These are now grounded in what we call ‘modern measurement’ approaches, which focus on item-response theory, constructing interval scales of measurement in things that are very precise in their ability to detect change over time,” he said.
One such measurement instrument is the Patient-Reported Outcome Measurement Information System (PROMIS®), developed at the National Institutes of Health using advanced measurement science.
The system, administered through either computer or paper questionnaires, is designed to improve precision of health-related quality of life assessments in multiple domains, including most domains identified by patients with RA. It uses a T-score metric standardized to the US population.
“You can use this in a disease like rheumatoid arthritis, and you can find out how patients are doing in reference to the normative United States populations,” he said.
Dr. Bingham noted that his team has “very good data” to show that PROMIS system significantly outperforms existing instruments such as the HAQ.
How It Works
The system uses item banks, each with multiple items. For example, there are approximately 150 items for the physical function assessment portion. All the items are scored along a continuum, “from people who are completely disabled to those who can run marathons,” Dr. Bingham said.
Each item on the scale has a question and response component, ranging from “are you able to get in and out of bed?” to “are you able to walk from one room to another?” to “are you able to run 5 miles?”
To evaluate the PROMIS scale, Dr. Bingham and colleagues looked at the distribution of PROMIS T-scores for 1029 patients with RA at their center. The scales showed that patients with RA have higher levels of pain, fatigue, and sleep disturbances, as well as worse physical function, than population norms.
Dr. Bingham and colleagues also evaluated the performance of the system in patients with active RA who were starting on or switching to a different disease-modifying antirheumatic drug (DMARD). As they reported in 2019, among 106 participants who completed the 12-week study, all PROMIS scores improved after DMARD initiation (P ≤ .05). In addition, except for the depression domain, changes in all assessed PROMIS measures correlated with changes in Clinical Disease Activity Index scores.
To see whether integrating PROs into routine clinics could have an effect on care, Dr. Bingham and colleagues conducted a prospective cohort study, which showed that with the additional patient-reported data, clinicians changed or adjusted RA treatment in 16%-19% of visits, identified new symptoms in 27%-38%, and suggested nonpharmacologic interventions in 4%-11%.
“This is information that’s being used, and it’s going into changing medical decision making,” he said.
Summarizing his work, Dr. Bingham told the audience “I hope that I have convinced you that patients with RA prioritize domains that are impacted by their disease. PROMIS measures are really state-of-the-science methods to evaluate multiple aspects of health-related quality of life, and what I’ll note to you is that these have been translated into multiple languages internationally. There are Spanish-language versions, there are Chinese language versions, there are versions for every country in the [European Union] that have been validated and can be used.”
It’s a Start
In the Q & A following the presentation, Daniel H. Solomon, MD, MPH, from Brigham and Women’s Hospital in Boston, commented that “the measurement issues and automating measurements seems like it’s a fundamental practice issue — how to manage the system and how to manage patients better, and I feel like we’re kind of scratching the surface.”
He said that artificial intelligence and PROs in clinic offer some promise for improving care but added that “we can do better than this. We can figure out better systems for measuring PROs: Having patients measure PROs, having patients tell us about their PROs so they don’t have to come in, or coming in only when they need to come in, when they’re really flaring. There are lots of innovative ways of thinking about these tools, and it feels like we’re kind of on the cusp of really taking advantage.”
Dr. Bingham’s work is supported by the Patient-Centered Outcomes Research Institute, National Institutes of Health, Ira T. Fine Discovery Fund, Johns Hopkins Arthritis Center Discovery Fund, Camille J. Morgan Arthritis Research and Education Fund, and Scheer Family Foundation and Joanne and John Rogers. He disclosed consulting for AbbVie, Janssen, Lilly, and Sanofi and serving as a board member of the PROMIS health organization, co-chair of the Omeract Technical Advisory Group, and member of the C-PATH RA PRO working group. Dr. Solomon had no relevant disclosures.
A version of this article appeared on Medscape.com.
Patient-reported outcomes (PROs) in rheumatology are not just personal lists of physical complaints or so-called “organ recitals.” In fact, PROs can both guide treatment decisions in daily practice and serve as key endpoints for clinical trials.
That’s the informed opinion of Clifton O. Bingham III, MD, director of the Johns Arthritis Center in Baltimore, Maryland, who discussed clinical and research applications of PROs at the 2024 Rheumatoid Arthritis Research Summit presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City.
“Integrating PROs into practice settings can enhance the clinician’s ability to understand their patients and monitor disease impact, and they are increasingly available for clinical care and are being qualified for outcome measures for clinical trials,” Dr. Bingham said.
“I posit to you that some of this ability to better characterize things like anxiety and depression levels of patients more precisely may help us to identify those patients who are less likely to respond to therapy and may require different interventions than disease-modifying therapies for their disease,” he told the audience.
PRO Examples
The term PRO encompasses a broad range of measures that may include health-related quality of life measures, symptoms and their affects, patient satisfaction, and the patient’s experience with care.
PROs are important for rheumatology care and research because “we now have the capacity to make what we used to think were the subjective experiences of disease more objective. We now have ways that we can put numbers and measurements to the experiences that patients have about their illness and use that information as a way to understand more about the patients who are in front of us and also how their disease changes over time,” Dr. Bingham said.
Patients are the best — or in some cases, the only — judges of many aspects of their health, and they are best suited to report on certain events and outcomes, he said.
PROs that are currently included in core outcome measures used to guide care and in clinical trials in pain scores as reported by visual analog scales; functioning, as measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI); and patient global assessment.
In international qualitative studies in which patients with rheumatoid arthritis (RA) were asked what was most important to them, the usual suspects of pain, function, and fatigue were routinely cited across the studies. But patients in studies from these groups (RAPP-PI, RAID, and OMERACT) also said that other factors important to their well-being included good sleep, enjoyment of life, independence, ability to participate in valued activities, and freedom from emotional distress, Dr. Bingham noted.
The Promise of PROMIS
The science of clinical measurement has advanced dramatically during his career, as Dr. Bingham said.
“There have been significant changes in the science behind how you develop and validate outcomes measures. The fields of clinimetrics and psychometrics have evolved substantially. These are now grounded in what we call ‘modern measurement’ approaches, which focus on item-response theory, constructing interval scales of measurement in things that are very precise in their ability to detect change over time,” he said.
One such measurement instrument is the Patient-Reported Outcome Measurement Information System (PROMIS®), developed at the National Institutes of Health using advanced measurement science.
The system, administered through either computer or paper questionnaires, is designed to improve precision of health-related quality of life assessments in multiple domains, including most domains identified by patients with RA. It uses a T-score metric standardized to the US population.
“You can use this in a disease like rheumatoid arthritis, and you can find out how patients are doing in reference to the normative United States populations,” he said.
Dr. Bingham noted that his team has “very good data” to show that PROMIS system significantly outperforms existing instruments such as the HAQ.
How It Works
The system uses item banks, each with multiple items. For example, there are approximately 150 items for the physical function assessment portion. All the items are scored along a continuum, “from people who are completely disabled to those who can run marathons,” Dr. Bingham said.
Each item on the scale has a question and response component, ranging from “are you able to get in and out of bed?” to “are you able to walk from one room to another?” to “are you able to run 5 miles?”
To evaluate the PROMIS scale, Dr. Bingham and colleagues looked at the distribution of PROMIS T-scores for 1029 patients with RA at their center. The scales showed that patients with RA have higher levels of pain, fatigue, and sleep disturbances, as well as worse physical function, than population norms.
Dr. Bingham and colleagues also evaluated the performance of the system in patients with active RA who were starting on or switching to a different disease-modifying antirheumatic drug (DMARD). As they reported in 2019, among 106 participants who completed the 12-week study, all PROMIS scores improved after DMARD initiation (P ≤ .05). In addition, except for the depression domain, changes in all assessed PROMIS measures correlated with changes in Clinical Disease Activity Index scores.
To see whether integrating PROs into routine clinics could have an effect on care, Dr. Bingham and colleagues conducted a prospective cohort study, which showed that with the additional patient-reported data, clinicians changed or adjusted RA treatment in 16%-19% of visits, identified new symptoms in 27%-38%, and suggested nonpharmacologic interventions in 4%-11%.
“This is information that’s being used, and it’s going into changing medical decision making,” he said.
Summarizing his work, Dr. Bingham told the audience “I hope that I have convinced you that patients with RA prioritize domains that are impacted by their disease. PROMIS measures are really state-of-the-science methods to evaluate multiple aspects of health-related quality of life, and what I’ll note to you is that these have been translated into multiple languages internationally. There are Spanish-language versions, there are Chinese language versions, there are versions for every country in the [European Union] that have been validated and can be used.”
It’s a Start
In the Q & A following the presentation, Daniel H. Solomon, MD, MPH, from Brigham and Women’s Hospital in Boston, commented that “the measurement issues and automating measurements seems like it’s a fundamental practice issue — how to manage the system and how to manage patients better, and I feel like we’re kind of scratching the surface.”
He said that artificial intelligence and PROs in clinic offer some promise for improving care but added that “we can do better than this. We can figure out better systems for measuring PROs: Having patients measure PROs, having patients tell us about their PROs so they don’t have to come in, or coming in only when they need to come in, when they’re really flaring. There are lots of innovative ways of thinking about these tools, and it feels like we’re kind of on the cusp of really taking advantage.”
Dr. Bingham’s work is supported by the Patient-Centered Outcomes Research Institute, National Institutes of Health, Ira T. Fine Discovery Fund, Johns Hopkins Arthritis Center Discovery Fund, Camille J. Morgan Arthritis Research and Education Fund, and Scheer Family Foundation and Joanne and John Rogers. He disclosed consulting for AbbVie, Janssen, Lilly, and Sanofi and serving as a board member of the PROMIS health organization, co-chair of the Omeract Technical Advisory Group, and member of the C-PATH RA PRO working group. Dr. Solomon had no relevant disclosures.
A version of this article appeared on Medscape.com.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>Patient-reported outcomes (PROs) in rheumatology are not just personal lists of physical complaints or so-called “organ recitals.” In fact, PROs can both guide </metaDescription> <articlePDF/> <teaserImage>301134</teaserImage> <teaser>Advanced systems for measuring patient-reported outcomes can help to improve care of patients with rheumatoid arthritis and inform clinical research.</teaser> <title>The Patient Knows Best: Integrating Patient-Reported Outcomes in RA Practice and Research</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>rn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">26</term> <term>21</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term canonical="true">289</term> <term>290</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24012844.jpg</altRep> <description role="drol:caption">Dr. Clifton O. Bingham III</description> <description role="drol:credit">Johns Hopkins Medicine, Johns Hopkins Division of Rheumatology</description> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>The Patient Knows Best: Integrating Patient-Reported Outcomes in RA Practice and Research</title> <deck/> </itemMeta> <itemContent> <p>Patient-reported outcomes (PROs) in rheumatology are not just personal lists of physical complaints or so-called “organ recitals.” In fact, PROs can both guide treatment decisions in daily practice and serve as key endpoints for clinical trials.</p> <p>That’s the informed opinion of Clifton O. Bingham III, MD, director of the Johns Arthritis Center in Baltimore, Maryland, who discussed clinical and research applications of PROs at the <span class="Hyperlink"><a href="https://www.medscape.com/viewcollection/37505">2024 Rheumatoid Arthritis Research Summit</a></span> presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City.<br/><br/>[[{"fid":"301134","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. Clifton O. Bingham III, director of the Johns Hopkins Arthritis Center in Baltimore, Maryland","field_file_image_credit[und][0][value]":"Johns Hopkins Medicine, Johns Hopkins Division of Rheumatology","field_file_image_caption[und][0][value]":"Dr. Clifton O. Bingham III"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]“Integrating PROs into practice settings can enhance the clinician’s ability to understand their patients and monitor disease impact, and they are increasingly available for clinical care and are being qualified for outcome measures for clinical trials,” Dr. Bingham said.<br/><br/>“I posit to you that some of this ability to better characterize things like anxiety and <span class="Hyperlink"><a href="https://emedicine.medscape.com/article/286759-overview">depression</a></span> levels of patients more precisely may help us to identify those patients who are less likely to respond to therapy and may require different interventions than disease-modifying therapies for their disease,” he told the audience.<br/><br/></p> <h2>PRO Examples</h2> <p>The term PRO encompasses a broad range of measures that may include health-related quality of life measures, symptoms and their affects, patient satisfaction, and the patient’s experience with care.</p> <p>PROs are important for rheumatology care and research because “we now have the capacity to make what we used to think were the subjective experiences of disease more objective. We now have ways that we can put numbers and measurements to the experiences that patients have about their illness and use that information as a way to understand more about the patients who are in front of us and also how their disease changes over time,” Dr. Bingham said.<br/><br/>Patients are the best — or in some cases, the only — judges of many aspects of their health, and they are best suited to report on certain events and outcomes, he said.<br/><br/>PROs that are currently included in core outcome measures used to guide care and in clinical trials in pain scores as reported by visual analog scales; functioning, as measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI); and patient global assessment.<br/><br/>In international qualitative studies in which patients with rheumatoid arthritis (RA) were asked what was most important to them, the usual suspects of pain, function, and fatigue were routinely cited across the studies. But patients in studies from these groups (<span class="Hyperlink"><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2886964/">RAPP-PI</a></span>, <span class="Hyperlink"><a href="https://ard.bmj.com/content/68/11/1680.long">RAID</a></span>, and <span class="Hyperlink"><a href="https://ard.bmj.com/content/71/11/1855.long">OMERACT</a></span>) also said that other factors important to their well-being included good sleep, enjoyment of life, independence, ability to participate in valued activities, and freedom from emotional distress, Dr. Bingham noted.<br/><br/></p> <h2>The Promise of PROMIS</h2> <p>The science of clinical measurement has advanced dramatically during his career, as Dr. Bingham said.</p> <p>“There have been significant changes in the science behind how you develop and validate outcomes measures. The fields of clinimetrics and psychometrics have evolved substantially. These are now grounded in what we call ‘modern measurement’ approaches, which focus on item-response theory, constructing interval scales of measurement in things that are very precise in their ability to detect change over time,” he said.<br/><br/>One such measurement instrument is the Patient-Reported Outcome Measurement Information System (PROMIS®), developed at the National Institutes of Health using advanced measurement science.<br/><br/>The system, administered through either computer or paper questionnaires, is designed to improve precision of health-related quality of life assessments in multiple domains, including most domains identified by patients with RA. It uses a T-score metric standardized to the US population.<br/><br/>“You can use this in a disease like rheumatoid arthritis, and you can find out how patients are doing in reference to the normative United States populations,” he said.<br/><br/>Dr. Bingham noted that his team has “very good data” to show that PROMIS system significantly outperforms existing instruments such as the HAQ.<br/><br/></p> <h2>How It Works</h2> <p>The system uses item banks, each with multiple items. For example, there are approximately 150 items for the physical function assessment portion. All the items are scored along a continuum, “from people who are completely disabled to those who can run marathons,” Dr. Bingham said.</p> <p>Each item on the scale has a question and response component, ranging from “are you able to get in and out of bed?” to “are you able to walk from one room to another?” to “are you able to run 5 miles?”<br/><br/>To evaluate the PROMIS scale, Dr. Bingham and colleagues looked at the distribution of PROMIS T-scores for 1029 patients with RA at their center. The scales showed that patients with RA have higher levels of pain, fatigue, and sleep disturbances, as well as worse physical function, than population norms.<br/><br/>Dr. Bingham and colleagues also evaluated the performance of the system in patients with active RA who were starting on or switching to a different disease-modifying antirheumatic drug (DMARD). As they <span class="Hyperlink"><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286688/">reported in 2019</a></span>, among 106 participants who completed the 12-week study, all PROMIS scores improved after DMARD initiation (<em>P</em> ≤ .05). In addition, except for the depression domain, changes in all assessed PROMIS measures correlated with changes in Clinical Disease Activity Index scores.<br/><br/>To see whether integrating PROs into routine clinics could have an effect on care, Dr. Bingham and colleagues conducted a <span class="Hyperlink"><a href="https://academic.oup.com/rheumatology/article/59/7/1662/5610168?login=false">prospective cohort study</a></span>, which showed that with the additional patient-reported data, clinicians changed or adjusted RA treatment in 16%-19% of visits, identified new symptoms in 27%-38%, and suggested nonpharmacologic interventions in 4%-11%.<br/><br/>“This is information that’s being used, and it’s going into changing medical decision making,” he said.<br/><br/>Summarizing his work, Dr. Bingham told the audience “I hope that I have convinced you that patients with RA prioritize domains that are impacted by their disease. PROMIS measures are really state-of-the-science methods to evaluate multiple aspects of health-related quality of life, and what I’ll note to you is that these have been translated into multiple languages internationally. There are Spanish-language versions, there are Chinese language versions, there are versions for every country in the [European Union] that have been validated and can be used.”<br/><br/></p> <h2>It’s a Start</h2> <p>In the Q & A following the presentation, Daniel H. Solomon, MD, MPH, from Brigham and Women’s Hospital in Boston, commented that “the measurement issues and automating measurements seems like it’s a fundamental practice issue — how to manage the system and how to manage patients better, and I feel like we’re kind of scratching the surface.”</p> <p>He said that artificial intelligence and PROs in clinic offer some promise for improving care but added that “we can do better than this. We can figure out better systems for measuring PROs: Having patients measure PROs, having patients tell us about their PROs so they don’t have to come in, or coming in only when they need to come in, when they’re really flaring. There are lots of innovative ways of thinking about these tools, and it feels like we’re kind of on the cusp of really taking advantage.”<br/><br/>Dr. Bingham’s work is supported by the Patient-Centered Outcomes Research Institute, National Institutes of Health, Ira T. Fine Discovery Fund, Johns Hopkins Arthritis Center Discovery Fund, Camille J. Morgan Arthritis Research and Education Fund, and Scheer Family Foundation and Joanne and John Rogers. He disclosed consulting for AbbVie, Janssen, Lilly, and Sanofi and serving as a board member of the PROMIS health organization, co-chair of the Omeract Technical Advisory Group, and member of the C-PATH RA PRO working group. Dr. Solomon had no relevant disclosures.<span class="end"/></p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/patient-knows-best-pros-ra-practice-and-research-2024a10007n3?src=">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM RA SUMMIT 2024
Mining EHRs with AI to Predict RA Outcomes: Coming to You Soon?
Rheumatologists and their staff have been dutifully recording disease activity and patient-reported outcomes for decades, and now, all that drudgery is beginning to pay off with the introduction of artificial intelligence (AI) and natural language processing systems that can mine electronic health records (EHRs) for nuggets of research gold and accurately predict short-term rheumatoid arthritis (RA) outcomes.
“I think we have learned from our very early experiments that longitudinal deep learning models can forecast rheumatoid arthritis [RA] outcomes with actually surprising efficiency, with fewer patients than we assumed would be needed,” said Jinoos Yazdany, MD, MPH, chief of rheumatology at Zuckerberg San Francisco General Hospital and Trauma Center, and codirector of the University of California San Francisco (UCSF) Quality and Informatics Lab.
At the 2024 Rheumatoid Arthritis Research Summit (RA Summit 2024), presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City, Dr. Yazdany discussed why rheumatologists are well positioned to take advantage of predictive analytics and how natural language processing systems can be used to extract previously hard-to-find data from EHRs, which can then be applied to RA prognostics and research.
Data Galore
EHR data can be particularly useful for RA research because of the large volume of information, clinical data such as notes and imaging, less selection bias compared with other data sources such as cohorts or randomized controlled trials, real-time access, and the fact that many records contain longitudinal data (follow-ups, etc.).
However, EHR data may have gaps or inaccurate coding, and data such as text and images may require significant data processing and scrubbing before it can be used to advance research. In addition, EHR data are subject to patient privacy and security concerns, can be plagued by incompatibility across different systems, and may not represent patients who have less access to care, Dr. Yazdany said.
She noted that most rheumatologists record some measure of RA disease activity and patient physical function, and that patient-reported outcomes have been routinely incorporated into clinical records, especially since the 1980 introduction of the Health Assessment Questionnaire.
“In rheumatology, by achieving consensus and building a national quality measurement program, we have a cohesive national RA outcome measure selection strategy. RA outcomes are available for a majority of patients seen by rheumatologists, and that’s a critical strength of EHR data,” she said.
Spinning Text Into Analytics
The challenge for investigators who want to use this treasure trove of RA data is that more than 80% of the data are in the form of text, which raises questions about how to best extract outcomes data and drug dosing information from the written record.
As described in an article published online in Arthritis Care & Research February 14, 2023, Dr. Yazdany and colleagues at UCSF and Stanford University developed a natural language processing “pipeline” designed to extract RA outcomes from clinical notes on all patients included in the American College of Rheumatology’s Rheumatology Informatics System for Effectiveness (RISE) registry.
The model used expert-curated terms and a text processing tool to identify patterns and numerical scores linked to outcome measures in the records.
“This was an enormously difficult and ambitious project because we had many, many sites, the data was very messy, we had very complicated [independent review board] procedures, and we actually had to go through de-identification procedures because we were using this data for research, so we learned a lot,” Dr. Yazdany said.
The model processed 34 million notes on 854,628 patients across 158 practices and 24 different EHR systems.
In internal validation studies, the models had 95% sensitivity, 87% positive predictive value (PPV), and an F1 score (a measure of predictive performance) of 91%. Applying the model to an EHR from a large, non-RISE health system for external validation, the natural language processing pipeline had a 92% sensitivity, 69% PPV, and an F1 score of 79%.
The investigators also looked at the use of OpenAI large language models, including GPT 3.5 and 4 to interpret complex prescription orders and found that after training with 100 examples, GPT 4 was able to correctly interpret 95.6% of orders. But this experiment came at a high computational and financial cost, with one experiment running north of $3000, Dr. Yazdany cautioned.
Predicting Outcomes
Experiments to see whether an AI system can forecast RA disease activity at the next clinic visit are in their early stages.
Dr. Yazdany and colleagues used EHR data from UCSF and Zuckerberg San Francisco General Hospital on patients with two RA diagnostic codes at 30 days apart, who had at least one disease-modifying antirheumatic drug prescription and two Clinical Disease Activity Index (CDAI) scores 30 days apart.
One model, designed to predict CDAI at the next visit by “playing the odds” based on clinical experience, showed that about 60% of patients at UCSF achieved treat-to-target goals, while the remaining 40% did not.
This model performed barely better than pure chance, with an area under the receiver operating characteristic curve (AUC) of 0.54.
A second model that included the patient’s last CDAI score also fared little better than a roll of the dice, with an AUC of 0.55.
However, a neural network or “deep learning” model designed to process data akin to the way that the human brain works performed much better at predicting outcomes at the second visit, with an AUC of 0.91.
Applying the UCSF-trained neural network model to the Zuckerberg San Francisco General Hospital population, with different patient characteristics from those of UCSF, the AUC was 0.74. Although this result was not as good as that seen when applied to UCSF patients, it demonstrated that the model retains some predictive capability across different hospital systems, Dr. Yazdany said.
The next steps, she said, are to build more robust models based on vast and varied patient data pools that will allow the predictive models to be generalized across various healthcare settings.
The Here and Now
In the Q & A following the presentation, an audience member said that the study was “very cool stuff.”
“Is there a way to sort of get ahead and think of the technology that we’re starting to pilot? Hospitals are already using AI scribes, for example, to collect the data that is going to make it much easier to feed it to the predictive analytics that we’re going to use,” she said.
Dr. Yazdany replied that “over the last couple of years, one of the projects that we’ve worked on is to interview rheumatologists who are participating in the RISE registry about the ways that they are collecting [patient-reported outcomes], and it has been fascinating: A vast majority of people are still using paper forms.”
“The challenge is that our patient populations are very diverse. Technology, and especially filling out forms via online platforms, doesn’t work for everybody, and in some ways, filling out the paper forms when you go to the doctor’s office is a great equalizer. So, I think that we have some real challenges, and the solutions have to be embedded in the real world,” she added.
Dr. Yazdany’s research was supported by grants from the Agency for Healthcare Research & Quality and the National Institutes of Health. She disclosed consulting fees and/or research support from AstraZeneca, Aurinia, Bristol Myers Squibb, Gilead, and Pfizer.
A version of this article appeared on Medscape.com.
Rheumatologists and their staff have been dutifully recording disease activity and patient-reported outcomes for decades, and now, all that drudgery is beginning to pay off with the introduction of artificial intelligence (AI) and natural language processing systems that can mine electronic health records (EHRs) for nuggets of research gold and accurately predict short-term rheumatoid arthritis (RA) outcomes.
“I think we have learned from our very early experiments that longitudinal deep learning models can forecast rheumatoid arthritis [RA] outcomes with actually surprising efficiency, with fewer patients than we assumed would be needed,” said Jinoos Yazdany, MD, MPH, chief of rheumatology at Zuckerberg San Francisco General Hospital and Trauma Center, and codirector of the University of California San Francisco (UCSF) Quality and Informatics Lab.
At the 2024 Rheumatoid Arthritis Research Summit (RA Summit 2024), presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City, Dr. Yazdany discussed why rheumatologists are well positioned to take advantage of predictive analytics and how natural language processing systems can be used to extract previously hard-to-find data from EHRs, which can then be applied to RA prognostics and research.
Data Galore
EHR data can be particularly useful for RA research because of the large volume of information, clinical data such as notes and imaging, less selection bias compared with other data sources such as cohorts or randomized controlled trials, real-time access, and the fact that many records contain longitudinal data (follow-ups, etc.).
However, EHR data may have gaps or inaccurate coding, and data such as text and images may require significant data processing and scrubbing before it can be used to advance research. In addition, EHR data are subject to patient privacy and security concerns, can be plagued by incompatibility across different systems, and may not represent patients who have less access to care, Dr. Yazdany said.
She noted that most rheumatologists record some measure of RA disease activity and patient physical function, and that patient-reported outcomes have been routinely incorporated into clinical records, especially since the 1980 introduction of the Health Assessment Questionnaire.
“In rheumatology, by achieving consensus and building a national quality measurement program, we have a cohesive national RA outcome measure selection strategy. RA outcomes are available for a majority of patients seen by rheumatologists, and that’s a critical strength of EHR data,” she said.
Spinning Text Into Analytics
The challenge for investigators who want to use this treasure trove of RA data is that more than 80% of the data are in the form of text, which raises questions about how to best extract outcomes data and drug dosing information from the written record.
As described in an article published online in Arthritis Care & Research February 14, 2023, Dr. Yazdany and colleagues at UCSF and Stanford University developed a natural language processing “pipeline” designed to extract RA outcomes from clinical notes on all patients included in the American College of Rheumatology’s Rheumatology Informatics System for Effectiveness (RISE) registry.
The model used expert-curated terms and a text processing tool to identify patterns and numerical scores linked to outcome measures in the records.
“This was an enormously difficult and ambitious project because we had many, many sites, the data was very messy, we had very complicated [independent review board] procedures, and we actually had to go through de-identification procedures because we were using this data for research, so we learned a lot,” Dr. Yazdany said.
The model processed 34 million notes on 854,628 patients across 158 practices and 24 different EHR systems.
In internal validation studies, the models had 95% sensitivity, 87% positive predictive value (PPV), and an F1 score (a measure of predictive performance) of 91%. Applying the model to an EHR from a large, non-RISE health system for external validation, the natural language processing pipeline had a 92% sensitivity, 69% PPV, and an F1 score of 79%.
The investigators also looked at the use of OpenAI large language models, including GPT 3.5 and 4 to interpret complex prescription orders and found that after training with 100 examples, GPT 4 was able to correctly interpret 95.6% of orders. But this experiment came at a high computational and financial cost, with one experiment running north of $3000, Dr. Yazdany cautioned.
Predicting Outcomes
Experiments to see whether an AI system can forecast RA disease activity at the next clinic visit are in their early stages.
Dr. Yazdany and colleagues used EHR data from UCSF and Zuckerberg San Francisco General Hospital on patients with two RA diagnostic codes at 30 days apart, who had at least one disease-modifying antirheumatic drug prescription and two Clinical Disease Activity Index (CDAI) scores 30 days apart.
One model, designed to predict CDAI at the next visit by “playing the odds” based on clinical experience, showed that about 60% of patients at UCSF achieved treat-to-target goals, while the remaining 40% did not.
This model performed barely better than pure chance, with an area under the receiver operating characteristic curve (AUC) of 0.54.
A second model that included the patient’s last CDAI score also fared little better than a roll of the dice, with an AUC of 0.55.
However, a neural network or “deep learning” model designed to process data akin to the way that the human brain works performed much better at predicting outcomes at the second visit, with an AUC of 0.91.
Applying the UCSF-trained neural network model to the Zuckerberg San Francisco General Hospital population, with different patient characteristics from those of UCSF, the AUC was 0.74. Although this result was not as good as that seen when applied to UCSF patients, it demonstrated that the model retains some predictive capability across different hospital systems, Dr. Yazdany said.
The next steps, she said, are to build more robust models based on vast and varied patient data pools that will allow the predictive models to be generalized across various healthcare settings.
The Here and Now
In the Q & A following the presentation, an audience member said that the study was “very cool stuff.”
“Is there a way to sort of get ahead and think of the technology that we’re starting to pilot? Hospitals are already using AI scribes, for example, to collect the data that is going to make it much easier to feed it to the predictive analytics that we’re going to use,” she said.
Dr. Yazdany replied that “over the last couple of years, one of the projects that we’ve worked on is to interview rheumatologists who are participating in the RISE registry about the ways that they are collecting [patient-reported outcomes], and it has been fascinating: A vast majority of people are still using paper forms.”
“The challenge is that our patient populations are very diverse. Technology, and especially filling out forms via online platforms, doesn’t work for everybody, and in some ways, filling out the paper forms when you go to the doctor’s office is a great equalizer. So, I think that we have some real challenges, and the solutions have to be embedded in the real world,” she added.
Dr. Yazdany’s research was supported by grants from the Agency for Healthcare Research & Quality and the National Institutes of Health. She disclosed consulting fees and/or research support from AstraZeneca, Aurinia, Bristol Myers Squibb, Gilead, and Pfizer.
A version of this article appeared on Medscape.com.
Rheumatologists and their staff have been dutifully recording disease activity and patient-reported outcomes for decades, and now, all that drudgery is beginning to pay off with the introduction of artificial intelligence (AI) and natural language processing systems that can mine electronic health records (EHRs) for nuggets of research gold and accurately predict short-term rheumatoid arthritis (RA) outcomes.
“I think we have learned from our very early experiments that longitudinal deep learning models can forecast rheumatoid arthritis [RA] outcomes with actually surprising efficiency, with fewer patients than we assumed would be needed,” said Jinoos Yazdany, MD, MPH, chief of rheumatology at Zuckerberg San Francisco General Hospital and Trauma Center, and codirector of the University of California San Francisco (UCSF) Quality and Informatics Lab.
At the 2024 Rheumatoid Arthritis Research Summit (RA Summit 2024), presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City, Dr. Yazdany discussed why rheumatologists are well positioned to take advantage of predictive analytics and how natural language processing systems can be used to extract previously hard-to-find data from EHRs, which can then be applied to RA prognostics and research.
Data Galore
EHR data can be particularly useful for RA research because of the large volume of information, clinical data such as notes and imaging, less selection bias compared with other data sources such as cohorts or randomized controlled trials, real-time access, and the fact that many records contain longitudinal data (follow-ups, etc.).
However, EHR data may have gaps or inaccurate coding, and data such as text and images may require significant data processing and scrubbing before it can be used to advance research. In addition, EHR data are subject to patient privacy and security concerns, can be plagued by incompatibility across different systems, and may not represent patients who have less access to care, Dr. Yazdany said.
She noted that most rheumatologists record some measure of RA disease activity and patient physical function, and that patient-reported outcomes have been routinely incorporated into clinical records, especially since the 1980 introduction of the Health Assessment Questionnaire.
“In rheumatology, by achieving consensus and building a national quality measurement program, we have a cohesive national RA outcome measure selection strategy. RA outcomes are available for a majority of patients seen by rheumatologists, and that’s a critical strength of EHR data,” she said.
Spinning Text Into Analytics
The challenge for investigators who want to use this treasure trove of RA data is that more than 80% of the data are in the form of text, which raises questions about how to best extract outcomes data and drug dosing information from the written record.
As described in an article published online in Arthritis Care & Research February 14, 2023, Dr. Yazdany and colleagues at UCSF and Stanford University developed a natural language processing “pipeline” designed to extract RA outcomes from clinical notes on all patients included in the American College of Rheumatology’s Rheumatology Informatics System for Effectiveness (RISE) registry.
The model used expert-curated terms and a text processing tool to identify patterns and numerical scores linked to outcome measures in the records.
“This was an enormously difficult and ambitious project because we had many, many sites, the data was very messy, we had very complicated [independent review board] procedures, and we actually had to go through de-identification procedures because we were using this data for research, so we learned a lot,” Dr. Yazdany said.
The model processed 34 million notes on 854,628 patients across 158 practices and 24 different EHR systems.
In internal validation studies, the models had 95% sensitivity, 87% positive predictive value (PPV), and an F1 score (a measure of predictive performance) of 91%. Applying the model to an EHR from a large, non-RISE health system for external validation, the natural language processing pipeline had a 92% sensitivity, 69% PPV, and an F1 score of 79%.
The investigators also looked at the use of OpenAI large language models, including GPT 3.5 and 4 to interpret complex prescription orders and found that after training with 100 examples, GPT 4 was able to correctly interpret 95.6% of orders. But this experiment came at a high computational and financial cost, with one experiment running north of $3000, Dr. Yazdany cautioned.
Predicting Outcomes
Experiments to see whether an AI system can forecast RA disease activity at the next clinic visit are in their early stages.
Dr. Yazdany and colleagues used EHR data from UCSF and Zuckerberg San Francisco General Hospital on patients with two RA diagnostic codes at 30 days apart, who had at least one disease-modifying antirheumatic drug prescription and two Clinical Disease Activity Index (CDAI) scores 30 days apart.
One model, designed to predict CDAI at the next visit by “playing the odds” based on clinical experience, showed that about 60% of patients at UCSF achieved treat-to-target goals, while the remaining 40% did not.
This model performed barely better than pure chance, with an area under the receiver operating characteristic curve (AUC) of 0.54.
A second model that included the patient’s last CDAI score also fared little better than a roll of the dice, with an AUC of 0.55.
However, a neural network or “deep learning” model designed to process data akin to the way that the human brain works performed much better at predicting outcomes at the second visit, with an AUC of 0.91.
Applying the UCSF-trained neural network model to the Zuckerberg San Francisco General Hospital population, with different patient characteristics from those of UCSF, the AUC was 0.74. Although this result was not as good as that seen when applied to UCSF patients, it demonstrated that the model retains some predictive capability across different hospital systems, Dr. Yazdany said.
The next steps, she said, are to build more robust models based on vast and varied patient data pools that will allow the predictive models to be generalized across various healthcare settings.
The Here and Now
In the Q & A following the presentation, an audience member said that the study was “very cool stuff.”
“Is there a way to sort of get ahead and think of the technology that we’re starting to pilot? Hospitals are already using AI scribes, for example, to collect the data that is going to make it much easier to feed it to the predictive analytics that we’re going to use,” she said.
Dr. Yazdany replied that “over the last couple of years, one of the projects that we’ve worked on is to interview rheumatologists who are participating in the RISE registry about the ways that they are collecting [patient-reported outcomes], and it has been fascinating: A vast majority of people are still using paper forms.”
“The challenge is that our patient populations are very diverse. Technology, and especially filling out forms via online platforms, doesn’t work for everybody, and in some ways, filling out the paper forms when you go to the doctor’s office is a great equalizer. So, I think that we have some real challenges, and the solutions have to be embedded in the real world,” she added.
Dr. Yazdany’s research was supported by grants from the Agency for Healthcare Research & Quality and the National Institutes of Health. She disclosed consulting fees and/or research support from AstraZeneca, Aurinia, Bristol Myers Squibb, Gilead, and Pfizer.
A version of this article appeared on Medscape.com.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>Rheumatologists and their staff have been dutifully recording disease activity and patient-reported outcomes for decades, and now, all that drudgery is beginnin</metaDescription> <articlePDF/> <teaserImage>257886</teaserImage> <teaser>Plugging massive amounts of data from EHRs into AI systems may turn masses of silicon chips into crystal balls foretelling treatment efficacy.</teaser> <title>Mining EHRs with AI to Predict RA Outcomes: Coming to You Soon?</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>rn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">26</term> <term>21</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term canonical="true">289</term> <term>290</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/2400d7e1.jpg</altRep> <description role="drol:caption">Dr. Jinoos Yazdany</description> <description role="drol:credit"/> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Mining EHRs with AI to Predict RA Outcomes: Coming to You Soon?</title> <deck/> </itemMeta> <itemContent> <p>Rheumatologists and their staff have been dutifully recording disease activity and patient-reported outcomes for decades, and now, all that drudgery is beginning to pay off with the introduction of artificial intelligence (AI) and natural language processing systems that can mine electronic health records (EHRs) for nuggets of research gold and accurately predict short-term rheumatoid arthritis (RA) outcomes.</p> <p>“I think we have learned from our very early experiments that longitudinal deep learning models can forecast rheumatoid arthritis [RA] outcomes with actually surprising efficiency, with fewer patients than we assumed would be needed,” said Jinoos Yazdany, MD, MPH, chief of rheumatology at Zuckerberg San Francisco General Hospital and Trauma Center, and codirector of the University of California San Francisco (UCSF) Quality and Informatics Lab.<br/><br/>[[{"fid":"257886","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. Jinoos Yazdany, chief of rheumatology at Zuckerberg San Francisco General Hospital and Trauma Center","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"Dr. Jinoos Yazdany"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]At the <span class="Hyperlink"><a href="https://www.medscape.com/viewcollection/37505">2024 Rheumatoid Arthritis Research Summit (RA Summit 2024)</a></span>, presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City, Dr. Yazdany discussed why rheumatologists are well positioned to take advantage of predictive analytics and how natural language processing systems can be used to extract previously hard-to-find data from EHRs, which can then be applied to RA prognostics and research.<br/><br/></p> <h2>Data Galore</h2> <p>EHR data can be particularly useful for RA research because of the large volume of information, clinical data such as notes and imaging, less selection bias compared with other data sources such as cohorts or randomized controlled trials, real-time access, and the fact that many records contain longitudinal data (follow-ups, etc.).</p> <p>However, EHR data may have gaps or inaccurate coding, and data such as text and images may require significant data processing and scrubbing before it can be used to advance research. In addition, EHR data are subject to patient privacy and security concerns, can be plagued by incompatibility across different systems, and may not represent patients who have less access to care, Dr. Yazdany said.<br/><br/>She noted that most rheumatologists record some measure of RA disease activity and patient physical function, and that patient-reported outcomes have been routinely incorporated into clinical records, especially since the 1980 introduction of the Health Assessment Questionnaire.<br/><br/>“In rheumatology, by achieving consensus and building a national quality measurement program, we have a cohesive national RA outcome measure selection strategy. RA outcomes are available for a majority of patients seen by rheumatologists, and that’s a critical strength of EHR data,” she said.<br/><br/></p> <h2>Spinning Text Into Analytics</h2> <p>The challenge for investigators who want to use this treasure trove of RA data is that more than 80% of the data are in the form of text, which raises questions about how to best extract outcomes data and drug dosing information from the written record.<br/><br/>As described in an <span class="Hyperlink"><a href="https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/acr.24869">article published</a> online</span> in <em>Arthritis Care & Research</em> February 14, 2023, Dr. Yazdany and colleagues at UCSF and Stanford University developed a natural language processing “pipeline” designed to extract RA outcomes from clinical notes on all patients included in the American College of Rheumatology’s Rheumatology Informatics System for Effectiveness (RISE) registry.<br/><br/>The model used expert-curated terms and a text processing tool to identify patterns and numerical scores linked to outcome measures in the records.<br/><br/>“This was an enormously difficult and ambitious project because we had many, many sites, the data was very messy, we had very complicated [independent review board] procedures, and we actually had to go through de-identification procedures because we were using this data for research, so we learned a lot,” Dr. Yazdany said.<br/><br/>The model processed 34 million notes on 854,628 patients across 158 practices and 24 different EHR systems.<br/><br/>In internal validation studies, the models had 95% sensitivity, 87% positive predictive value (PPV), and an F1 score (a measure of predictive performance) of 91%. Applying the model to an EHR from a large, non-RISE health system for external validation, the natural language processing pipeline had a 92% sensitivity, 69% PPV, and an F1 score of 79%.<br/><br/>The investigators also looked at the use of OpenAI large language models, including GPT 3.5 and 4 to interpret complex prescription orders and found that after training with 100 examples, GPT 4 was able to correctly interpret 95.6% of orders. But this experiment came at a high computational and financial cost, with one experiment running north of $3000, Dr. Yazdany cautioned.<br/><br/></p> <h2>Predicting Outcomes</h2> <p>Experiments to see whether an AI system can forecast RA disease activity at the next clinic visit are in their early stages.<br/><br/><span class="Hyperlink">Dr. <a href="https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2728001">Yazdany and colleagues</a></span> used EHR data from UCSF and Zuckerberg San Francisco General Hospital on patients with two RA diagnostic codes at 30 days apart, who had at least one disease-modifying antirheumatic drug prescription and two Clinical Disease Activity Index (CDAI) scores 30 days apart.<br/><br/>One model, designed to predict CDAI at the next visit by “playing the odds” based on clinical experience, showed that about 60% of patients at UCSF achieved treat-to-target goals, while the remaining 40% did not.<br/><br/>This model performed barely better than pure chance, with an area under the receiver operating characteristic curve (AUC) of 0.54.<br/><br/>A second model that included the patient’s last CDAI score also fared little better than a roll of the dice, with an AUC of 0.55.<br/><br/>However, a neural network or “deep learning” model designed to process data akin to the way that the human brain works performed much better at predicting outcomes at the second visit, with an AUC of 0.91.<br/><br/>Applying the UCSF-trained neural network model to the Zuckerberg San Francisco General Hospital population, with different patient characteristics from those of UCSF, the AUC was 0.74. Although this result was not as good as that seen when applied to UCSF patients, it demonstrated that the model retains some predictive capability across different hospital systems, Dr. Yazdany said.<br/><br/>The next steps, she said, are to build more robust models based on vast and varied patient data pools that will allow the predictive models to be generalized across various healthcare settings.<br/><br/></p> <h2>The Here and Now</h2> <p>In the Q & A following the presentation, an audience member said that the study was “very cool stuff.”</p> <p>“Is there a way to sort of get ahead and think of the technology that we’re starting to pilot? Hospitals are already using AI scribes, for example, to collect the data that is going to make it much easier to feed it to the predictive analytics that we’re going to use,” she said.<br/><br/>Dr. Yazdany replied that “over the last couple of years, one of the projects that we’ve worked on is to interview rheumatologists who are participating in the RISE registry about the ways that they are collecting [patient-reported outcomes], and it has been fascinating: A vast majority of people are still using paper forms.”<br/><br/>“The challenge is that our patient populations are very diverse. Technology, and especially filling out forms via online platforms, doesn’t work for everybody, and in some ways, filling out the paper forms when you go to the doctor’s office is a great equalizer. So, I think that we have some real challenges, and the solutions have to be embedded in the real world,” she added.<br/><br/>Dr. Yazdany’s research was supported by grants from the Agency for Healthcare Research & Quality and the National Institutes of Health. She disclosed consulting fees and/or research support from AstraZeneca, Aurinia, Bristol Myers Squibb, Gilead, and Pfizer.</p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/investigators-train-ai-systems-predict-ra-outcomes-2024a10007ke?src=">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM RA SUMMIT 2024
Shared Rheumatology-Primary Care Telehealth Model Brings Services to Rural Areas
Even in large urban areas there aren’t enough rheumatologists to go around, and as a 2015 American College of Rheumatology workforce study projected, the number of rheumatology providers is expected to drop by 25% by the year 2030, while the demand for patient care in rheumatology is expected to increase by more than 100%.
The shortage of rheumatology care is even more acute in rural areas, but as a pilot project supported by the Arthritis Foundation shows, linking rheumatologists to health centers in remote and underserved locations via telehealth can help community providers improve care for patients with rheumatic diseases.
The novel collaborative model was described by Alfredo Rivadeneira, MD, professor of medicine in the division of rheumatology, allergy, and immunology at the University of North Carolina (UNC) School of Medicine in Chapel Hill, North Carolina.
“We found that this pilot, a unique partnership in North Carolina, improves access to rheumatology care to a rural population with high satisfaction scores. It underlines the importance of seeking collaboration with community providers when implementing these programs. It also allows timely specialty care and alleviates the barriers relating to transportation, insurance coverage, and telecommunication challenges,” he said at the 2024 Rheumatoid Arthritis Research Summit presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City.
Too Many Patients, Too Few Rheumatologists
Access to health is challenging for people from traditionally underserved racial and ethnic backgrounds, especially in states such as North Carolina, where 40% of the population lives in rural counties, which have higher age-adjusted mortality than more densely populated areas of the state, Dr. Rivadeneira said.
In addition, 42% of the North Carolina residents seen at the state’s 42 Federally Qualified Health Centers (FQHCs) don’t have health insurance, which is higher than the average of 23% uninsured seen at FQHCs in other states.
There are currently approximately 250 rheumatology providers in North Carolina, the majority of whom work in the states’ three academic medical centers. Currently, North Carolina has an estimated population of 10 million people, which is projected to increase to 11.7 million by 2030. And by 2030, 20% of North Carolinians will be aged ≥ 65 years, Dr. Rivadeneira said, highlighting the need for expanded rheumatology care.
Although telehealth services could be an option for expanding services to underserved communities, only 14 of the 42 FQHCs in the state use telehealth and only on a limited basis because it is not sufficiently reimbursed.
Rivadeneira pointed to a 2022 study that showed how patients with rheumatic and musculoskeletal disease patients in North Carolina were less likely to use online patient portals if they lived in rural areas; came from racial or ethnic minority backgrounds; were older, men, had lower economic status (Medicaid enrollment or uninsured); or spoke a language other than English as their primary tongue.
Pilot Project
To help smooth out some of the above-mentioned disparities, Dr. Rivadeneira and colleagues, in collaboration with the Arthritis Foundation, started a pilot project in 2022 designed to enhance access to rheumatology specialty care for rural residents through a shared telehealth model between the UNC rheumatology clinic and two separate Piedmont Health Services clinics in rural areas.
The project includes tailored educational sessions designed to empower Piedmont Health Services providers for evaluating and managing patients with rheumatic diseases.
Patients with prior diagnoses of rheumatologic diseases who were lost to rheumatology specialty care follow-up and those with new rheumatic symptoms who had transportation and/or financial barriers to receiving specialty care are triaged to the shared telemedicine visits.
Providers conduct monthly clinic sessions via shared visits between the on-site Piedmont Health Services provider and patients, with off-site UNC rheumatology fellows and attending physicians connected virtually.
The educational component of the project includes monthly didactic sessions offered to all Piedmont Health Services providers across 12 locations.
The topics that were chosen cover the most common rheumatologic conditions seen by community providers, including evaluating pain from a rheumatology perspective; using antinuclear antibodies and other serologies; evaluating and managing rheumatoid arthritis, lupus, gout, giant cell arteritis, polymyalgia rheumatica, and osteoarthritis; and methotrexate management and complications.
“One of the aspects of this pilot that I want to emphasize is the importance of having the generalists with the patient, relaying the objective data, especially the physical exam, and that’s one of the great features of this model. It also provides a stable platform for telehealth to the individual patients, as many of these patients don’t have access to health technology,” Dr. Rivadeneira said.
Thumbs Up
Both patients and general practitioners in the Piedmont Health system expressed high degrees of satisfaction with the shared telehealth program. Patients especially liked the time they saved not having to travel to see a specialist, and a large majority agreed that the visits were “as good as” in-person visits, felt that their concerns were addressed appropriately during the virtual visit, expressed overall satisfaction, and said they would like to continue virtual visits.
Physicians expressed a high degree of satisfaction with the rheumatology didactic sessions and said that the sessions enhanced their knowledge of evaluating and managing or co-managing rheumatologic diseases, as well as helping them to feel comfortable about applying this knowledge to patient care.
Dr. Rivadeneira noted that the pilot study was limited by low levels of Piedmont Health Services physician participation (two out of 45 total participated in shared visits), and only three or four providers typically took part in each didactic session.
How to Improve?
In a follow-up study, the investigators asked Piedmont Health Services providers about barriers to rheumatology care, the most common and challenging diseases they encountered, how to improve the didactic components, and their perspectives on the pilot and how it may have affected referral patterns to rheumatology care.
The providers identified the cost of diagnostic evaluations and medications, transportation, long wait times, and language as the main barriers to patient access of rheumatology care.
“Additionally, over a third of them encountered patients on a weekly basis that were overdue for a visit with a rheumatologist,” Dr. Rivadeneira said.
“Direct participation in the physical exam by the primary care provider enhances greatly, in my opinion, these telehealth visits. Focused didactic sessions, electronic handouts and/or quick access guides could empower more rural community providers to manage rheumatic diseases,” he concluded.
In the Q&A following the presentation, Laura Cappelli, MD, MHS, MS, associate professor of medicine in the division of rheumatology at Johns Hopkins School of Medicine in Baltimore, asked Dr. Rivadeneira how rheumatologists involved felt about the program and whether his team did any surveying or qualitative work with them.
“Just so you know, the rheumatologist was me,” he replied.
“I’m very picky about telemedicine,” he continued. “I don’t like it, I prefer, as most of us do, to have the patient there. But having the provider there, doing the exam, and you guiding them — I can ask, ‘Did you check their joints? Did you check their strength?’ — makes a huge difference and makes me feel comfortable with the sessions.”
Dr. Rivadeneira added that if a particular case was too complex or too vague to adequately assess via telehealth, he would arrange to see the patient in person.
The project was supported by the Arthritis Foundation. Dr. Rivadeneira and Dr. Cappelli reported no conflicts of interest.
A version of this article appeared on Medscape.com.
Even in large urban areas there aren’t enough rheumatologists to go around, and as a 2015 American College of Rheumatology workforce study projected, the number of rheumatology providers is expected to drop by 25% by the year 2030, while the demand for patient care in rheumatology is expected to increase by more than 100%.
The shortage of rheumatology care is even more acute in rural areas, but as a pilot project supported by the Arthritis Foundation shows, linking rheumatologists to health centers in remote and underserved locations via telehealth can help community providers improve care for patients with rheumatic diseases.
The novel collaborative model was described by Alfredo Rivadeneira, MD, professor of medicine in the division of rheumatology, allergy, and immunology at the University of North Carolina (UNC) School of Medicine in Chapel Hill, North Carolina.
“We found that this pilot, a unique partnership in North Carolina, improves access to rheumatology care to a rural population with high satisfaction scores. It underlines the importance of seeking collaboration with community providers when implementing these programs. It also allows timely specialty care and alleviates the barriers relating to transportation, insurance coverage, and telecommunication challenges,” he said at the 2024 Rheumatoid Arthritis Research Summit presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City.
Too Many Patients, Too Few Rheumatologists
Access to health is challenging for people from traditionally underserved racial and ethnic backgrounds, especially in states such as North Carolina, where 40% of the population lives in rural counties, which have higher age-adjusted mortality than more densely populated areas of the state, Dr. Rivadeneira said.
In addition, 42% of the North Carolina residents seen at the state’s 42 Federally Qualified Health Centers (FQHCs) don’t have health insurance, which is higher than the average of 23% uninsured seen at FQHCs in other states.
There are currently approximately 250 rheumatology providers in North Carolina, the majority of whom work in the states’ three academic medical centers. Currently, North Carolina has an estimated population of 10 million people, which is projected to increase to 11.7 million by 2030. And by 2030, 20% of North Carolinians will be aged ≥ 65 years, Dr. Rivadeneira said, highlighting the need for expanded rheumatology care.
Although telehealth services could be an option for expanding services to underserved communities, only 14 of the 42 FQHCs in the state use telehealth and only on a limited basis because it is not sufficiently reimbursed.
Rivadeneira pointed to a 2022 study that showed how patients with rheumatic and musculoskeletal disease patients in North Carolina were less likely to use online patient portals if they lived in rural areas; came from racial or ethnic minority backgrounds; were older, men, had lower economic status (Medicaid enrollment or uninsured); or spoke a language other than English as their primary tongue.
Pilot Project
To help smooth out some of the above-mentioned disparities, Dr. Rivadeneira and colleagues, in collaboration with the Arthritis Foundation, started a pilot project in 2022 designed to enhance access to rheumatology specialty care for rural residents through a shared telehealth model between the UNC rheumatology clinic and two separate Piedmont Health Services clinics in rural areas.
The project includes tailored educational sessions designed to empower Piedmont Health Services providers for evaluating and managing patients with rheumatic diseases.
Patients with prior diagnoses of rheumatologic diseases who were lost to rheumatology specialty care follow-up and those with new rheumatic symptoms who had transportation and/or financial barriers to receiving specialty care are triaged to the shared telemedicine visits.
Providers conduct monthly clinic sessions via shared visits between the on-site Piedmont Health Services provider and patients, with off-site UNC rheumatology fellows and attending physicians connected virtually.
The educational component of the project includes monthly didactic sessions offered to all Piedmont Health Services providers across 12 locations.
The topics that were chosen cover the most common rheumatologic conditions seen by community providers, including evaluating pain from a rheumatology perspective; using antinuclear antibodies and other serologies; evaluating and managing rheumatoid arthritis, lupus, gout, giant cell arteritis, polymyalgia rheumatica, and osteoarthritis; and methotrexate management and complications.
“One of the aspects of this pilot that I want to emphasize is the importance of having the generalists with the patient, relaying the objective data, especially the physical exam, and that’s one of the great features of this model. It also provides a stable platform for telehealth to the individual patients, as many of these patients don’t have access to health technology,” Dr. Rivadeneira said.
Thumbs Up
Both patients and general practitioners in the Piedmont Health system expressed high degrees of satisfaction with the shared telehealth program. Patients especially liked the time they saved not having to travel to see a specialist, and a large majority agreed that the visits were “as good as” in-person visits, felt that their concerns were addressed appropriately during the virtual visit, expressed overall satisfaction, and said they would like to continue virtual visits.
Physicians expressed a high degree of satisfaction with the rheumatology didactic sessions and said that the sessions enhanced their knowledge of evaluating and managing or co-managing rheumatologic diseases, as well as helping them to feel comfortable about applying this knowledge to patient care.
Dr. Rivadeneira noted that the pilot study was limited by low levels of Piedmont Health Services physician participation (two out of 45 total participated in shared visits), and only three or four providers typically took part in each didactic session.
How to Improve?
In a follow-up study, the investigators asked Piedmont Health Services providers about barriers to rheumatology care, the most common and challenging diseases they encountered, how to improve the didactic components, and their perspectives on the pilot and how it may have affected referral patterns to rheumatology care.
The providers identified the cost of diagnostic evaluations and medications, transportation, long wait times, and language as the main barriers to patient access of rheumatology care.
“Additionally, over a third of them encountered patients on a weekly basis that were overdue for a visit with a rheumatologist,” Dr. Rivadeneira said.
“Direct participation in the physical exam by the primary care provider enhances greatly, in my opinion, these telehealth visits. Focused didactic sessions, electronic handouts and/or quick access guides could empower more rural community providers to manage rheumatic diseases,” he concluded.
In the Q&A following the presentation, Laura Cappelli, MD, MHS, MS, associate professor of medicine in the division of rheumatology at Johns Hopkins School of Medicine in Baltimore, asked Dr. Rivadeneira how rheumatologists involved felt about the program and whether his team did any surveying or qualitative work with them.
“Just so you know, the rheumatologist was me,” he replied.
“I’m very picky about telemedicine,” he continued. “I don’t like it, I prefer, as most of us do, to have the patient there. But having the provider there, doing the exam, and you guiding them — I can ask, ‘Did you check their joints? Did you check their strength?’ — makes a huge difference and makes me feel comfortable with the sessions.”
Dr. Rivadeneira added that if a particular case was too complex or too vague to adequately assess via telehealth, he would arrange to see the patient in person.
The project was supported by the Arthritis Foundation. Dr. Rivadeneira and Dr. Cappelli reported no conflicts of interest.
A version of this article appeared on Medscape.com.
Even in large urban areas there aren’t enough rheumatologists to go around, and as a 2015 American College of Rheumatology workforce study projected, the number of rheumatology providers is expected to drop by 25% by the year 2030, while the demand for patient care in rheumatology is expected to increase by more than 100%.
The shortage of rheumatology care is even more acute in rural areas, but as a pilot project supported by the Arthritis Foundation shows, linking rheumatologists to health centers in remote and underserved locations via telehealth can help community providers improve care for patients with rheumatic diseases.
The novel collaborative model was described by Alfredo Rivadeneira, MD, professor of medicine in the division of rheumatology, allergy, and immunology at the University of North Carolina (UNC) School of Medicine in Chapel Hill, North Carolina.
“We found that this pilot, a unique partnership in North Carolina, improves access to rheumatology care to a rural population with high satisfaction scores. It underlines the importance of seeking collaboration with community providers when implementing these programs. It also allows timely specialty care and alleviates the barriers relating to transportation, insurance coverage, and telecommunication challenges,” he said at the 2024 Rheumatoid Arthritis Research Summit presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City.
Too Many Patients, Too Few Rheumatologists
Access to health is challenging for people from traditionally underserved racial and ethnic backgrounds, especially in states such as North Carolina, where 40% of the population lives in rural counties, which have higher age-adjusted mortality than more densely populated areas of the state, Dr. Rivadeneira said.
In addition, 42% of the North Carolina residents seen at the state’s 42 Federally Qualified Health Centers (FQHCs) don’t have health insurance, which is higher than the average of 23% uninsured seen at FQHCs in other states.
There are currently approximately 250 rheumatology providers in North Carolina, the majority of whom work in the states’ three academic medical centers. Currently, North Carolina has an estimated population of 10 million people, which is projected to increase to 11.7 million by 2030. And by 2030, 20% of North Carolinians will be aged ≥ 65 years, Dr. Rivadeneira said, highlighting the need for expanded rheumatology care.
Although telehealth services could be an option for expanding services to underserved communities, only 14 of the 42 FQHCs in the state use telehealth and only on a limited basis because it is not sufficiently reimbursed.
Rivadeneira pointed to a 2022 study that showed how patients with rheumatic and musculoskeletal disease patients in North Carolina were less likely to use online patient portals if they lived in rural areas; came from racial or ethnic minority backgrounds; were older, men, had lower economic status (Medicaid enrollment or uninsured); or spoke a language other than English as their primary tongue.
Pilot Project
To help smooth out some of the above-mentioned disparities, Dr. Rivadeneira and colleagues, in collaboration with the Arthritis Foundation, started a pilot project in 2022 designed to enhance access to rheumatology specialty care for rural residents through a shared telehealth model between the UNC rheumatology clinic and two separate Piedmont Health Services clinics in rural areas.
The project includes tailored educational sessions designed to empower Piedmont Health Services providers for evaluating and managing patients with rheumatic diseases.
Patients with prior diagnoses of rheumatologic diseases who were lost to rheumatology specialty care follow-up and those with new rheumatic symptoms who had transportation and/or financial barriers to receiving specialty care are triaged to the shared telemedicine visits.
Providers conduct monthly clinic sessions via shared visits between the on-site Piedmont Health Services provider and patients, with off-site UNC rheumatology fellows and attending physicians connected virtually.
The educational component of the project includes monthly didactic sessions offered to all Piedmont Health Services providers across 12 locations.
The topics that were chosen cover the most common rheumatologic conditions seen by community providers, including evaluating pain from a rheumatology perspective; using antinuclear antibodies and other serologies; evaluating and managing rheumatoid arthritis, lupus, gout, giant cell arteritis, polymyalgia rheumatica, and osteoarthritis; and methotrexate management and complications.
“One of the aspects of this pilot that I want to emphasize is the importance of having the generalists with the patient, relaying the objective data, especially the physical exam, and that’s one of the great features of this model. It also provides a stable platform for telehealth to the individual patients, as many of these patients don’t have access to health technology,” Dr. Rivadeneira said.
Thumbs Up
Both patients and general practitioners in the Piedmont Health system expressed high degrees of satisfaction with the shared telehealth program. Patients especially liked the time they saved not having to travel to see a specialist, and a large majority agreed that the visits were “as good as” in-person visits, felt that their concerns were addressed appropriately during the virtual visit, expressed overall satisfaction, and said they would like to continue virtual visits.
Physicians expressed a high degree of satisfaction with the rheumatology didactic sessions and said that the sessions enhanced their knowledge of evaluating and managing or co-managing rheumatologic diseases, as well as helping them to feel comfortable about applying this knowledge to patient care.
Dr. Rivadeneira noted that the pilot study was limited by low levels of Piedmont Health Services physician participation (two out of 45 total participated in shared visits), and only three or four providers typically took part in each didactic session.
How to Improve?
In a follow-up study, the investigators asked Piedmont Health Services providers about barriers to rheumatology care, the most common and challenging diseases they encountered, how to improve the didactic components, and their perspectives on the pilot and how it may have affected referral patterns to rheumatology care.
The providers identified the cost of diagnostic evaluations and medications, transportation, long wait times, and language as the main barriers to patient access of rheumatology care.
“Additionally, over a third of them encountered patients on a weekly basis that were overdue for a visit with a rheumatologist,” Dr. Rivadeneira said.
“Direct participation in the physical exam by the primary care provider enhances greatly, in my opinion, these telehealth visits. Focused didactic sessions, electronic handouts and/or quick access guides could empower more rural community providers to manage rheumatic diseases,” he concluded.
In the Q&A following the presentation, Laura Cappelli, MD, MHS, MS, associate professor of medicine in the division of rheumatology at Johns Hopkins School of Medicine in Baltimore, asked Dr. Rivadeneira how rheumatologists involved felt about the program and whether his team did any surveying or qualitative work with them.
“Just so you know, the rheumatologist was me,” he replied.
“I’m very picky about telemedicine,” he continued. “I don’t like it, I prefer, as most of us do, to have the patient there. But having the provider there, doing the exam, and you guiding them — I can ask, ‘Did you check their joints? Did you check their strength?’ — makes a huge difference and makes me feel comfortable with the sessions.”
Dr. Rivadeneira added that if a particular case was too complex or too vague to adequately assess via telehealth, he would arrange to see the patient in person.
The project was supported by the Arthritis Foundation. Dr. Rivadeneira and Dr. Cappelli reported no conflicts of interest.
A version of this article appeared on Medscape.com.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>Even in large urban areas there aren’t enough rheumatologists to go around, and as a 2015 American College of Rheumatology workforce study projected, the number</metaDescription> <articlePDF/> <teaserImage>301139</teaserImage> <teaser>Patients with rheumatic diseases who live in underserved areas may benefit from virtual visits conducted jointly by rheumatologists and PCPs trained in recognizing and managing these conditions.</teaser> <title>Shared Rheumatology-Primary Care Telehealth Model Brings Services to Rural Areas</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>rn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">26</term> <term>21</term> <term>15</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term canonical="true">38029</term> <term>289</term> <term>290</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/2401284e.jpg</altRep> <description role="drol:caption">Dr. Alfredo Rivadeneira</description> <description role="drol:credit">UNC School of Medicine</description> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Shared Rheumatology-Primary Care Telehealth Model Brings Services to Rural Areas</title> <deck/> </itemMeta> <itemContent> <p>Even in large urban areas there aren’t enough rheumatologists to go around, and as a 2015 American College of Rheumatology workforce study projected, the number of rheumatology providers is expected to drop by 25% by the year 2030, while the demand for patient care in rheumatology is expected to increase by more than 100%.</p> <p>The shortage of rheumatology care is even more acute in rural areas, but as a pilot project supported by the Arthritis Foundation shows, linking rheumatologists to health centers in remote and underserved locations via telehealth can help community providers improve care for patients with rheumatic diseases.<br/><br/>The novel collaborative model was described by Alfredo Rivadeneira, MD, professor of medicine in the division of rheumatology, allergy, and immunology at the University of North Carolina (UNC) School of Medicine in Chapel Hill, North Carolina.<br/><br/>[[{"fid":"301139","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. Alfredo Rivadeneira, professor of medicine in the division of rheumatology, allergy, and immunology at the University of North Carolina (UNC) School of Medicine in Chapel Hill, North Carolina","field_file_image_credit[und][0][value]":"UNC School of Medicine","field_file_image_caption[und][0][value]":"Dr. Alfredo Rivadeneira"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]“We found that this pilot, a unique partnership in North Carolina, improves access to rheumatology care to a rural population with high satisfaction scores. It underlines the importance of seeking collaboration with community providers when implementing these programs. It also allows timely specialty care and alleviates the barriers relating to transportation, insurance coverage, and telecommunication challenges,” he said at the 2024 <span class="Hyperlink">Rheumatoid Arthritis</span> Research Summit presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City. <br/><br/></p> <h2>Too Many Patients, Too Few Rheumatologists</h2> <p>Access to health is challenging for people from traditionally underserved racial and ethnic backgrounds, especially in states such as North Carolina, where 40% of the population lives in rural counties, which have higher age-adjusted mortality than more densely populated areas of the state, Dr. Rivadeneira said. </p> <p>In addition, 42% of the North Carolina residents seen at the state’s 42 Federally Qualified Health Centers (FQHCs) don’t have health insurance, which is higher than the average of 23% uninsured seen at FQHCs in other states.<br/><br/>There are currently approximately 250 rheumatology providers in North Carolina, the majority of whom work in the states’ three academic medical centers. Currently, North Carolina has an estimated population of 10 million people, which is projected to increase to 11.7 million by 2030. And by 2030, 20% of North Carolinians will be aged ≥ 65 years, Dr. Rivadeneira said, highlighting the need for expanded rheumatology care. <br/><br/>Although telehealth services could be an option for expanding services to underserved communities, only 14 of the 42 FQHCs in the state use telehealth and only on a limited basis because it is not sufficiently reimbursed. <br/><br/>Rivadeneira pointed to a <span class="Hyperlink"><a href="https://www.jmir.org/2022/8/e38802">2022 study</a></span> that showed how patients with rheumatic and musculoskeletal disease patients in North Carolina were less likely to use online patient portals if they lived in rural areas; came from racial or ethnic minority backgrounds; were older, men, had lower economic status (Medicaid enrollment or uninsured); or spoke a language other than English as their primary tongue. <br/><br/></p> <h2>Pilot Project</h2> <p>To help smooth out some of the above-mentioned disparities, Dr. Rivadeneira and colleagues, in collaboration with the Arthritis Foundation, started a pilot project in 2022 designed to enhance access to rheumatology specialty care for rural residents through a shared telehealth model between the UNC rheumatology clinic and two separate Piedmont Health Services clinics in rural areas.</p> <p>The project includes tailored educational sessions designed to empower Piedmont Health Services providers for evaluating and managing patients with rheumatic diseases.<br/><br/>Patients with prior diagnoses of rheumatologic diseases who were lost to rheumatology specialty care follow-up and those with new rheumatic symptoms who had transportation and/or financial barriers to receiving specialty care are triaged to the shared telemedicine visits.<br/><br/>Providers conduct monthly clinic sessions via shared visits between the on-site Piedmont Health Services provider and patients, with off-site UNC rheumatology fellows and attending physicians connected virtually. <br/><br/>The educational component of the project includes monthly didactic sessions offered to all Piedmont Health Services providers across 12 locations. <br/><br/>The topics that were chosen cover the most common rheumatologic conditions seen by community providers, including evaluating pain from a rheumatology perspective; using antinuclear antibodies and other serologies; evaluating and managing rheumatoid arthritis, lupus, <span class="Hyperlink">gout</span>, <span class="Hyperlink">giant cell arteritis</span>, <span class="Hyperlink">polymyalgia rheumatica</span>, and <span class="Hyperlink">osteoarthritis</span>; and <span class="Hyperlink">methotrexate</span> management and complications. <br/><br/>“One of the aspects of this pilot that I want to emphasize is the importance of having the generalists with the patient, relaying the objective data, especially the physical exam, and that’s one of the great features of this model. It also provides a stable platform for telehealth to the individual patients, as many of these patients don’t have access to health technology,” Dr. Rivadeneira said. <br/><br/></p> <h2>Thumbs Up</h2> <p>Both patients and general practitioners in the Piedmont Health system expressed high degrees of satisfaction with the shared telehealth program. Patients especially liked the time they saved not having to travel to see a specialist, and a large majority agreed that the visits were “as good as” in-person visits, felt that their concerns were addressed appropriately during the virtual visit, expressed overall satisfaction, and said they would like to continue virtual visits.</p> <p>Physicians expressed a high degree of satisfaction with the rheumatology didactic sessions and said that the sessions enhanced their knowledge of evaluating and managing or co-managing rheumatologic diseases, as well as helping them to feel comfortable about applying this knowledge to patient care.<br/><br/>Dr. Rivadeneira noted that the pilot study was limited by low levels of Piedmont Health Services physician participation (two out of 45 total participated in shared visits), and only three or four providers typically took part in each didactic session. <br/><br/></p> <h2>How to Improve?</h2> <p>In a follow-up study, the investigators asked Piedmont Health Services providers about barriers to rheumatology care, the most common and challenging diseases they encountered, how to improve the didactic components, and their perspectives on the pilot and how it may have affected referral patterns to rheumatology care.</p> <p>The providers identified the cost of diagnostic evaluations and medications, transportation, long wait times, and language as the main barriers to patient access of rheumatology care.<br/><br/>“Additionally, over a third of them encountered patients on a weekly basis that were overdue for a visit with a rheumatologist,” Dr. Rivadeneira said. <br/><br/>“Direct participation in the physical exam by the primary care provider enhances greatly, in my opinion, these telehealth visits. Focused didactic sessions, electronic handouts and/or quick access guides could empower more rural community providers to manage rheumatic diseases,” he concluded.<br/><br/>In the Q&A following the presentation, Laura Cappelli, MD, MHS, MS, associate professor of medicine in the division of rheumatology at Johns Hopkins School of Medicine in Baltimore, asked Dr. Rivadeneira how rheumatologists involved felt about the program and whether his team did any surveying or qualitative work with them.<br/><br/>“Just so you know, the rheumatologist was me,” he replied.<br/><br/>“I’m very picky about telemedicine,” he continued. “I don’t like it, I prefer, as most of us do, to have the patient there. But having the provider there, doing the exam, and you guiding them — I can ask, ‘Did you check their joints? Did you check their strength?’ — makes a huge difference and makes me feel comfortable with the sessions.”<br/><br/>Dr. Rivadeneira added that if a particular case was too complex or too vague to adequately assess via telehealth, he would arrange to see the patient in person.<br/><br/>The project was supported by the Arthritis Foundation. Dr. Rivadeneira and Dr. Cappelli reported no conflicts of interest.<br/><br/></p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/shared-telehealth-brings-rheumatology-care-rural-areas-2024a10007h3?src=">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM RA SUMMIT 2024
Could Modifying Gut Microbiota Enhance Response to Methotrexate in RA?
If your gut is telling you that your disease-modifying antirheumatic drugs (DMARDs) aren’t working as well as they should, listen to it.
That’s the advice of Rebecca B. Blank, MD, PhD, a rheumatologist at NYU Langone Health in New York City, who studies methods for modulating the gut microbiome to enhance DMARD efficacy for patients with rheumatoid arthritis (RA).
“The baseline gut microbiome can predict patient responsiveness to methotrexate,” said Dr. Blank at the 2024 Rheumatoid Arthritis Research Summit, presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City.
Dr. Blank and colleagues are investigating how the intestinal microbiome may influence drug metabolism and the therapeutic potential of short-chain fatty acids for improving the efficacy of methotrexate in patients with RA.
Mucosal Barrier Disruption
There are myriad factors contributing to the development and progression of RA, including dysbiosis, or disruption, of the mucosal barrier, Dr. Blank explained.
“Dysbiosis can be detected in at-risk individuals before clinical signs of rheumatoid arthritis even occur,” she said.
Dr. Blank cited a 2021 study of the gut-joint axis in RA,which indicated that subclinical inflammation in the oral, gut, and/or lung mucosa may lead to inflammatory arthritis.
“When there’s a break in the mucosal barrier, either bacteria or their bacterial products can translocate into the lamina propria and then lead to an inflammatory T-cell response, and in addition, bacteria or their products can induce auto-antibody formation, which can then lead to joint inflammation,” she said.
Dr. Blank and colleagues, as well as other research groups, showed that gut bacterial colonization by Prevotella copri can induce an inflammatory response in gut lamina propria, and that people with RA have increased abundance of P copri relative to people without RA.
DMARD Resistance
To see whether microbial dysbiosis might play a role in DMARD-resistant RA, Dr. Blank and her team looked at patients with new-onset RA who were scheduled for treatment with methotrexate as their first-line medication. They classified responders as those patients with a change in Disease Activity Score in 28 joints (DAS28) of at least 1.8 points.
They then conducted 16S rRNA sequencing and shotgun sequencing on patient fecal samples taken at baseline to determine whether baseline microbiome differences might contribute to responses to methotrexate.
“And so indeed, we were able to find a human gut microbial signature that predicted methotrexate responsiveness in these baseline microbiome samples,” Dr. Blank said.
They identified 462 differences in gene orthologs (ie, genes preserved during evolution and speciation) that differed between responders and nonresponders, narrowed the list down to the top 38, and then developed a predictive model for response to methotrexate with an area under the receiver operating characteristic curve of 0.84.
The investigators then cultured fecal baseline samples with methotrexate to see how levels of the drug would be affected over time and found that samples from nonresponders metabolized methotrexate at a faster rate than samples from patients who had clinical responses to the drug.
Their work was further supported by colleagues at the University of California San Francisco, who found evidence in mouse models to suggest that microbial metabolism plays a role in methotrexate levels in plasma.
Modulating the Gut
“Our next question was: Can we modulate the gut microbiome to improve methotrexate efficacy?” Dr. Blank said.
They considered probiotics and prebiotics as possible means for modulating gut microbiota, but evidence of efficacy for these agents has been decidedly mixed, she noted.
Instead, the investigators focused on short-chain fatty acids, gut microbial fermentation byproducts of indigestible carbohydrates, which have been demonstrated to help improve gut mucosal barrier integrity and promote a more tolerant immune response.
One such short-chain fatty acid, butyrate, is produced through microbial fermentation of dietary fiber in the colon; it is available in various foods and in supplement form.
Butyrate has been shown to ameliorate inflammatory arthritis in a collagen-induced arthritis model, and in this model, methotrexate efficacy was increased with the addition of butyrate or butyrate-producing bacterial species.
Dr. Blank and colleagues compared patients with new-onset RA treated with methotrexate alone or methotrexate plus butyrate for 4 months and looked at up to 2 months of methotrexate plus butyrate treatment in patients who had suboptimal response to methotrexate alone.
In preliminary analyses, they found that at baseline, fecal butyrate was significantly elevated in methotrexate responders compared with in nonresponders. In addition, in the new-onset RA cohort, they saw that the 4-month responsiveness rate was 52.6% for those treated with methotrexate compared with 64.7% for those treated with methotrexate plus butyrate.
“Although this difference was not statistically significant, it’s exciting to think we may have an impact. What’s more, we were really excited to find that oral butyrate can lead to increased microbial diversity,” she said.
What Are You Measuring?
In the Q & A following the presentation, Clifton O. Bingham III, MD, director of the Johns Hopkins Arthritis Center in Baltimore, Maryland, commented that “the definitions of response and nonresponse are quite variable, depending on the studies that you use, and I think this is potentially a real problem for this entire line of investigation.”
He noted that the DAS28, as used by Dr. Blank and colleagues, was developed in 1993, and that American College of Rheumatology response criteria, employed by other investigators who also presented during the session, were developed in 1990.
“It was a very different world when those criteria and those response indices were developed for patients with a very different disease from what we know as RA today,” he said.
He added that “I see a tremendous need for the rheumatology community to reevaluate what we define as responders and nonresponders, so that in all of these studies that are being done around the world, there is one definition that we understand [for] someone who is doing better, responding, or not responding.”
Dr. Blank’s work is supported by NYU, the Arthritis Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. She reported having no conflicts of interest to disclose. Dr. Bingham had no relevant conflicts of interest to disclose.
A version of this article appeared on Medscape.com.
If your gut is telling you that your disease-modifying antirheumatic drugs (DMARDs) aren’t working as well as they should, listen to it.
That’s the advice of Rebecca B. Blank, MD, PhD, a rheumatologist at NYU Langone Health in New York City, who studies methods for modulating the gut microbiome to enhance DMARD efficacy for patients with rheumatoid arthritis (RA).
“The baseline gut microbiome can predict patient responsiveness to methotrexate,” said Dr. Blank at the 2024 Rheumatoid Arthritis Research Summit, presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City.
Dr. Blank and colleagues are investigating how the intestinal microbiome may influence drug metabolism and the therapeutic potential of short-chain fatty acids for improving the efficacy of methotrexate in patients with RA.
Mucosal Barrier Disruption
There are myriad factors contributing to the development and progression of RA, including dysbiosis, or disruption, of the mucosal barrier, Dr. Blank explained.
“Dysbiosis can be detected in at-risk individuals before clinical signs of rheumatoid arthritis even occur,” she said.
Dr. Blank cited a 2021 study of the gut-joint axis in RA,which indicated that subclinical inflammation in the oral, gut, and/or lung mucosa may lead to inflammatory arthritis.
“When there’s a break in the mucosal barrier, either bacteria or their bacterial products can translocate into the lamina propria and then lead to an inflammatory T-cell response, and in addition, bacteria or their products can induce auto-antibody formation, which can then lead to joint inflammation,” she said.
Dr. Blank and colleagues, as well as other research groups, showed that gut bacterial colonization by Prevotella copri can induce an inflammatory response in gut lamina propria, and that people with RA have increased abundance of P copri relative to people without RA.
DMARD Resistance
To see whether microbial dysbiosis might play a role in DMARD-resistant RA, Dr. Blank and her team looked at patients with new-onset RA who were scheduled for treatment with methotrexate as their first-line medication. They classified responders as those patients with a change in Disease Activity Score in 28 joints (DAS28) of at least 1.8 points.
They then conducted 16S rRNA sequencing and shotgun sequencing on patient fecal samples taken at baseline to determine whether baseline microbiome differences might contribute to responses to methotrexate.
“And so indeed, we were able to find a human gut microbial signature that predicted methotrexate responsiveness in these baseline microbiome samples,” Dr. Blank said.
They identified 462 differences in gene orthologs (ie, genes preserved during evolution and speciation) that differed between responders and nonresponders, narrowed the list down to the top 38, and then developed a predictive model for response to methotrexate with an area under the receiver operating characteristic curve of 0.84.
The investigators then cultured fecal baseline samples with methotrexate to see how levels of the drug would be affected over time and found that samples from nonresponders metabolized methotrexate at a faster rate than samples from patients who had clinical responses to the drug.
Their work was further supported by colleagues at the University of California San Francisco, who found evidence in mouse models to suggest that microbial metabolism plays a role in methotrexate levels in plasma.
Modulating the Gut
“Our next question was: Can we modulate the gut microbiome to improve methotrexate efficacy?” Dr. Blank said.
They considered probiotics and prebiotics as possible means for modulating gut microbiota, but evidence of efficacy for these agents has been decidedly mixed, she noted.
Instead, the investigators focused on short-chain fatty acids, gut microbial fermentation byproducts of indigestible carbohydrates, which have been demonstrated to help improve gut mucosal barrier integrity and promote a more tolerant immune response.
One such short-chain fatty acid, butyrate, is produced through microbial fermentation of dietary fiber in the colon; it is available in various foods and in supplement form.
Butyrate has been shown to ameliorate inflammatory arthritis in a collagen-induced arthritis model, and in this model, methotrexate efficacy was increased with the addition of butyrate or butyrate-producing bacterial species.
Dr. Blank and colleagues compared patients with new-onset RA treated with methotrexate alone or methotrexate plus butyrate for 4 months and looked at up to 2 months of methotrexate plus butyrate treatment in patients who had suboptimal response to methotrexate alone.
In preliminary analyses, they found that at baseline, fecal butyrate was significantly elevated in methotrexate responders compared with in nonresponders. In addition, in the new-onset RA cohort, they saw that the 4-month responsiveness rate was 52.6% for those treated with methotrexate compared with 64.7% for those treated with methotrexate plus butyrate.
“Although this difference was not statistically significant, it’s exciting to think we may have an impact. What’s more, we were really excited to find that oral butyrate can lead to increased microbial diversity,” she said.
What Are You Measuring?
In the Q & A following the presentation, Clifton O. Bingham III, MD, director of the Johns Hopkins Arthritis Center in Baltimore, Maryland, commented that “the definitions of response and nonresponse are quite variable, depending on the studies that you use, and I think this is potentially a real problem for this entire line of investigation.”
He noted that the DAS28, as used by Dr. Blank and colleagues, was developed in 1993, and that American College of Rheumatology response criteria, employed by other investigators who also presented during the session, were developed in 1990.
“It was a very different world when those criteria and those response indices were developed for patients with a very different disease from what we know as RA today,” he said.
He added that “I see a tremendous need for the rheumatology community to reevaluate what we define as responders and nonresponders, so that in all of these studies that are being done around the world, there is one definition that we understand [for] someone who is doing better, responding, or not responding.”
Dr. Blank’s work is supported by NYU, the Arthritis Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. She reported having no conflicts of interest to disclose. Dr. Bingham had no relevant conflicts of interest to disclose.
A version of this article appeared on Medscape.com.
If your gut is telling you that your disease-modifying antirheumatic drugs (DMARDs) aren’t working as well as they should, listen to it.
That’s the advice of Rebecca B. Blank, MD, PhD, a rheumatologist at NYU Langone Health in New York City, who studies methods for modulating the gut microbiome to enhance DMARD efficacy for patients with rheumatoid arthritis (RA).
“The baseline gut microbiome can predict patient responsiveness to methotrexate,” said Dr. Blank at the 2024 Rheumatoid Arthritis Research Summit, presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City.
Dr. Blank and colleagues are investigating how the intestinal microbiome may influence drug metabolism and the therapeutic potential of short-chain fatty acids for improving the efficacy of methotrexate in patients with RA.
Mucosal Barrier Disruption
There are myriad factors contributing to the development and progression of RA, including dysbiosis, or disruption, of the mucosal barrier, Dr. Blank explained.
“Dysbiosis can be detected in at-risk individuals before clinical signs of rheumatoid arthritis even occur,” she said.
Dr. Blank cited a 2021 study of the gut-joint axis in RA,which indicated that subclinical inflammation in the oral, gut, and/or lung mucosa may lead to inflammatory arthritis.
“When there’s a break in the mucosal barrier, either bacteria or their bacterial products can translocate into the lamina propria and then lead to an inflammatory T-cell response, and in addition, bacteria or their products can induce auto-antibody formation, which can then lead to joint inflammation,” she said.
Dr. Blank and colleagues, as well as other research groups, showed that gut bacterial colonization by Prevotella copri can induce an inflammatory response in gut lamina propria, and that people with RA have increased abundance of P copri relative to people without RA.
DMARD Resistance
To see whether microbial dysbiosis might play a role in DMARD-resistant RA, Dr. Blank and her team looked at patients with new-onset RA who were scheduled for treatment with methotrexate as their first-line medication. They classified responders as those patients with a change in Disease Activity Score in 28 joints (DAS28) of at least 1.8 points.
They then conducted 16S rRNA sequencing and shotgun sequencing on patient fecal samples taken at baseline to determine whether baseline microbiome differences might contribute to responses to methotrexate.
“And so indeed, we were able to find a human gut microbial signature that predicted methotrexate responsiveness in these baseline microbiome samples,” Dr. Blank said.
They identified 462 differences in gene orthologs (ie, genes preserved during evolution and speciation) that differed between responders and nonresponders, narrowed the list down to the top 38, and then developed a predictive model for response to methotrexate with an area under the receiver operating characteristic curve of 0.84.
The investigators then cultured fecal baseline samples with methotrexate to see how levels of the drug would be affected over time and found that samples from nonresponders metabolized methotrexate at a faster rate than samples from patients who had clinical responses to the drug.
Their work was further supported by colleagues at the University of California San Francisco, who found evidence in mouse models to suggest that microbial metabolism plays a role in methotrexate levels in plasma.
Modulating the Gut
“Our next question was: Can we modulate the gut microbiome to improve methotrexate efficacy?” Dr. Blank said.
They considered probiotics and prebiotics as possible means for modulating gut microbiota, but evidence of efficacy for these agents has been decidedly mixed, she noted.
Instead, the investigators focused on short-chain fatty acids, gut microbial fermentation byproducts of indigestible carbohydrates, which have been demonstrated to help improve gut mucosal barrier integrity and promote a more tolerant immune response.
One such short-chain fatty acid, butyrate, is produced through microbial fermentation of dietary fiber in the colon; it is available in various foods and in supplement form.
Butyrate has been shown to ameliorate inflammatory arthritis in a collagen-induced arthritis model, and in this model, methotrexate efficacy was increased with the addition of butyrate or butyrate-producing bacterial species.
Dr. Blank and colleagues compared patients with new-onset RA treated with methotrexate alone or methotrexate plus butyrate for 4 months and looked at up to 2 months of methotrexate plus butyrate treatment in patients who had suboptimal response to methotrexate alone.
In preliminary analyses, they found that at baseline, fecal butyrate was significantly elevated in methotrexate responders compared with in nonresponders. In addition, in the new-onset RA cohort, they saw that the 4-month responsiveness rate was 52.6% for those treated with methotrexate compared with 64.7% for those treated with methotrexate plus butyrate.
“Although this difference was not statistically significant, it’s exciting to think we may have an impact. What’s more, we were really excited to find that oral butyrate can lead to increased microbial diversity,” she said.
What Are You Measuring?
In the Q & A following the presentation, Clifton O. Bingham III, MD, director of the Johns Hopkins Arthritis Center in Baltimore, Maryland, commented that “the definitions of response and nonresponse are quite variable, depending on the studies that you use, and I think this is potentially a real problem for this entire line of investigation.”
He noted that the DAS28, as used by Dr. Blank and colleagues, was developed in 1993, and that American College of Rheumatology response criteria, employed by other investigators who also presented during the session, were developed in 1990.
“It was a very different world when those criteria and those response indices were developed for patients with a very different disease from what we know as RA today,” he said.
He added that “I see a tremendous need for the rheumatology community to reevaluate what we define as responders and nonresponders, so that in all of these studies that are being done around the world, there is one definition that we understand [for] someone who is doing better, responding, or not responding.”
Dr. Blank’s work is supported by NYU, the Arthritis Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. She reported having no conflicts of interest to disclose. Dr. Bingham had no relevant conflicts of interest to disclose.
A version of this article appeared on Medscape.com.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>If your gut is telling you that your disease-modifying antirheumatic drugs (DMARDs) aren’t working as well as they should, listen to it.</metaDescription> <articlePDF/> <teaserImage>297286</teaserImage> <teaser>Investigators have found evidence suggesting that bad bugs in the belly may contribute to inflammation in the joints, and that modulating gut microbes could improve rheumatoid arthritis treatment.</teaser> <title>Could Modifying Gut Microbiota Enhance Response to Methotrexate in RA?</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>rn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">26</term> <term>21</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term canonical="true">289</term> <term>290</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24012174.jpg</altRep> <description role="drol:caption">Dr. Rebecca B. Blank</description> <description role="drol:credit"/> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24012844.jpg</altRep> <description role="drol:caption">Dr. Clifton O. Bingham III</description> <description role="drol:credit">Johns Hopkins Medicine, Johns Hopkins Division of Rheumatology</description> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Could Modifying Gut Microbiota Enhance Response to Methotrexate in RA?</title> <deck/> </itemMeta> <itemContent> <p>If your gut is telling you that your disease-modifying antirheumatic drugs (DMARDs) aren’t working as well as they should, listen to it.</p> <p>That’s the advice of Rebecca B. Blank, MD, PhD, a rheumatologist at NYU Langone Health in New York City, who studies methods for modulating the gut microbiome to enhance DMARD efficacy for patients with rheumatoid arthritis (RA).<br/><br/>“The baseline gut microbiome can predict patient responsiveness to <a href="https://reference.medscape.com/drug/trexall-otrexup-methotrexate-343201">methotrexate</a>,” said Dr. Blank at the <a href="https://www.medscape.com/viewcollection/37505">2024 Rheumatoid Arthritis Research Summit</a>, presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City.<br/><br/>[[{"fid":"297286","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Rebecca B. Blank, rheumatologist and instructor of medicine at NYU Langone Health in New York City","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"Dr. Rebecca B. Blank"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]Dr. Blank and colleagues are investigating how the intestinal microbiome may influence drug metabolism and the therapeutic potential of short-chain fatty acids for improving the efficacy of methotrexate in patients with RA.<br/><br/></p> <h2>Mucosal Barrier Disruption</h2> <p>There are myriad factors contributing to the development and progression of RA, including dysbiosis, or disruption, of the mucosal barrier, Dr. Blank explained.</p> <p>“Dysbiosis can be detected in at-risk individuals before clinical signs of rheumatoid arthritis even occur,” she said.<br/><br/>Dr. Blank cited a <a href="https://www.nature.com/articles/s41584-021-00585-3">2021 study</a> of the gut-joint axis in RA,which indicated that subclinical inflammation in the oral, gut, and/or lung mucosa may lead to inflammatory arthritis.<br/><br/>“When there’s a break in the mucosal barrier, either bacteria or their bacterial products can translocate into the lamina propria and then lead to an inflammatory T-cell response, and in addition, bacteria or their products can induce auto-antibody formation, which can then lead to joint inflammation,” she said.<br/><br/>Dr. Blank and colleagues, as well as other research groups, showed that gut bacterial colonization by <em>Prevotella copri</em> can induce an inflammatory response in gut lamina propria, and that people with RA have increased abundance of <em>P copri</em> relative to people without RA.<br/><br/></p> <h2>DMARD Resistance</h2> <p>To see whether microbial dysbiosis might play a role in DMARD-resistant RA, Dr. Blank and her team looked at patients with new-onset RA who were scheduled for treatment with methotrexate as their first-line medication. They classified responders as those patients with a change in Disease Activity Score in 28 joints (DAS28) of at least 1.8 points.</p> <p>They then conducted 16S rRNA sequencing and shotgun sequencing on patient fecal samples taken at baseline to determine whether baseline microbiome differences might contribute to responses to methotrexate.<br/><br/>“And so indeed, we were able to find a human gut microbial signature that predicted methotrexate responsiveness in these baseline microbiome samples,” Dr. Blank said.<br/><br/>They identified 462 differences in gene orthologs (ie, genes preserved during evolution and speciation) that differed between responders and nonresponders, narrowed the list down to the top 38, and then developed a predictive model for response to methotrexate with an area under the receiver operating characteristic curve of 0.84.<br/><br/>The investigators then cultured fecal baseline samples with methotrexate to see how levels of the drug would be affected over time and found that samples from nonresponders metabolized methotrexate at a faster rate than samples from patients who had clinical responses to the drug.<br/><br/>Their work was further supported by colleagues at the University of California San Francisco, who found evidence in mouse models to suggest that microbial metabolism plays a role in methotrexate levels in plasma.<br/><br/></p> <h2>Modulating the Gut</h2> <p>“Our next question was: Can we modulate the gut microbiome to improve methotrexate efficacy?” Dr. Blank said.</p> <p>They considered probiotics and prebiotics as possible means for modulating gut microbiota, but evidence of efficacy for these agents has been decidedly mixed, she noted.<br/><br/>Instead, the investigators focused on short-chain fatty acids, gut microbial fermentation byproducts of indigestible carbohydrates, which have been demonstrated to help improve gut mucosal barrier integrity and promote a more tolerant immune response.<br/><br/>One such short-chain fatty acid, butyrate, is produced through microbial fermentation of dietary fiber in the colon; it is available in various foods and in supplement form.<br/><br/>Butyrate has been shown to ameliorate inflammatory arthritis in a collagen-induced arthritis model, and in this model, methotrexate efficacy was increased with the addition of butyrate or butyrate-producing bacterial species.<br/><br/>Dr. Blank and colleagues compared patients with new-onset RA treated with methotrexate alone or methotrexate plus butyrate for 4 months and looked at up to 2 months of methotrexate plus butyrate treatment in patients who had suboptimal response to methotrexate alone.<br/><br/>In preliminary analyses, they found that at baseline, fecal butyrate was significantly elevated in methotrexate responders compared with in nonresponders. In addition, in the new-onset RA cohort, they saw that the 4-month responsiveness rate was 52.6% for those treated with methotrexate compared with 64.7% for those treated with methotrexate plus butyrate.<br/><br/>“Although this difference was not statistically significant, it’s exciting to think we may have an impact. What’s more, we were really excited to find that oral butyrate can lead to increased microbial diversity,” she said.<br/><br/></p> <h2>What Are You Measuring?</h2> <p>In the Q & A following the presentation, Clifton O. Bingham III, MD, director of the Johns Hopkins Arthritis Center in Baltimore, Maryland, commented that “the definitions of response and nonresponse are quite variable, depending on the studies that you use, and I think this is potentially a real problem for this entire line of investigation.”</p> <p>[[{"fid":"301134","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. Clifton O. Bingham III, director of the Johns Hopkins Arthritis Center in Baltimore, Maryland","field_file_image_credit[und][0][value]":"Johns Hopkins Medicine, Johns Hopkins Division of Rheumatology","field_file_image_caption[und][0][value]":"Dr. Clifton O. Bingham III"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]He noted that the DAS28, as used by Dr. Blank and colleagues, was developed in 1993, and that American College of Rheumatology response criteria, employed by other investigators who also presented during the session, were developed in 1990.<br/><br/>“It was a very different world when those criteria and those response indices were developed for patients with a very different disease from what we know as RA today,” he said.<br/><br/>He added that “I see a tremendous need for the rheumatology community to reevaluate what we define as responders and nonresponders, so that in all of these studies that are being done around the world, there is one definition that we understand [for] someone who is doing better, responding, or not responding.”<br/><br/>Dr. Blank’s work is supported by NYU, the Arthritis Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. She reported having no conflicts of interest to disclose. Dr. Bingham had no relevant conflicts of interest to disclose.<span class="end"/></p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/modifying-gut-microbiota-may-enhance-dmard-efficacy-ra-2024a10007dm">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM RA SUMMIT 2024
RA Flare Risk Rises Following DMARD Taper to Discontinuation With Conventional Synthetics or TNF Inhibitors
Patients with rheumatoid arthritis (RA) in remission who tapered and then fully stopped either conventional synthetic disease-modifying antirheumatic drug (csDMARD) or tumor necrosis factor (TNF)–inhibitor therapy experienced more disease flares than those who received stable dose treatment in an open-label, randomized trial.
In the 3-year trial, called ARCTIC REWIND, 80% of patients taking stable doses of only csMARDs remained flare-free compared with 38% in another treatment arm taking only csDMARDs who tapered to a half dose and then discontinued all after 1 year. In patients who continued to receive half-dose csDMARDs for the entire study period, 57% remained flare-free.
A separate two treatment arms of the study that assessed the effect of tapering TNF-inhibitor treatment to withdrawal showed that only 25% of patients who tapered TNF inhibitor to withdrawal remained flare-free over 3 years compared with 85% who remained on a stable TNF-inhibitor dose.
Though the risk for flare was higher in both the half-dose csDMARD and drug-free groups, the results also suggested that tapering medication “could be a realistic option for some patients with rheumatoid arthritis in sustained remission on csDMARDs,” wrote Kaja Kjørholt, MD, of the Center for Treatment of Rheumatic and Musculoskeletal Diseases at Diakonhjemmet Hospital in Oslo, Norway, and colleagues.
The 3-year results for the csDMARD-only arms of the trial were published in The Lancet Rheumatology. The 3-year results of the TNF-inhibitor arms of the study were presented as an abstract at the annual meeting of the American College of Rheumatology (ACR).
Don’t Avoid Tapering But Take an Individualized Approach
Many rheumatologists will taper patients with RA in remission to lower doses of medication, but the protocols for this study do not reflect clinical practice, noted James R. O’Dell, MD, chief of the Division of Rheumatology at the University of Nebraska Medical Center in Omaha, Nebraska. He was not involved with the research.
“I don’t know of any rheumatologist who would ever think that it was a good idea to taper somebody completely off of all DMARDs,” he told this news organization. “The only surprise is that more of them didn’t flare,” he continued, though he suspected that more patients would flare if they were followed for more time. Rheumatologists also would take a much more individualized approach when tapering to lower doses, he added, and do so at a much slower rate than what was observed in this study.
Both the ACR and the European Alliance of Associations for Rheumatology recommendations for the management of RA stated that tapering DMARDs can be considered for patients who have sustained remission, but they do not mention discontinuing medication entirely.
In the TNF-inhibitor arms of the trial, the tapering group received a half dose of a TNF inhibitor for 4 months before stopping therapy entirely, which Dr. O’Dell noted was a large dip in too short a period.
“Nobody should be surprised that these people flared a lot,” he said. However, tapering to lower doses of a TNF inhibitor can be successful, he noted, adding that more than half of his patients taking a TNF inhibitor are on less than their original dose. Completely tapering off a TNF inhibitor is less common and depends on what other DMARDs a patient is taking, he said, and complete drug-free remission in this population is highly unlikely.
Dr. O’Dell emphasized that the takeaway from these results should not be to avoid tapering medication because of flare risk but instead a tailored approach — something that is not possible with a study protocol — is needed.
“We want our patients to have all the medicine they need and no more,” he said. “That sweet spot is different for each individual patient for how much TNF inhibition or how much conventional therapy they need. If we’re thoughtful about that in the clinic, we can find that sweet spot,” he said.
Details of ARCTIC REWIND
The open-label ARCTIC REWIND trial enrolled patients with RA in sustained remission, determined via Disease Activity Score (DAS), from 10 different hospitals in Norway. Researchers enrolled 160 patients in the csDMARD-only arms and randomized them to receive stable dose csDMARDs for 3 years or half-dose csDMARDs for 1 year, followed by complete withdrawal for the next 2 years; withdrawal of csDMARDs was only done in patients who had not had a flare during the first year. Participants had scheduled clinic visits every 4 months, and full-dose csDMARD therapy was resumed in patients who experienced disease flares.
There was a total of 99 patients randomized in the TNF-inhibitor arms to continue stable TNF-inhibitor therapy or to taper to a half dose for 4 months before discontinuing therapy. Like the csDMARD study, clinic visits occurred every 4 months, and full-dose therapy was resumed if a flare occurred. Patients taking a TNF inhibitor could also take a csDMARD as needed.
Last year, 1-year results for the csDMARD arms were published in JAMA, and 1-year results for the TNF-inhibitor arms were reported in Annals of the Rheumatic Diseases.
At baseline, most patients across the three csDMARD groups (81%) had received methotrexate monotherapy. Triple therapy (methotrexate, sulfasalazine, and hydroxychloroquine) was used in 13% of the stable-dose group, 7% of the half-dose group, and 8% of the half-dose tapering to withdrawal group. Seven individuals in the stable-dose group, three individuals in the half-dose group, and three individuals the half-dose tapering to withdrawal group used other mono/duo therapies.
A total of 139 participants in the csDMARD-only arms completed 3 years of follow-up, with 68 in the stable-dose group, 36 in the half-dose group, and 35 in the half-dose tapering to withdrawal group.
Compared with the stable-dose group, the risk for flare was more than four times higher in the half-dose tapering to withdrawal group (hazard ratio [HR], 4.2; 95% CI, 2.2-8.2) and about three times higher in the half-dose group (HR, 2.9; 95% CI, 1.5-5.9). The flare risk between the half dose and half-dose tapering to withdrawal group was not statistically significant.
Most patients regained DAS remission status in the next clinic visit following a flare, the authors reported. Comparing the last visit to baseline, 10 patients in the taper-to-withdrawal group (27%) had increased treatment — either by adding a biologic or increasing csDMARD dose — compared with one patient (3%) in the half-dose group and 11 patients (14%) in the stable-dose group. Adverse events were common across all three groups, though were highest in the tapering to withdrawal group.
In the TNF-inhibitor arms, a total of 80 patients completed the 3-year follow-up. By the end of 3 years, 75% of the tapering group experienced a disease flare compared with 15% of the stable TNF-inhibitor group. Most patients regained DAS remission status in the next clinic visit following a flare, the authors reported. During the study, 23% of the tapering group and 13% of the stable TNF-inhibitor group used systemic glucocorticoids. Four patients in the tapering group and two patients in the stable TNF-inhibitor group switched to another TNF inhibitor during the study. An additional two patients in the stable TNF-inhibitor group switched to a Janus kinase inhibitor during the 3-year study.
Adverse events were similar in both treatment groups, but serious adverse events were more common in the tapering group (21%) than in the stable-dose group (11%).
The authors concluded that the findings did not support tapering a TNF inhibitor to withdrawal for patients in sustained remission, but they noted that additional research is needed to identify which patients would fare better or worse tapering csDMARDs.
ARCTIC REWIND was funded by grants from The Research Council of Norway and The South-Eastern Norway Regional Health Authorities. Many of the authors disclosed financial ties to pharmaceutical companies. Dr. O’Dell disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Patients with rheumatoid arthritis (RA) in remission who tapered and then fully stopped either conventional synthetic disease-modifying antirheumatic drug (csDMARD) or tumor necrosis factor (TNF)–inhibitor therapy experienced more disease flares than those who received stable dose treatment in an open-label, randomized trial.
In the 3-year trial, called ARCTIC REWIND, 80% of patients taking stable doses of only csMARDs remained flare-free compared with 38% in another treatment arm taking only csDMARDs who tapered to a half dose and then discontinued all after 1 year. In patients who continued to receive half-dose csDMARDs for the entire study period, 57% remained flare-free.
A separate two treatment arms of the study that assessed the effect of tapering TNF-inhibitor treatment to withdrawal showed that only 25% of patients who tapered TNF inhibitor to withdrawal remained flare-free over 3 years compared with 85% who remained on a stable TNF-inhibitor dose.
Though the risk for flare was higher in both the half-dose csDMARD and drug-free groups, the results also suggested that tapering medication “could be a realistic option for some patients with rheumatoid arthritis in sustained remission on csDMARDs,” wrote Kaja Kjørholt, MD, of the Center for Treatment of Rheumatic and Musculoskeletal Diseases at Diakonhjemmet Hospital in Oslo, Norway, and colleagues.
The 3-year results for the csDMARD-only arms of the trial were published in The Lancet Rheumatology. The 3-year results of the TNF-inhibitor arms of the study were presented as an abstract at the annual meeting of the American College of Rheumatology (ACR).
Don’t Avoid Tapering But Take an Individualized Approach
Many rheumatologists will taper patients with RA in remission to lower doses of medication, but the protocols for this study do not reflect clinical practice, noted James R. O’Dell, MD, chief of the Division of Rheumatology at the University of Nebraska Medical Center in Omaha, Nebraska. He was not involved with the research.
“I don’t know of any rheumatologist who would ever think that it was a good idea to taper somebody completely off of all DMARDs,” he told this news organization. “The only surprise is that more of them didn’t flare,” he continued, though he suspected that more patients would flare if they were followed for more time. Rheumatologists also would take a much more individualized approach when tapering to lower doses, he added, and do so at a much slower rate than what was observed in this study.
Both the ACR and the European Alliance of Associations for Rheumatology recommendations for the management of RA stated that tapering DMARDs can be considered for patients who have sustained remission, but they do not mention discontinuing medication entirely.
In the TNF-inhibitor arms of the trial, the tapering group received a half dose of a TNF inhibitor for 4 months before stopping therapy entirely, which Dr. O’Dell noted was a large dip in too short a period.
“Nobody should be surprised that these people flared a lot,” he said. However, tapering to lower doses of a TNF inhibitor can be successful, he noted, adding that more than half of his patients taking a TNF inhibitor are on less than their original dose. Completely tapering off a TNF inhibitor is less common and depends on what other DMARDs a patient is taking, he said, and complete drug-free remission in this population is highly unlikely.
Dr. O’Dell emphasized that the takeaway from these results should not be to avoid tapering medication because of flare risk but instead a tailored approach — something that is not possible with a study protocol — is needed.
“We want our patients to have all the medicine they need and no more,” he said. “That sweet spot is different for each individual patient for how much TNF inhibition or how much conventional therapy they need. If we’re thoughtful about that in the clinic, we can find that sweet spot,” he said.
Details of ARCTIC REWIND
The open-label ARCTIC REWIND trial enrolled patients with RA in sustained remission, determined via Disease Activity Score (DAS), from 10 different hospitals in Norway. Researchers enrolled 160 patients in the csDMARD-only arms and randomized them to receive stable dose csDMARDs for 3 years or half-dose csDMARDs for 1 year, followed by complete withdrawal for the next 2 years; withdrawal of csDMARDs was only done in patients who had not had a flare during the first year. Participants had scheduled clinic visits every 4 months, and full-dose csDMARD therapy was resumed in patients who experienced disease flares.
There was a total of 99 patients randomized in the TNF-inhibitor arms to continue stable TNF-inhibitor therapy or to taper to a half dose for 4 months before discontinuing therapy. Like the csDMARD study, clinic visits occurred every 4 months, and full-dose therapy was resumed if a flare occurred. Patients taking a TNF inhibitor could also take a csDMARD as needed.
Last year, 1-year results for the csDMARD arms were published in JAMA, and 1-year results for the TNF-inhibitor arms were reported in Annals of the Rheumatic Diseases.
At baseline, most patients across the three csDMARD groups (81%) had received methotrexate monotherapy. Triple therapy (methotrexate, sulfasalazine, and hydroxychloroquine) was used in 13% of the stable-dose group, 7% of the half-dose group, and 8% of the half-dose tapering to withdrawal group. Seven individuals in the stable-dose group, three individuals in the half-dose group, and three individuals the half-dose tapering to withdrawal group used other mono/duo therapies.
A total of 139 participants in the csDMARD-only arms completed 3 years of follow-up, with 68 in the stable-dose group, 36 in the half-dose group, and 35 in the half-dose tapering to withdrawal group.
Compared with the stable-dose group, the risk for flare was more than four times higher in the half-dose tapering to withdrawal group (hazard ratio [HR], 4.2; 95% CI, 2.2-8.2) and about three times higher in the half-dose group (HR, 2.9; 95% CI, 1.5-5.9). The flare risk between the half dose and half-dose tapering to withdrawal group was not statistically significant.
Most patients regained DAS remission status in the next clinic visit following a flare, the authors reported. Comparing the last visit to baseline, 10 patients in the taper-to-withdrawal group (27%) had increased treatment — either by adding a biologic or increasing csDMARD dose — compared with one patient (3%) in the half-dose group and 11 patients (14%) in the stable-dose group. Adverse events were common across all three groups, though were highest in the tapering to withdrawal group.
In the TNF-inhibitor arms, a total of 80 patients completed the 3-year follow-up. By the end of 3 years, 75% of the tapering group experienced a disease flare compared with 15% of the stable TNF-inhibitor group. Most patients regained DAS remission status in the next clinic visit following a flare, the authors reported. During the study, 23% of the tapering group and 13% of the stable TNF-inhibitor group used systemic glucocorticoids. Four patients in the tapering group and two patients in the stable TNF-inhibitor group switched to another TNF inhibitor during the study. An additional two patients in the stable TNF-inhibitor group switched to a Janus kinase inhibitor during the 3-year study.
Adverse events were similar in both treatment groups, but serious adverse events were more common in the tapering group (21%) than in the stable-dose group (11%).
The authors concluded that the findings did not support tapering a TNF inhibitor to withdrawal for patients in sustained remission, but they noted that additional research is needed to identify which patients would fare better or worse tapering csDMARDs.
ARCTIC REWIND was funded by grants from The Research Council of Norway and The South-Eastern Norway Regional Health Authorities. Many of the authors disclosed financial ties to pharmaceutical companies. Dr. O’Dell disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Patients with rheumatoid arthritis (RA) in remission who tapered and then fully stopped either conventional synthetic disease-modifying antirheumatic drug (csDMARD) or tumor necrosis factor (TNF)–inhibitor therapy experienced more disease flares than those who received stable dose treatment in an open-label, randomized trial.
In the 3-year trial, called ARCTIC REWIND, 80% of patients taking stable doses of only csMARDs remained flare-free compared with 38% in another treatment arm taking only csDMARDs who tapered to a half dose and then discontinued all after 1 year. In patients who continued to receive half-dose csDMARDs for the entire study period, 57% remained flare-free.
A separate two treatment arms of the study that assessed the effect of tapering TNF-inhibitor treatment to withdrawal showed that only 25% of patients who tapered TNF inhibitor to withdrawal remained flare-free over 3 years compared with 85% who remained on a stable TNF-inhibitor dose.
Though the risk for flare was higher in both the half-dose csDMARD and drug-free groups, the results also suggested that tapering medication “could be a realistic option for some patients with rheumatoid arthritis in sustained remission on csDMARDs,” wrote Kaja Kjørholt, MD, of the Center for Treatment of Rheumatic and Musculoskeletal Diseases at Diakonhjemmet Hospital in Oslo, Norway, and colleagues.
The 3-year results for the csDMARD-only arms of the trial were published in The Lancet Rheumatology. The 3-year results of the TNF-inhibitor arms of the study were presented as an abstract at the annual meeting of the American College of Rheumatology (ACR).
Don’t Avoid Tapering But Take an Individualized Approach
Many rheumatologists will taper patients with RA in remission to lower doses of medication, but the protocols for this study do not reflect clinical practice, noted James R. O’Dell, MD, chief of the Division of Rheumatology at the University of Nebraska Medical Center in Omaha, Nebraska. He was not involved with the research.
“I don’t know of any rheumatologist who would ever think that it was a good idea to taper somebody completely off of all DMARDs,” he told this news organization. “The only surprise is that more of them didn’t flare,” he continued, though he suspected that more patients would flare if they were followed for more time. Rheumatologists also would take a much more individualized approach when tapering to lower doses, he added, and do so at a much slower rate than what was observed in this study.
Both the ACR and the European Alliance of Associations for Rheumatology recommendations for the management of RA stated that tapering DMARDs can be considered for patients who have sustained remission, but they do not mention discontinuing medication entirely.
In the TNF-inhibitor arms of the trial, the tapering group received a half dose of a TNF inhibitor for 4 months before stopping therapy entirely, which Dr. O’Dell noted was a large dip in too short a period.
“Nobody should be surprised that these people flared a lot,” he said. However, tapering to lower doses of a TNF inhibitor can be successful, he noted, adding that more than half of his patients taking a TNF inhibitor are on less than their original dose. Completely tapering off a TNF inhibitor is less common and depends on what other DMARDs a patient is taking, he said, and complete drug-free remission in this population is highly unlikely.
Dr. O’Dell emphasized that the takeaway from these results should not be to avoid tapering medication because of flare risk but instead a tailored approach — something that is not possible with a study protocol — is needed.
“We want our patients to have all the medicine they need and no more,” he said. “That sweet spot is different for each individual patient for how much TNF inhibition or how much conventional therapy they need. If we’re thoughtful about that in the clinic, we can find that sweet spot,” he said.
Details of ARCTIC REWIND
The open-label ARCTIC REWIND trial enrolled patients with RA in sustained remission, determined via Disease Activity Score (DAS), from 10 different hospitals in Norway. Researchers enrolled 160 patients in the csDMARD-only arms and randomized them to receive stable dose csDMARDs for 3 years or half-dose csDMARDs for 1 year, followed by complete withdrawal for the next 2 years; withdrawal of csDMARDs was only done in patients who had not had a flare during the first year. Participants had scheduled clinic visits every 4 months, and full-dose csDMARD therapy was resumed in patients who experienced disease flares.
There was a total of 99 patients randomized in the TNF-inhibitor arms to continue stable TNF-inhibitor therapy or to taper to a half dose for 4 months before discontinuing therapy. Like the csDMARD study, clinic visits occurred every 4 months, and full-dose therapy was resumed if a flare occurred. Patients taking a TNF inhibitor could also take a csDMARD as needed.
Last year, 1-year results for the csDMARD arms were published in JAMA, and 1-year results for the TNF-inhibitor arms were reported in Annals of the Rheumatic Diseases.
At baseline, most patients across the three csDMARD groups (81%) had received methotrexate monotherapy. Triple therapy (methotrexate, sulfasalazine, and hydroxychloroquine) was used in 13% of the stable-dose group, 7% of the half-dose group, and 8% of the half-dose tapering to withdrawal group. Seven individuals in the stable-dose group, three individuals in the half-dose group, and three individuals the half-dose tapering to withdrawal group used other mono/duo therapies.
A total of 139 participants in the csDMARD-only arms completed 3 years of follow-up, with 68 in the stable-dose group, 36 in the half-dose group, and 35 in the half-dose tapering to withdrawal group.
Compared with the stable-dose group, the risk for flare was more than four times higher in the half-dose tapering to withdrawal group (hazard ratio [HR], 4.2; 95% CI, 2.2-8.2) and about three times higher in the half-dose group (HR, 2.9; 95% CI, 1.5-5.9). The flare risk between the half dose and half-dose tapering to withdrawal group was not statistically significant.
Most patients regained DAS remission status in the next clinic visit following a flare, the authors reported. Comparing the last visit to baseline, 10 patients in the taper-to-withdrawal group (27%) had increased treatment — either by adding a biologic or increasing csDMARD dose — compared with one patient (3%) in the half-dose group and 11 patients (14%) in the stable-dose group. Adverse events were common across all three groups, though were highest in the tapering to withdrawal group.
In the TNF-inhibitor arms, a total of 80 patients completed the 3-year follow-up. By the end of 3 years, 75% of the tapering group experienced a disease flare compared with 15% of the stable TNF-inhibitor group. Most patients regained DAS remission status in the next clinic visit following a flare, the authors reported. During the study, 23% of the tapering group and 13% of the stable TNF-inhibitor group used systemic glucocorticoids. Four patients in the tapering group and two patients in the stable TNF-inhibitor group switched to another TNF inhibitor during the study. An additional two patients in the stable TNF-inhibitor group switched to a Janus kinase inhibitor during the 3-year study.
Adverse events were similar in both treatment groups, but serious adverse events were more common in the tapering group (21%) than in the stable-dose group (11%).
The authors concluded that the findings did not support tapering a TNF inhibitor to withdrawal for patients in sustained remission, but they noted that additional research is needed to identify which patients would fare better or worse tapering csDMARDs.
ARCTIC REWIND was funded by grants from The Research Council of Norway and The South-Eastern Norway Regional Health Authorities. Many of the authors disclosed financial ties to pharmaceutical companies. Dr. O’Dell disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>Patients with rheumatoid arthritis (RA) in remission who tapered and then fully stopped either conventional synthetic disease-modifying antirheumatic drug (csDM</metaDescription> <articlePDF/> <teaserImage>301131</teaserImage> <teaser>In the ARCTIC REWIND trial, most patients with RA in remission who tapered csDMARD or TNF-inhibitor drugs to withdrawal experienced flares within 3 years.</teaser> <title>RA Flare Risk Rises Following DMARD Taper to Discontinuation With Conventional Synthetics or TNF Inhibitors</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>rn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">26</term> <term>21</term> <term>15</term> </publications> <sections> <term canonical="true">27970</term> <term>39313</term> </sections> <topics> <term canonical="true">289</term> <term>290</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/2401283c.jpg</altRep> <description role="drol:caption">Dr. James O'Dell</description> <description role="drol:credit">University of Nebraska Medical Center</description> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>RA Flare Risk Rises Following DMARD Taper to Discontinuation With Conventional Synthetics or TNF Inhibitors</title> <deck/> </itemMeta> <itemContent> <p>Patients with <span class="Hyperlink"><a href="https://emedicine.medscape.com/article/331715-overview">rheumatoid arthritis</a></span> (RA) in remission who tapered and then fully stopped either conventional synthetic disease-modifying antirheumatic drug (csDMARD) or tumor necrosis factor (TNF)–inhibitor therapy experienced more disease flares than those who received stable dose treatment in an open-label, randomized trial.</p> <p>In the 3-year trial, called <span class="Hyperlink"><a href="https://clinicaltrials.gov/study/NCT01881308">ARCTIC REWIND</a></span>, 80% of patients taking stable doses of only csMARDs remained flare-free compared with 38% in another treatment arm taking only csDMARDs who tapered to a half dose and then discontinued all after 1 year. In patients who continued to receive half-dose csDMARDs for the entire study period, 57% remained flare-free.<br/><br/>[[{"fid":"301131","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. James O'Dell","field_file_image_credit[und][0][value]":"University of Nebraska Medical Center","field_file_image_caption[und][0][value]":"Dr. James O'Dell"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]A separate two treatment arms of the study that assessed the effect of tapering TNF-inhibitor treatment to withdrawal showed that only 25% of patients who tapered TNF inhibitor to withdrawal remained flare-free over 3 years compared with 85% who remained on a stable TNF-inhibitor dose.<br/><br/>Though the risk for flare was higher in both the half-dose csDMARD and drug-free groups, the results also suggested that tapering medication “could be a realistic option for some patients with rheumatoid arthritis in sustained remission on csDMARDs,” wrote Kaja Kjørholt, MD, of the Center for Treatment of Rheumatic and Musculoskeletal Diseases at Diakonhjemmet Hospital in Oslo, Norway, and colleagues.<br/><br/>The 3-year results for the csDMARD-only arms of the trial <span class="Hyperlink"><a href="https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(24)00021-3/abstract">were published</a></span> in <em>The Lancet Rheumatology</em>. The 3-year results of the TNF-inhibitor arms of the study were <span class="Hyperlink"><a href="https://acrabstracts.org/abstract/3-year-results-of-tapering-tnfi-to-withdrawal-compared-to-stable-tnfi-among-rheumatoid-arthritis-patients-in-sustained-remission-a-multicenter-randomized-trial/">presented as an abstract</a></span> at the annual meeting of the American College of Rheumatology (ACR).<br/><br/></p> <h2>Don’t Avoid Tapering But Take an Individualized Approach</h2> <p>Many rheumatologists will taper patients with RA in remission to lower doses of medication, but the protocols for this study do not reflect clinical practice, noted James R. O’Dell, MD, chief of the Division of Rheumatology at the University of Nebraska Medical Center in Omaha, Nebraska. He was not involved with the research.</p> <p>“I don’t know of any rheumatologist who would ever think that it was a good idea to taper somebody completely off of all DMARDs,” he told this news organization. “The only surprise is that more of them didn’t flare,” he continued, though he suspected that more patients would flare if they were followed for more time. Rheumatologists also would take a much more individualized approach when tapering to lower doses, he added, and do so at a much slower rate than what was observed in this study.<br/><br/>Both the ACR and the European Alliance of Associations for Rheumatology recommendations for the management of RA stated that tapering DMARDs can be considered for patients who have sustained remission, but they do not mention discontinuing medication entirely.<br/><br/>In the TNF-inhibitor arms of the trial, the tapering group received a half dose of a TNF inhibitor for 4 months before stopping therapy entirely, which Dr. O’Dell noted was a large dip in too short a period.<br/><br/>“Nobody should be surprised that these people flared a lot,” he said. However, tapering to lower doses of a TNF inhibitor can be successful, he noted, adding that more than half of his patients taking a TNF inhibitor are on less than their original dose. Completely tapering off a TNF inhibitor is less common and depends on what other DMARDs a patient is taking, he said, and complete drug-free remission in this population is highly unlikely.<br/><br/>Dr. O’Dell emphasized that the takeaway from these results should not be to avoid tapering medication because of flare risk but instead a tailored approach — something that is not possible with a study protocol — is needed.<br/><br/>“We want our patients to have all the medicine they need and no more,” he said. “That sweet spot is different for each individual patient for how much TNF inhibition or how much conventional therapy they need. If we’re thoughtful about that in the clinic, we can find that sweet spot,” he said.<br/><br/></p> <h2>Details of ARCTIC REWIND</h2> <p>The open-label ARCTIC REWIND trial enrolled patients with RA in sustained remission, determined via Disease Activity Score (DAS), from 10 different hospitals in Norway. Researchers enrolled 160 patients in the csDMARD-only arms and randomized them to receive stable dose csDMARDs for 3 years or half-dose csDMARDs for 1 year, followed by complete withdrawal for the next 2 years; withdrawal of csDMARDs was only done in patients who had not had a flare during the first year. Participants had scheduled clinic visits every 4 months, and full-dose csDMARD therapy was resumed in patients who experienced disease flares.</p> <p>There was a total of 99 patients randomized in the TNF-inhibitor arms to continue stable TNF-inhibitor therapy or to taper to a half dose for 4 months before discontinuing therapy. Like the csDMARD study, clinic visits occurred every 4 months, and full-dose therapy was resumed if a flare occurred. Patients taking a TNF inhibitor could also take a csDMARD as needed.<br/><br/>Last year, 1-year results for the csDMARD arms were <a href="https://www.medscape.com/viewarticle/990175"><span class="Hyperlink">published in </span><em>JAMA</em></a>, and 1-year results for the TNF-inhibitor arms <span class="Hyperlink"><a href="https://ard.bmj.com/content/82/11/1394.long">were reported</a></span> in <em>Annals of the Rheumatic Diseases.</em><br/><br/>At baseline, most patients across the three csDMARD groups (81%) had received <span class="Hyperlink"><a href="https://reference.medscape.com/drug/trexall-otrexup-methotrexate-343201">methotrexate</a></span> monotherapy. Triple therapy (methotrexate, <span class="Hyperlink"><a href="https://reference.medscape.com/drug/azulfidine-sulfasalazine-343280">sulfasalazine</a></span>, and hydroxychloroquine) was used in 13% of the stable-dose group, 7% of the half-dose group, and 8% of the half-dose tapering to withdrawal group. Seven individuals in the stable-dose group, three individuals in the half-dose group, and three individuals the half-dose tapering to withdrawal group used other mono/duo therapies.<br/><br/>A total of 139 participants in the csDMARD-only arms completed 3 years of follow-up, with 68 in the stable-dose group, 36 in the half-dose group, and 35 in the half-dose tapering to withdrawal group.<br/><br/>Compared with the stable-dose group, the risk for flare was more than four times higher in the half-dose tapering to withdrawal group (hazard ratio [HR], 4.2; 95% CI, 2.2-8.2) and about three times higher in the half-dose group (HR, 2.9; 95% CI, 1.5-5.9). The flare risk between the half dose and half-dose tapering to withdrawal group was not statistically significant.<br/><br/>Most patients regained DAS remission status in the next clinic visit following a flare, the authors reported. Comparing the last visit to baseline, 10 patients in the taper-to-withdrawal group (27%) had increased treatment — either by adding a biologic or increasing csDMARD dose — compared with one patient (3%) in the half-dose group and 11 patients (14%) in the stable-dose group. Adverse events were common across all three groups, though were highest in the tapering to withdrawal group.<br/><br/>In the TNF-inhibitor arms, a total of 80 patients completed the 3-year follow-up. By the end of 3 years, 75% of the tapering group experienced a disease flare compared with 15% of the stable TNF-inhibitor group. Most patients regained DAS remission status in the next clinic visit following a flare, the authors reported. During the study, 23% of the tapering group and 13% of the stable TNF-inhibitor group used systemic glucocorticoids. Four patients in the tapering group and two patients in the stable TNF-inhibitor group switched to another TNF inhibitor during the study. An additional two patients in the stable TNF-inhibitor group switched to a Janus kinase inhibitor during the 3-year study.<br/><br/>Adverse events were similar in both treatment groups, but serious adverse events were more common in the tapering group (21%) than in the stable-dose group (11%).<br/><br/>The authors concluded that the findings did not support tapering a TNF inhibitor to withdrawal for patients in sustained remission, but they noted that additional research is needed to identify which patients would fare better or worse tapering csDMARDs.<br/><br/>ARCTIC REWIND was funded by grants from The Research Council of Norway and The South-Eastern Norway Regional Health Authorities. Many of the authors disclosed financial ties to pharmaceutical companies. Dr. O’Dell disclosed no relevant financial relationships.<span class="end"/></p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/dmard-taper-discontinuation-conventional-synthetics-or-tnf-2024a100073o?src=">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
High Infection Risk in Rheumatoid Arthritis–Associated Interstitial Lung Disease
TOPLINE:
METHODOLOGY:
- Patients with RA who have extra-articular manifestations such as ILD are highly susceptible to infections, but information on the types of infections, risk factors, and associations of infections with hospitalization and mortality is limited.
- This prospective multicenter cohort study evaluated infections in a cohort of 148 patients with RA-ILD (average age, 70 years; 57% women) recruited from 11 university hospitals in Spain between March 2015 and March 2023.
- Joint, lung, and any infection-related variables were evaluated using clinical and laboratory evaluations at baseline and selected time points till the end of the follow-up period (mean, 56.7 months).
- Researchers also investigated the common infectious sites, the etiology of the infection, vaccination status, variables associated with lung function, and clinical-therapeutic variables associated with RA.
TAKEAWAY:
- During the follow-up period, almost all (96%) patients had at least one infection, with the median time to first infection being 21.2 months and 65% of the deaths being directly related to infections.
- Respiratory infections were the most common first infections (74%) and led to death in 80% of the patients. Urinary tract (9.9%) and skin and soft tissue (9.1%) infections were the second and third most common first infections, respectively.
- Most infections were caused by SARS-CoV-2 (33.5%), Streptococcus pneumoniae (11.9%), Escherichia coli (11.9%), and Pseudomonas aeruginosa (11.1%), with mortality at 25.8% for SARS-CoV-2, 12.9% for P aeruginosa (12.9%), and 9.6% for pneumococci (9.6%).
- Increased age, disease activity, and the use of corticosteroids were associated with an elevated risk for infection and mortality in patients with RA-ILD.
IN PRACTICE:
“Our results demonstrate a high occurrence of serious infections among these patients, occurring early, recurring frequently, and proving fatal in 65% of cases,” the authors wrote.
SOURCE:
This study was led by Natalia Mena-Vázquez, MD, PhD, from Instituto de Investigación Biomédica de Málaga-Plataforma Bionand, Málaga, Spain, and published online March 27 in Frontiers in Immunology.
LIMITATIONS:
The findings of this study have been affected by the COVID-19 pandemic. The lack of a control group also limited the ability of this study to establish any causal relationships between ILD and the clinical outcomes analyzed.
DISCLOSURE:
This study was supported by Redes de Investigación Cooperativa Orientadas a Resultados en Salud and Fundación Andaluza de Reumatología. The authors declared having no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Patients with RA who have extra-articular manifestations such as ILD are highly susceptible to infections, but information on the types of infections, risk factors, and associations of infections with hospitalization and mortality is limited.
- This prospective multicenter cohort study evaluated infections in a cohort of 148 patients with RA-ILD (average age, 70 years; 57% women) recruited from 11 university hospitals in Spain between March 2015 and March 2023.
- Joint, lung, and any infection-related variables were evaluated using clinical and laboratory evaluations at baseline and selected time points till the end of the follow-up period (mean, 56.7 months).
- Researchers also investigated the common infectious sites, the etiology of the infection, vaccination status, variables associated with lung function, and clinical-therapeutic variables associated with RA.
TAKEAWAY:
- During the follow-up period, almost all (96%) patients had at least one infection, with the median time to first infection being 21.2 months and 65% of the deaths being directly related to infections.
- Respiratory infections were the most common first infections (74%) and led to death in 80% of the patients. Urinary tract (9.9%) and skin and soft tissue (9.1%) infections were the second and third most common first infections, respectively.
- Most infections were caused by SARS-CoV-2 (33.5%), Streptococcus pneumoniae (11.9%), Escherichia coli (11.9%), and Pseudomonas aeruginosa (11.1%), with mortality at 25.8% for SARS-CoV-2, 12.9% for P aeruginosa (12.9%), and 9.6% for pneumococci (9.6%).
- Increased age, disease activity, and the use of corticosteroids were associated with an elevated risk for infection and mortality in patients with RA-ILD.
IN PRACTICE:
“Our results demonstrate a high occurrence of serious infections among these patients, occurring early, recurring frequently, and proving fatal in 65% of cases,” the authors wrote.
SOURCE:
This study was led by Natalia Mena-Vázquez, MD, PhD, from Instituto de Investigación Biomédica de Málaga-Plataforma Bionand, Málaga, Spain, and published online March 27 in Frontiers in Immunology.
LIMITATIONS:
The findings of this study have been affected by the COVID-19 pandemic. The lack of a control group also limited the ability of this study to establish any causal relationships between ILD and the clinical outcomes analyzed.
DISCLOSURE:
This study was supported by Redes de Investigación Cooperativa Orientadas a Resultados en Salud and Fundación Andaluza de Reumatología. The authors declared having no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Patients with RA who have extra-articular manifestations such as ILD are highly susceptible to infections, but information on the types of infections, risk factors, and associations of infections with hospitalization and mortality is limited.
- This prospective multicenter cohort study evaluated infections in a cohort of 148 patients with RA-ILD (average age, 70 years; 57% women) recruited from 11 university hospitals in Spain between March 2015 and March 2023.
- Joint, lung, and any infection-related variables were evaluated using clinical and laboratory evaluations at baseline and selected time points till the end of the follow-up period (mean, 56.7 months).
- Researchers also investigated the common infectious sites, the etiology of the infection, vaccination status, variables associated with lung function, and clinical-therapeutic variables associated with RA.
TAKEAWAY:
- During the follow-up period, almost all (96%) patients had at least one infection, with the median time to first infection being 21.2 months and 65% of the deaths being directly related to infections.
- Respiratory infections were the most common first infections (74%) and led to death in 80% of the patients. Urinary tract (9.9%) and skin and soft tissue (9.1%) infections were the second and third most common first infections, respectively.
- Most infections were caused by SARS-CoV-2 (33.5%), Streptococcus pneumoniae (11.9%), Escherichia coli (11.9%), and Pseudomonas aeruginosa (11.1%), with mortality at 25.8% for SARS-CoV-2, 12.9% for P aeruginosa (12.9%), and 9.6% for pneumococci (9.6%).
- Increased age, disease activity, and the use of corticosteroids were associated with an elevated risk for infection and mortality in patients with RA-ILD.
IN PRACTICE:
“Our results demonstrate a high occurrence of serious infections among these patients, occurring early, recurring frequently, and proving fatal in 65% of cases,” the authors wrote.
SOURCE:
This study was led by Natalia Mena-Vázquez, MD, PhD, from Instituto de Investigación Biomédica de Málaga-Plataforma Bionand, Málaga, Spain, and published online March 27 in Frontiers in Immunology.
LIMITATIONS:
The findings of this study have been affected by the COVID-19 pandemic. The lack of a control group also limited the ability of this study to establish any causal relationships between ILD and the clinical outcomes analyzed.
DISCLOSURE:
This study was supported by Redes de Investigación Cooperativa Orientadas a Resultados en Salud and Fundación Andaluza de Reumatología. The authors declared having no conflicts of interest.
A version of this article appeared on Medscape.com.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>Patients with rheumatoid arthritis–associated interstitial lung disease (RA-ILD) have a high risk for serious and fatal infections, with age, inflammation, and </metaDescription> <articlePDF/> <teaserImage/> <teaser>Patients with RA-associated ILD found to have increased risk for serious infections, 65% of them fatal, study finds.</teaser> <title>High Infection Risk in Rheumatoid Arthritis–Associated Interstitial Lung Disease</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>chph</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>rn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">6</term> <term>26</term> <term>15</term> <term>21</term> </publications> <sections> <term canonical="true">39313</term> </sections> <topics> <term canonical="true">289</term> <term>284</term> <term>290</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>High Infection Risk in Rheumatoid Arthritis–Associated Interstitial Lung Disease</title> <deck/> </itemMeta> <itemContent> <h2>TOPLINE:</h2> <p> <span class="tag metaDescription">Patients with <span class="Hyperlink">rheumatoid arthritis</span>–associated interstitial lung disease (RA-ILD) have a high risk for serious and fatal infections, with age, inflammation, and corticosteroid therapy further increasing this risk.</span> </p> <h2>METHODOLOGY:</h2> <ul class="body"> <li>Patients with RA who have extra-articular manifestations such as ILD are highly susceptible to infections, but information on the types of infections, risk factors, and associations of infections with hospitalization and mortality is limited.</li> <li>This prospective multicenter cohort study evaluated infections in a cohort of 148 patients with RA-ILD (average age, 70 years; 57% women) recruited from 11 university hospitals in Spain between March 2015 and March 2023.</li> <li>Joint, lung, and any infection-related variables were evaluated using clinical and laboratory evaluations at baseline and selected time points till the end of the follow-up period (mean, 56.7 months).</li> <li>Researchers also investigated the common infectious sites, the etiology of the infection, vaccination status, variables associated with lung function, and clinical-therapeutic variables associated with RA.</li> </ul> <h2>TAKEAWAY:</h2> <ul class="body"> <li>During the follow-up period, almost all (96%) patients had at least one infection, with the median time to first infection being 21.2 months and 65% of the deaths being directly related to infections.</li> <li><span class="Hyperlink">Respiratory infections</span> were the most common first infections (74%) and led to death in 80% of the patients. Urinary tract (9.9%) and skin and soft tissue (9.1%) infections were the second and third most common first infections, respectively.</li> <li>Most infections were caused by SARS-CoV-2 (33.5%), <em>Streptococcus pneumoniae</em> (11.9%), <em>Escherichia coli</em> (11.9%), and <em>Pseudomonas aeruginosa</em> (11.1%), with mortality at 25.8% for SARS-CoV-2, 12.9% for <em>P aeruginosa</em> (12.9%), and 9.6% for pneumococci (9.6%).</li> <li>Increased age, disease activity, and the use of corticosteroids were associated with an elevated risk for infection and mortality in patients with RA-ILD.</li> </ul> <h2>IN PRACTICE:</h2> <p>“Our results demonstrate a high occurrence of serious infections among these patients, occurring early, recurring frequently, and proving fatal in 65% of cases,” the authors wrote.</p> <h2>SOURCE:</h2> <p>This study was led by Natalia Mena-Vázquez, MD, PhD, from Instituto de Investigación Biomédica de Málaga-Plataforma Bionand, Málaga, Spain, and <span class="Hyperlink"><a href="https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1341321/full">published online</a></span> March 27 in <em>Frontiers in Immunology</em>.</p> <h2>LIMITATIONS:</h2> <p>The findings of this study have been affected by the COVID-19 pandemic. The lack of a control group also limited the ability of this study to establish any causal relationships between ILD and the clinical outcomes analyzed.</p> <h2>DISCLOSURE:</h2> <p>This study was supported by Redes de Investigación Cooperativa Orientadas a Resultados en Salud and Fundación Andaluza de Reumatología. The authors declared having no conflicts of interest.<br/><br/></p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/high-infection-risk-rheumatoid-arthritis-associated-2024a10006zr?src=">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
Congress Directly Provides $10 Million for Arthritis Research for First Time
Congress provided $10 million to fund arthritis research in the recently passed federal fiscal year 2024 budget.
The new arthritis program is part of the Department of Defense’s (DOD’s) Congressionally Directed Medical Research Programs (CDMRP), which provides dedicated funding to study certain diseases and health conditions.
This is the first stand-alone research program for arthritis of the CDMRP, though the organization had previously funded arthritis-related research through their other programs, including chronic pain management, joint warfighter medical, peer-reviewed orthopedic, peer-reviewed medical, and tick-borne disease programs.
It is not yet known what specific aspects of arthritis this funding will go toward. The standard process for new programs involves speaking with researchers, clinicians, and individuals with these targeted health conditions to better understand research gaps and narrow focus, Akua Roach, PhD, the program manager for this new CDMRP arthritis research program, told this news organization.
“We’re not going to be able to solve every question,” she said, though the allocated $10 million is “a great number to do a lot of great work.”
While the CDMRP is under the DOD, research funding can go to studying patient populations outside of military personnel or veterans, she added.
“I think that is perhaps a common misconception that if you are getting funding from the DOD, that you have to have a DOD population, and that is not true,” she said.
Another misconception is that CDMRP funding only goes to military treatment facilities. In fact, on average, 92% of CDMRP funding goes to academia, industry, and other nonmilitary recipients, noted CDMRP Director Colonel Sarah Goldman.
“Anyone around the world can apply for funding,” she told this news organization. “We want to fund the best research.”
Because the funding is provided under the defense bill, there will be discussions around the military relevance of research, she added, which not only includes service members but also their families.
CDMRP anticipates that funding opportunities through this new arthritis research program will be available by July or August 2024.
A version of this article appeared on Medscape.com.
Congress provided $10 million to fund arthritis research in the recently passed federal fiscal year 2024 budget.
The new arthritis program is part of the Department of Defense’s (DOD’s) Congressionally Directed Medical Research Programs (CDMRP), which provides dedicated funding to study certain diseases and health conditions.
This is the first stand-alone research program for arthritis of the CDMRP, though the organization had previously funded arthritis-related research through their other programs, including chronic pain management, joint warfighter medical, peer-reviewed orthopedic, peer-reviewed medical, and tick-borne disease programs.
It is not yet known what specific aspects of arthritis this funding will go toward. The standard process for new programs involves speaking with researchers, clinicians, and individuals with these targeted health conditions to better understand research gaps and narrow focus, Akua Roach, PhD, the program manager for this new CDMRP arthritis research program, told this news organization.
“We’re not going to be able to solve every question,” she said, though the allocated $10 million is “a great number to do a lot of great work.”
While the CDMRP is under the DOD, research funding can go to studying patient populations outside of military personnel or veterans, she added.
“I think that is perhaps a common misconception that if you are getting funding from the DOD, that you have to have a DOD population, and that is not true,” she said.
Another misconception is that CDMRP funding only goes to military treatment facilities. In fact, on average, 92% of CDMRP funding goes to academia, industry, and other nonmilitary recipients, noted CDMRP Director Colonel Sarah Goldman.
“Anyone around the world can apply for funding,” she told this news organization. “We want to fund the best research.”
Because the funding is provided under the defense bill, there will be discussions around the military relevance of research, she added, which not only includes service members but also their families.
CDMRP anticipates that funding opportunities through this new arthritis research program will be available by July or August 2024.
A version of this article appeared on Medscape.com.
Congress provided $10 million to fund arthritis research in the recently passed federal fiscal year 2024 budget.
The new arthritis program is part of the Department of Defense’s (DOD’s) Congressionally Directed Medical Research Programs (CDMRP), which provides dedicated funding to study certain diseases and health conditions.
This is the first stand-alone research program for arthritis of the CDMRP, though the organization had previously funded arthritis-related research through their other programs, including chronic pain management, joint warfighter medical, peer-reviewed orthopedic, peer-reviewed medical, and tick-borne disease programs.
It is not yet known what specific aspects of arthritis this funding will go toward. The standard process for new programs involves speaking with researchers, clinicians, and individuals with these targeted health conditions to better understand research gaps and narrow focus, Akua Roach, PhD, the program manager for this new CDMRP arthritis research program, told this news organization.
“We’re not going to be able to solve every question,” she said, though the allocated $10 million is “a great number to do a lot of great work.”
While the CDMRP is under the DOD, research funding can go to studying patient populations outside of military personnel or veterans, she added.
“I think that is perhaps a common misconception that if you are getting funding from the DOD, that you have to have a DOD population, and that is not true,” she said.
Another misconception is that CDMRP funding only goes to military treatment facilities. In fact, on average, 92% of CDMRP funding goes to academia, industry, and other nonmilitary recipients, noted CDMRP Director Colonel Sarah Goldman.
“Anyone around the world can apply for funding,” she told this news organization. “We want to fund the best research.”
Because the funding is provided under the defense bill, there will be discussions around the military relevance of research, she added, which not only includes service members but also their families.
CDMRP anticipates that funding opportunities through this new arthritis research program will be available by July or August 2024.
A version of this article appeared on Medscape.com.
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>167618</fileName> <TBEID>0C04F797.SIG</TBEID> <TBUniqueIdentifier>MD_0C04F797</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname/> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20240408T163938</QCDate> <firstPublished>20240408T164223</firstPublished> <LastPublished>20240408T164223</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240408T164223</CMSDate> <articleSource/> <facebookInfo/> <meetingNumber/> <byline>Lucy Hicks</byline> <bylineText>LUCY HICKS</bylineText> <bylineFull>LUCY HICKS</bylineFull> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType>News</newsDocType> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>Congress provided $10 million to fund arthritis research in the recently passed federal fiscal year 2024 budget.</metaDescription> <articlePDF/> <teaserImage>192337</teaserImage> <teaser>This is the first stand-alone arthritis research program under the Department of Defenses’ Congressionally Directed Medical Research Programs.</teaser> <title>Congress Directly Provides $10 Million for Arthritis Research for First Time</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>rn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">26</term> <term>21</term> </publications> <sections> <term canonical="true">39313</term> </sections> <topics> <term>38029</term> <term>282</term> <term>289</term> <term canonical="true">265</term> <term>183</term> <term>299</term> <term>290</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24007085.jpg</altRep> <description role="drol:caption"/> <description role="drol:credit">Lucidology/Thinkstock</description> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Congress Directly Provides $10 Million for Arthritis Research for First Time</title> <deck/> </itemMeta> <itemContent> <p>Congress provided $10 million to fund arthritis research in the recently passed federal fiscal year 2024 budget.</p> <p>The new arthritis program is part of the Department of Defense’s (DOD’s) Congressionally Directed Medical Research Programs (CDMRP), which provides dedicated funding to study certain diseases and health conditions.<br/><br/>This is the first stand-alone research program for arthritis of the CDMRP, though the organization had previously funded arthritis-related research through their other programs, including chronic pain management, joint warfighter medical, peer-reviewed orthopedic, peer-reviewed medical, and <span class="Hyperlink">tick-borne disease</span> programs.<br/><br/>[[{"fid":"192337","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"A stethoscope placed on paper money atop an American flag","field_file_image_credit[und][0][value]":"Lucidology/Thinkstock","field_file_image_caption[und][0][value]":""},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]It is not yet known what specific aspects of arthritis this funding will go toward. The standard process for new programs involves speaking with researchers, clinicians, and individuals with these targeted health conditions to better understand research gaps and narrow focus, Akua Roach, PhD, the program manager for this new CDMRP arthritis research program, told this news organization.<br/><br/>“We’re not going to be able to solve every question,” she said, though the allocated $10 million is “a great number to do a lot of great work.”<br/><br/>While the CDMRP is under the DOD, research funding can go to studying patient populations outside of military personnel or veterans, she added.<br/><br/>“I think that is perhaps a common misconception that if you are getting funding from the DOD, that you have to have a DOD population, and that is not true,” she said.<br/><br/>Another misconception is that CDMRP funding only goes to military treatment facilities. In fact, on average, 92% of CDMRP funding goes to academia, industry, and other nonmilitary recipients, noted CDMRP Director Colonel Sarah Goldman.<br/><br/>“Anyone around the world can apply for funding,” she told this news organization. “We want to fund the best research.”<br/><br/>Because the funding is provided under the defense bill, there will be discussions around the military relevance of research, she added, which not only includes service members but also their families.<br/><br/>CDMRP anticipates that funding opportunities through this new arthritis research program will be available by July or August 2024.<br/><br/></p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/congress-allocates-10-million-arthritis-research-2024a10006lg">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
Tuberculosis Screening Gaps Persist in New DMARD Users
TOPLINE:
The rates of screening for latent tuberculosis remain suboptimal among new users of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), with notable variations by medication type and demographic characteristics.
METHODOLOGY:
- Professional society guidelines recommend screening for tuberculosis before starting treatment with most b/tsDMARDs.
- In an attempt to estimate the extent of latent tuberculosis screening, researchers combined claims and electronic health record datasets to evaluate 2853 new b/tsDMARD users (mean age, 73 years; 72% women; and 73% non-Hispanic White).
- The primary analysis focused on assessing the proportion of patients screened for latent tuberculosis in the year before starting a new b/tsDMARD.
- A sensitivity analysis evaluated the extent of screening within the 3 years preceding the initiation of a new b/tsDMARD.
- A total of 65.6% of patients received screening for latent tuberculosis in the year before initiating a new b/tsDMARD.
- Screening rates improved only slightly on expanding the window to 3 years, with 72.9% of patients receiving any tuberculosis screening.
- When stratified by drug type, over half of new users of Janus kinase inhibitors and nearly 90% of new users of interleukin-17 inhibitors had not received screening.
- Hispanic patients had lower odds of tuberculosis screening within 1 year than White patients (odds ratio [OR], 0.64; 95% CI, 0.46-0.90), as did those in the highest socioeconomic quartile, compared with the lowest (OR, 0.61; 95% CI, 0.40-0.94).
IN PRACTICE:
“Educational initiatives, team-based care delivery, task shifting, and technological interventions to address observed gaps in patient safety procedures are needed,” the authors wrote.
SOURCE:
The study was led by Eric T. Roberts, PhD, University of California, San Francisco, and published online in Arthritis Care & Research
LIMITATIONS:
The study lacked access to scanned documents or clinical notes, which may have resulted in the omission of a small number of tests that had no Medicare billing. Moreover, the study was restricted to a 3-year lookback period, potentially missing some remote screenings. The findings may have limited generalizability to younger patients or those not dually eligible for Medicare and Medicaid.
DISCLOSURES:
This study was funded by grants from the Agency for Healthcare Research and Quality and the National Institute for Arthritis and Musculoskeletal and Skin Diseases. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
The rates of screening for latent tuberculosis remain suboptimal among new users of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), with notable variations by medication type and demographic characteristics.
METHODOLOGY:
- Professional society guidelines recommend screening for tuberculosis before starting treatment with most b/tsDMARDs.
- In an attempt to estimate the extent of latent tuberculosis screening, researchers combined claims and electronic health record datasets to evaluate 2853 new b/tsDMARD users (mean age, 73 years; 72% women; and 73% non-Hispanic White).
- The primary analysis focused on assessing the proportion of patients screened for latent tuberculosis in the year before starting a new b/tsDMARD.
- A sensitivity analysis evaluated the extent of screening within the 3 years preceding the initiation of a new b/tsDMARD.
- A total of 65.6% of patients received screening for latent tuberculosis in the year before initiating a new b/tsDMARD.
- Screening rates improved only slightly on expanding the window to 3 years, with 72.9% of patients receiving any tuberculosis screening.
- When stratified by drug type, over half of new users of Janus kinase inhibitors and nearly 90% of new users of interleukin-17 inhibitors had not received screening.
- Hispanic patients had lower odds of tuberculosis screening within 1 year than White patients (odds ratio [OR], 0.64; 95% CI, 0.46-0.90), as did those in the highest socioeconomic quartile, compared with the lowest (OR, 0.61; 95% CI, 0.40-0.94).
IN PRACTICE:
“Educational initiatives, team-based care delivery, task shifting, and technological interventions to address observed gaps in patient safety procedures are needed,” the authors wrote.
SOURCE:
The study was led by Eric T. Roberts, PhD, University of California, San Francisco, and published online in Arthritis Care & Research
LIMITATIONS:
The study lacked access to scanned documents or clinical notes, which may have resulted in the omission of a small number of tests that had no Medicare billing. Moreover, the study was restricted to a 3-year lookback period, potentially missing some remote screenings. The findings may have limited generalizability to younger patients or those not dually eligible for Medicare and Medicaid.
DISCLOSURES:
This study was funded by grants from the Agency for Healthcare Research and Quality and the National Institute for Arthritis and Musculoskeletal and Skin Diseases. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
The rates of screening for latent tuberculosis remain suboptimal among new users of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), with notable variations by medication type and demographic characteristics.
METHODOLOGY:
- Professional society guidelines recommend screening for tuberculosis before starting treatment with most b/tsDMARDs.
- In an attempt to estimate the extent of latent tuberculosis screening, researchers combined claims and electronic health record datasets to evaluate 2853 new b/tsDMARD users (mean age, 73 years; 72% women; and 73% non-Hispanic White).
- The primary analysis focused on assessing the proportion of patients screened for latent tuberculosis in the year before starting a new b/tsDMARD.
- A sensitivity analysis evaluated the extent of screening within the 3 years preceding the initiation of a new b/tsDMARD.
- A total of 65.6% of patients received screening for latent tuberculosis in the year before initiating a new b/tsDMARD.
- Screening rates improved only slightly on expanding the window to 3 years, with 72.9% of patients receiving any tuberculosis screening.
- When stratified by drug type, over half of new users of Janus kinase inhibitors and nearly 90% of new users of interleukin-17 inhibitors had not received screening.
- Hispanic patients had lower odds of tuberculosis screening within 1 year than White patients (odds ratio [OR], 0.64; 95% CI, 0.46-0.90), as did those in the highest socioeconomic quartile, compared with the lowest (OR, 0.61; 95% CI, 0.40-0.94).
IN PRACTICE:
“Educational initiatives, team-based care delivery, task shifting, and technological interventions to address observed gaps in patient safety procedures are needed,” the authors wrote.
SOURCE:
The study was led by Eric T. Roberts, PhD, University of California, San Francisco, and published online in Arthritis Care & Research
LIMITATIONS:
The study lacked access to scanned documents or clinical notes, which may have resulted in the omission of a small number of tests that had no Medicare billing. Moreover, the study was restricted to a 3-year lookback period, potentially missing some remote screenings. The findings may have limited generalizability to younger patients or those not dually eligible for Medicare and Medicaid.
DISCLOSURES:
This study was funded by grants from the Agency for Healthcare Research and Quality and the National Institute for Arthritis and Musculoskeletal and Skin Diseases. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>The rates of screening for latent tuberculosis remain suboptimal among new users of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsD</metaDescription> <articlePDF/> <teaserImage/> <teaser>Substantial patient safety gaps regarding latent tuberculosis screening persist among new users of biologic or targeted synthetic DMARDs, suggested a nationwide cohort study.</teaser> <title>Tuberculosis Screening Gaps Persist in New DMARD Users</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>rn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">26</term> <term>21</term> <term>15</term> </publications> <sections> <term canonical="true">27970</term> <term>39313</term> </sections> <topics> <term canonical="true">289</term> <term>299</term> <term>282</term> <term>241</term> <term>183</term> <term>290</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Tuberculosis Screening Gaps Persist in New DMARD Users</title> <deck/> </itemMeta> <itemContent> <h2>TOPLINE:</h2> <p>The rates of screening for latent <a href="https://emedicine.medscape.com/article/230802-overview">tuberculosis</a> remain suboptimal among new users of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), with notable variations by medication type and demographic characteristics. </p> <h2>METHODOLOGY:</h2> <ul class="body"> <li>Professional society guidelines recommend screening for tuberculosis before starting treatment with most b/tsDMARDs.</li> <li>In an attempt to estimate the extent of latent tuberculosis screening, researchers combined claims and electronic health record datasets to evaluate 2853 new b/tsDMARD users (mean age, 73 years; 72% women; and 73% non-Hispanic White).</li> <li>The primary analysis focused on assessing the proportion of patients screened for latent tuberculosis in the year before starting a new b/tsDMARD.</li> <li>A sensitivity analysis evaluated the extent of screening within the 3 years preceding the initiation of a new b/tsDMARD.</li> <li>A total of 65.6% of patients received screening for latent tuberculosis in the year before initiating a new b/tsDMARD.</li> <li>Screening rates improved only slightly on expanding the window to 3 years, with 72.9% of patients receiving any tuberculosis screening.</li> <li>When stratified by drug type, over half of new users of Janus kinase inhibitors and nearly 90% of new users of interleukin-17 inhibitors had not received screening.</li> <li>Hispanic patients had lower odds of tuberculosis screening within 1 year than White patients (odds ratio [OR], 0.64; 95% CI, 0.46-0.90), as did those in the highest socioeconomic quartile, compared with the lowest (OR, 0.61; 95% CI, 0.40-0.94).</li> </ul> <h2>IN PRACTICE:</h2> <p>“Educational initiatives, team-based care delivery, task shifting, and technological interventions to address observed gaps in patient safety procedures are needed,” the authors wrote.</p> <h2>SOURCE:</h2> <p>The study was led by Eric T. Roberts, PhD, University of California, San Francisco, and <a href="https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/acr.25318">published online</a> in <em>Arthritis Care & Research</em></p> <h2>LIMITATIONS:</h2> <p>The study lacked access to scanned documents or clinical notes, which may have resulted in the omission of a small number of tests that had no Medicare billing. Moreover, the study was restricted to a 3-year lookback period, potentially missing some remote screenings. The findings may have limited generalizability to younger patients or those not dually eligible for Medicare and Medicaid.</p> <h2>DISCLOSURES:</h2> <p>This study was funded by grants from the Agency for Healthcare Research and Quality and the National Institute for Arthritis and Musculoskeletal and Skin Diseases. The authors declared no conflicts of interest.<span class="end"/></p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/tuberculosis-screening-gaps-persist-new-dmard-users-2024a100067l?src=">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
Autoimmunity’s Female Bias and the Mysteries of Xist
Female bias in autoimmune disease can be profound, with nine females developing lupus for every male affected, and nearly twice that ratio seen in Sjögren disease.
For years, researchers have worked to determine the reasons for sex-linked differences in immune response and autoimmunity, with environmental factors, sex hormones, and X-chromosome inactivation — the process by which a second X chromosome is silenced — all seen as having roles.
More recently, different groups of researchers have homed in on a long noncoding RNA fragment called X-inactive specific transcript, or Xist, as a potential driver of sex bias in autoimmune disease. Xist, which occurs in female mammals, has been known since the 1990s as the master regulator of X-chromosome inactivation, the process by which the second X chromosome is silenced, averting a fatal double dose of X-linked genes.
The inactivation process, which scientists liken to wrapping the extra X with a fluffy cloud of proteins, occurs early in embryonic development. After its initial work silencing the X, Xist is produced throughout the female’s life, allowing X inactivation to be maintained.
But is it possible that Xist, and the many dozens of proteins it recruits to keep that extra X chromosome silent, can also provoke autoimmunity? This is the question that several teams of researchers have been grappling with, resulting in provocative findings and opening exciting new avenues of discovery.
Xist Protein Complexes Make Male Mice Vulnerable to Lupus
In February, researchers Howard Chang, MD, PhD, and Diana Dou, PhD, of Stanford University in Stanford, California, made worldwide news when they published results from an experiment using male mice genetically engineered to carry a non-silencing form of Xist on one of their chromosomes.
Xist acts like a scaffold, recruiting multiple protein complexes to help it do its job. Dr. Dou explained in an interview that her team has been eyeing suspiciously for years the dozens of proteins Xist recruits in the process of X-chromosome inactivation, many of which are known autoantigens.
When the mice were injected with pristane, a chemical that induces lupus-like autoimmunity in mice, the Xist-producing males developed symptoms at a rate similar to that of females, while wild-type male mice did not.
By using a male model, the scientists could determine whether Xist could cause an increased vulnerability for autoimmunity absent the influence of female hormones and development. “Everything else about the animal is male,” Dr. Dou commented. “You just add the formation of the Xist ribonucleoprotein particles — Xist RNA plus the associating proteins — to male cells that would not ordinarily have these particles. Is just having the particles present in these animals sufficient to increase their autoimmunity? This is what our paper showed: That just having expression of Xist, the presence of these Xist [ribonucleoproteins], is enough in permissive genetic backgrounds to invoke higher incidence and severity of autoimmune disease development in our pristane-induced lupus model.”
The Stanford group sees the Xist protein complex, which they have studied extensively, as a key to understanding how Xist might provoke autoimmunity. Nonetheless, Dr. Dou said, “It’s important to note that there are other contributing factors, which is why not all females develop autoimmunity, and we had very different results in our autoimmune-resistant mouse strain compared to the more autoimmune-prone strain. Xist is a factor, but many factors are required to subvert the checkpoints in immune balance and allow the progression to full-blown autoimmunity.”
Faulty X Inactivation and Gene Escape
The understanding that Xist might be implicated in autoimmune disease — and explain some of its female bias — is not new.
About a decade ago, Montserrat Anguera, PhD, a biologist at the University of Pennsylvania, Philadelphia, began looking at the relationship of X-chromosome inactivation, which by definition involves Xist, and lupus.
Dr. Anguera hypothesized that imperfect X inactivation allowed for greater escape of genes associated with immunity and autoimmunity. Studying patients with lupus, Dr. Anguera found that the silencing process was abnormal, allowing more of these genes to escape the silenced X — including toll-like receptor 7 (TLR-7) and other genes implicated in the pathogenesis of lupus.
“If you get increased expression of certain genes from the [silenced] X, like TLR-7, it can result in autoimmune disease,” Dr. Anguera said. “So what we think is that in the lupus patients, because the silencing is impacted, you’re going to have more expression happening from the inactive X. And then in conjunction with the active X, that’s going to throw off the dosage [of autoimmunity-linked genes]. You’re changing the dosage of genes, and that’s what’s critical.”
Even among patients with lupus whose symptoms are well controlled with medication, “if you look at their T cells and B cells, they still have messed up X inactivation,” Dr. Anguera said. “The Xist RNA that’s supposed to be tethered to the inactive X in a fluffy cloud is not localized, and instead is dispersed all over the nucleus.”
Dr. Anguera pointed out that autoimmune diseases are complex and can result from a combination of factors. “You also have a host of hormonal and environmental contributors, such as previous viral infections,” she said. And of course men can also develop lupus, meaning that the X chromosome cannot explain everything.
Dr. Anguera said that, while the findings by the Stanford scientists do not explain the full pathogenesis of lupus and related diseases, they still support a strong role for Xist in sex-biased autoimmune diseases. “It’s sort of another take on it,” she said.
Is It the Proteins, the RNA, or Both?
The Stanford team points to the proteins recruited by Xist in the process of X-chromosome inactivation as the likely trigger of autoimmunity. However, a group of researchers at Johns Hopkins University in Baltimore, Maryland, made the case in a 2022 paper that Xist RNA itself was dangerous. They found that numerous short RNA sequences within the Xist molecule serve as ligands for TLR-7. And TLR-7 ligation causes plasmacytoid dendritic cells to overproduce type 1 interferon, a classic hallmark of lupus.
“Within rheumatology, the diseases that tend to be most female biased are the ones that are antibody positive and have this presence of upregulated interferon,” explained Brendan Antiochos, MD. “Lupus is an example of that. Sjögren’s syndrome is another. So there’s always been this quest to want to understand the mechanisms that explain why women would have more autoimmunity. And are there specific pathways which could contribute? One of the key pathways that’s been shown in humans and in mice to be important in lupus is toll-like receptor signaling.” Most convincingly, one recent study showed that people who have a gain-of-function mutation in their TLR-7 gene get a spontaneous form of lupus.
These findings led Erika Darrah, PhD, and her colleague Dr. Antiochos to begin looking more deeply into which RNAs could be triggering this signaling pathway. “We started to think: Well, there is this sex bias. Could it be that women have unique RNAs that could potentially act as triggers for TLR-7 signaling?” Dr. Darrah said.
Dr. Darrah and Dr. Antiochos looked at publicly available genetic data to identify sex-biased sources of self-RNA containing TLR-7 ligands. Xist, they found, was chock full of them. “Every time we analyzed that data, no matter what filter we applied, Xist kept popping out over and over again as the most highly female skewed RNA, the RNA most likely to contain these TLR-7 binding motifs,” Dr. Darrah said. “We started to formulate the hypothesis that Xist was actually promoting responses that were dangerous and pathogenic in lupus.”
That finding led the team to conduct in-vitro experiments that showed different fragments of Xist can activate TLR-7, resulting in higher interferon production. Finally, they looked at blood and kidney cells from women with lupus and found that higher Xist expression correlated with more interferon production, and higher disease activity. “The more Xist, the sicker people were,” Dr. Darrah said.
Xist’s Other Functions
Xist was first studied in the 1990s, and most research has centered on its primary role in X-chromosome inactivation. A research group led by Kathrin Plath, PhD, at the University of California, Los Angeles, has been occupied for years with untangling exactly how Xist does what it does. “It’s a very clever RNA, right? It can silence the whole chromosome,” Dr. Plath said in an interview.
In 2021, Dr. Plath and her colleagues established in detail how Xist executes silencing, setting down pairs of molecules in specific spots along the chromosome and building huge protein clouds around them. “We worked on learning where Xist binds and what proteins it binds, drilling down to understand how these proteins and the RNA are coming together.”
Dr. Plath has long suspected that Xist has other functions besides X inactivation, and she and her colleagues are starting to identify them. Early this year they published the surprising finding that Xist can regulate gene expression in autosomes, or non–sex-linked chromosomes, “which it might well also do in cancer cells and lymphocytes,” Dr. Plath said. “And now there is this new evidence of an autoimmune function,” she said. “It’s a super exciting time.”
The different hypotheses surrounding Xist’s role in sex-biased autoimmunity aren’t mutually exclusive, Dr. Plath said. “There’s a tremendous enrichment of proteins occurring” during X inactivation, she said, supporting the Stanford team’s hypothesis that proteins are triggering autoimmunity. As for the Johns Hopkins researchers’ understanding that Xist RNA itself is the trigger, “I’m totally open to that,” she said. “Why can’t it be an autoantigen?”
The other model in the field, Dr. Plath noted, is the one proposed by Dr. Anguera — “that there’s [gene] escape from X-inactivation — that females have more escape expression, and that Xist is more dispersed in the lymphocytes [of patients with lupus]. In fact, Xist becoming a little dispersed might make it a better antigen. So I do think everything is possible.”
The plethora of new findings related to autoimmunity has caused Dr. Plath to consider redirecting her lab’s focus toward more translational work, “because we are obviously good at studying Xist.” Among the mysteries Dr. Plath would like to solve is how some genes manage to escape the Xist cloud.
What is needed, she said, is collaboration. “Everyone will come up with different ideas. So I think it’s good to have more people look at things together. Then the field will achieve a breakthrough treatment.”
Female bias in autoimmune disease can be profound, with nine females developing lupus for every male affected, and nearly twice that ratio seen in Sjögren disease.
For years, researchers have worked to determine the reasons for sex-linked differences in immune response and autoimmunity, with environmental factors, sex hormones, and X-chromosome inactivation — the process by which a second X chromosome is silenced — all seen as having roles.
More recently, different groups of researchers have homed in on a long noncoding RNA fragment called X-inactive specific transcript, or Xist, as a potential driver of sex bias in autoimmune disease. Xist, which occurs in female mammals, has been known since the 1990s as the master regulator of X-chromosome inactivation, the process by which the second X chromosome is silenced, averting a fatal double dose of X-linked genes.
The inactivation process, which scientists liken to wrapping the extra X with a fluffy cloud of proteins, occurs early in embryonic development. After its initial work silencing the X, Xist is produced throughout the female’s life, allowing X inactivation to be maintained.
But is it possible that Xist, and the many dozens of proteins it recruits to keep that extra X chromosome silent, can also provoke autoimmunity? This is the question that several teams of researchers have been grappling with, resulting in provocative findings and opening exciting new avenues of discovery.
Xist Protein Complexes Make Male Mice Vulnerable to Lupus
In February, researchers Howard Chang, MD, PhD, and Diana Dou, PhD, of Stanford University in Stanford, California, made worldwide news when they published results from an experiment using male mice genetically engineered to carry a non-silencing form of Xist on one of their chromosomes.
Xist acts like a scaffold, recruiting multiple protein complexes to help it do its job. Dr. Dou explained in an interview that her team has been eyeing suspiciously for years the dozens of proteins Xist recruits in the process of X-chromosome inactivation, many of which are known autoantigens.
When the mice were injected with pristane, a chemical that induces lupus-like autoimmunity in mice, the Xist-producing males developed symptoms at a rate similar to that of females, while wild-type male mice did not.
By using a male model, the scientists could determine whether Xist could cause an increased vulnerability for autoimmunity absent the influence of female hormones and development. “Everything else about the animal is male,” Dr. Dou commented. “You just add the formation of the Xist ribonucleoprotein particles — Xist RNA plus the associating proteins — to male cells that would not ordinarily have these particles. Is just having the particles present in these animals sufficient to increase their autoimmunity? This is what our paper showed: That just having expression of Xist, the presence of these Xist [ribonucleoproteins], is enough in permissive genetic backgrounds to invoke higher incidence and severity of autoimmune disease development in our pristane-induced lupus model.”
The Stanford group sees the Xist protein complex, which they have studied extensively, as a key to understanding how Xist might provoke autoimmunity. Nonetheless, Dr. Dou said, “It’s important to note that there are other contributing factors, which is why not all females develop autoimmunity, and we had very different results in our autoimmune-resistant mouse strain compared to the more autoimmune-prone strain. Xist is a factor, but many factors are required to subvert the checkpoints in immune balance and allow the progression to full-blown autoimmunity.”
Faulty X Inactivation and Gene Escape
The understanding that Xist might be implicated in autoimmune disease — and explain some of its female bias — is not new.
About a decade ago, Montserrat Anguera, PhD, a biologist at the University of Pennsylvania, Philadelphia, began looking at the relationship of X-chromosome inactivation, which by definition involves Xist, and lupus.
Dr. Anguera hypothesized that imperfect X inactivation allowed for greater escape of genes associated with immunity and autoimmunity. Studying patients with lupus, Dr. Anguera found that the silencing process was abnormal, allowing more of these genes to escape the silenced X — including toll-like receptor 7 (TLR-7) and other genes implicated in the pathogenesis of lupus.
“If you get increased expression of certain genes from the [silenced] X, like TLR-7, it can result in autoimmune disease,” Dr. Anguera said. “So what we think is that in the lupus patients, because the silencing is impacted, you’re going to have more expression happening from the inactive X. And then in conjunction with the active X, that’s going to throw off the dosage [of autoimmunity-linked genes]. You’re changing the dosage of genes, and that’s what’s critical.”
Even among patients with lupus whose symptoms are well controlled with medication, “if you look at their T cells and B cells, they still have messed up X inactivation,” Dr. Anguera said. “The Xist RNA that’s supposed to be tethered to the inactive X in a fluffy cloud is not localized, and instead is dispersed all over the nucleus.”
Dr. Anguera pointed out that autoimmune diseases are complex and can result from a combination of factors. “You also have a host of hormonal and environmental contributors, such as previous viral infections,” she said. And of course men can also develop lupus, meaning that the X chromosome cannot explain everything.
Dr. Anguera said that, while the findings by the Stanford scientists do not explain the full pathogenesis of lupus and related diseases, they still support a strong role for Xist in sex-biased autoimmune diseases. “It’s sort of another take on it,” she said.
Is It the Proteins, the RNA, or Both?
The Stanford team points to the proteins recruited by Xist in the process of X-chromosome inactivation as the likely trigger of autoimmunity. However, a group of researchers at Johns Hopkins University in Baltimore, Maryland, made the case in a 2022 paper that Xist RNA itself was dangerous. They found that numerous short RNA sequences within the Xist molecule serve as ligands for TLR-7. And TLR-7 ligation causes plasmacytoid dendritic cells to overproduce type 1 interferon, a classic hallmark of lupus.
“Within rheumatology, the diseases that tend to be most female biased are the ones that are antibody positive and have this presence of upregulated interferon,” explained Brendan Antiochos, MD. “Lupus is an example of that. Sjögren’s syndrome is another. So there’s always been this quest to want to understand the mechanisms that explain why women would have more autoimmunity. And are there specific pathways which could contribute? One of the key pathways that’s been shown in humans and in mice to be important in lupus is toll-like receptor signaling.” Most convincingly, one recent study showed that people who have a gain-of-function mutation in their TLR-7 gene get a spontaneous form of lupus.
These findings led Erika Darrah, PhD, and her colleague Dr. Antiochos to begin looking more deeply into which RNAs could be triggering this signaling pathway. “We started to think: Well, there is this sex bias. Could it be that women have unique RNAs that could potentially act as triggers for TLR-7 signaling?” Dr. Darrah said.
Dr. Darrah and Dr. Antiochos looked at publicly available genetic data to identify sex-biased sources of self-RNA containing TLR-7 ligands. Xist, they found, was chock full of them. “Every time we analyzed that data, no matter what filter we applied, Xist kept popping out over and over again as the most highly female skewed RNA, the RNA most likely to contain these TLR-7 binding motifs,” Dr. Darrah said. “We started to formulate the hypothesis that Xist was actually promoting responses that were dangerous and pathogenic in lupus.”
That finding led the team to conduct in-vitro experiments that showed different fragments of Xist can activate TLR-7, resulting in higher interferon production. Finally, they looked at blood and kidney cells from women with lupus and found that higher Xist expression correlated with more interferon production, and higher disease activity. “The more Xist, the sicker people were,” Dr. Darrah said.
Xist’s Other Functions
Xist was first studied in the 1990s, and most research has centered on its primary role in X-chromosome inactivation. A research group led by Kathrin Plath, PhD, at the University of California, Los Angeles, has been occupied for years with untangling exactly how Xist does what it does. “It’s a very clever RNA, right? It can silence the whole chromosome,” Dr. Plath said in an interview.
In 2021, Dr. Plath and her colleagues established in detail how Xist executes silencing, setting down pairs of molecules in specific spots along the chromosome and building huge protein clouds around them. “We worked on learning where Xist binds and what proteins it binds, drilling down to understand how these proteins and the RNA are coming together.”
Dr. Plath has long suspected that Xist has other functions besides X inactivation, and she and her colleagues are starting to identify them. Early this year they published the surprising finding that Xist can regulate gene expression in autosomes, or non–sex-linked chromosomes, “which it might well also do in cancer cells and lymphocytes,” Dr. Plath said. “And now there is this new evidence of an autoimmune function,” she said. “It’s a super exciting time.”
The different hypotheses surrounding Xist’s role in sex-biased autoimmunity aren’t mutually exclusive, Dr. Plath said. “There’s a tremendous enrichment of proteins occurring” during X inactivation, she said, supporting the Stanford team’s hypothesis that proteins are triggering autoimmunity. As for the Johns Hopkins researchers’ understanding that Xist RNA itself is the trigger, “I’m totally open to that,” she said. “Why can’t it be an autoantigen?”
The other model in the field, Dr. Plath noted, is the one proposed by Dr. Anguera — “that there’s [gene] escape from X-inactivation — that females have more escape expression, and that Xist is more dispersed in the lymphocytes [of patients with lupus]. In fact, Xist becoming a little dispersed might make it a better antigen. So I do think everything is possible.”
The plethora of new findings related to autoimmunity has caused Dr. Plath to consider redirecting her lab’s focus toward more translational work, “because we are obviously good at studying Xist.” Among the mysteries Dr. Plath would like to solve is how some genes manage to escape the Xist cloud.
What is needed, she said, is collaboration. “Everyone will come up with different ideas. So I think it’s good to have more people look at things together. Then the field will achieve a breakthrough treatment.”
Female bias in autoimmune disease can be profound, with nine females developing lupus for every male affected, and nearly twice that ratio seen in Sjögren disease.
For years, researchers have worked to determine the reasons for sex-linked differences in immune response and autoimmunity, with environmental factors, sex hormones, and X-chromosome inactivation — the process by which a second X chromosome is silenced — all seen as having roles.
More recently, different groups of researchers have homed in on a long noncoding RNA fragment called X-inactive specific transcript, or Xist, as a potential driver of sex bias in autoimmune disease. Xist, which occurs in female mammals, has been known since the 1990s as the master regulator of X-chromosome inactivation, the process by which the second X chromosome is silenced, averting a fatal double dose of X-linked genes.
The inactivation process, which scientists liken to wrapping the extra X with a fluffy cloud of proteins, occurs early in embryonic development. After its initial work silencing the X, Xist is produced throughout the female’s life, allowing X inactivation to be maintained.
But is it possible that Xist, and the many dozens of proteins it recruits to keep that extra X chromosome silent, can also provoke autoimmunity? This is the question that several teams of researchers have been grappling with, resulting in provocative findings and opening exciting new avenues of discovery.
Xist Protein Complexes Make Male Mice Vulnerable to Lupus
In February, researchers Howard Chang, MD, PhD, and Diana Dou, PhD, of Stanford University in Stanford, California, made worldwide news when they published results from an experiment using male mice genetically engineered to carry a non-silencing form of Xist on one of their chromosomes.
Xist acts like a scaffold, recruiting multiple protein complexes to help it do its job. Dr. Dou explained in an interview that her team has been eyeing suspiciously for years the dozens of proteins Xist recruits in the process of X-chromosome inactivation, many of which are known autoantigens.
When the mice were injected with pristane, a chemical that induces lupus-like autoimmunity in mice, the Xist-producing males developed symptoms at a rate similar to that of females, while wild-type male mice did not.
By using a male model, the scientists could determine whether Xist could cause an increased vulnerability for autoimmunity absent the influence of female hormones and development. “Everything else about the animal is male,” Dr. Dou commented. “You just add the formation of the Xist ribonucleoprotein particles — Xist RNA plus the associating proteins — to male cells that would not ordinarily have these particles. Is just having the particles present in these animals sufficient to increase their autoimmunity? This is what our paper showed: That just having expression of Xist, the presence of these Xist [ribonucleoproteins], is enough in permissive genetic backgrounds to invoke higher incidence and severity of autoimmune disease development in our pristane-induced lupus model.”
The Stanford group sees the Xist protein complex, which they have studied extensively, as a key to understanding how Xist might provoke autoimmunity. Nonetheless, Dr. Dou said, “It’s important to note that there are other contributing factors, which is why not all females develop autoimmunity, and we had very different results in our autoimmune-resistant mouse strain compared to the more autoimmune-prone strain. Xist is a factor, but many factors are required to subvert the checkpoints in immune balance and allow the progression to full-blown autoimmunity.”
Faulty X Inactivation and Gene Escape
The understanding that Xist might be implicated in autoimmune disease — and explain some of its female bias — is not new.
About a decade ago, Montserrat Anguera, PhD, a biologist at the University of Pennsylvania, Philadelphia, began looking at the relationship of X-chromosome inactivation, which by definition involves Xist, and lupus.
Dr. Anguera hypothesized that imperfect X inactivation allowed for greater escape of genes associated with immunity and autoimmunity. Studying patients with lupus, Dr. Anguera found that the silencing process was abnormal, allowing more of these genes to escape the silenced X — including toll-like receptor 7 (TLR-7) and other genes implicated in the pathogenesis of lupus.
“If you get increased expression of certain genes from the [silenced] X, like TLR-7, it can result in autoimmune disease,” Dr. Anguera said. “So what we think is that in the lupus patients, because the silencing is impacted, you’re going to have more expression happening from the inactive X. And then in conjunction with the active X, that’s going to throw off the dosage [of autoimmunity-linked genes]. You’re changing the dosage of genes, and that’s what’s critical.”
Even among patients with lupus whose symptoms are well controlled with medication, “if you look at their T cells and B cells, they still have messed up X inactivation,” Dr. Anguera said. “The Xist RNA that’s supposed to be tethered to the inactive X in a fluffy cloud is not localized, and instead is dispersed all over the nucleus.”
Dr. Anguera pointed out that autoimmune diseases are complex and can result from a combination of factors. “You also have a host of hormonal and environmental contributors, such as previous viral infections,” she said. And of course men can also develop lupus, meaning that the X chromosome cannot explain everything.
Dr. Anguera said that, while the findings by the Stanford scientists do not explain the full pathogenesis of lupus and related diseases, they still support a strong role for Xist in sex-biased autoimmune diseases. “It’s sort of another take on it,” she said.
Is It the Proteins, the RNA, or Both?
The Stanford team points to the proteins recruited by Xist in the process of X-chromosome inactivation as the likely trigger of autoimmunity. However, a group of researchers at Johns Hopkins University in Baltimore, Maryland, made the case in a 2022 paper that Xist RNA itself was dangerous. They found that numerous short RNA sequences within the Xist molecule serve as ligands for TLR-7. And TLR-7 ligation causes plasmacytoid dendritic cells to overproduce type 1 interferon, a classic hallmark of lupus.
“Within rheumatology, the diseases that tend to be most female biased are the ones that are antibody positive and have this presence of upregulated interferon,” explained Brendan Antiochos, MD. “Lupus is an example of that. Sjögren’s syndrome is another. So there’s always been this quest to want to understand the mechanisms that explain why women would have more autoimmunity. And are there specific pathways which could contribute? One of the key pathways that’s been shown in humans and in mice to be important in lupus is toll-like receptor signaling.” Most convincingly, one recent study showed that people who have a gain-of-function mutation in their TLR-7 gene get a spontaneous form of lupus.
These findings led Erika Darrah, PhD, and her colleague Dr. Antiochos to begin looking more deeply into which RNAs could be triggering this signaling pathway. “We started to think: Well, there is this sex bias. Could it be that women have unique RNAs that could potentially act as triggers for TLR-7 signaling?” Dr. Darrah said.
Dr. Darrah and Dr. Antiochos looked at publicly available genetic data to identify sex-biased sources of self-RNA containing TLR-7 ligands. Xist, they found, was chock full of them. “Every time we analyzed that data, no matter what filter we applied, Xist kept popping out over and over again as the most highly female skewed RNA, the RNA most likely to contain these TLR-7 binding motifs,” Dr. Darrah said. “We started to formulate the hypothesis that Xist was actually promoting responses that were dangerous and pathogenic in lupus.”
That finding led the team to conduct in-vitro experiments that showed different fragments of Xist can activate TLR-7, resulting in higher interferon production. Finally, they looked at blood and kidney cells from women with lupus and found that higher Xist expression correlated with more interferon production, and higher disease activity. “The more Xist, the sicker people were,” Dr. Darrah said.
Xist’s Other Functions
Xist was first studied in the 1990s, and most research has centered on its primary role in X-chromosome inactivation. A research group led by Kathrin Plath, PhD, at the University of California, Los Angeles, has been occupied for years with untangling exactly how Xist does what it does. “It’s a very clever RNA, right? It can silence the whole chromosome,” Dr. Plath said in an interview.
In 2021, Dr. Plath and her colleagues established in detail how Xist executes silencing, setting down pairs of molecules in specific spots along the chromosome and building huge protein clouds around them. “We worked on learning where Xist binds and what proteins it binds, drilling down to understand how these proteins and the RNA are coming together.”
Dr. Plath has long suspected that Xist has other functions besides X inactivation, and she and her colleagues are starting to identify them. Early this year they published the surprising finding that Xist can regulate gene expression in autosomes, or non–sex-linked chromosomes, “which it might well also do in cancer cells and lymphocytes,” Dr. Plath said. “And now there is this new evidence of an autoimmune function,” she said. “It’s a super exciting time.”
The different hypotheses surrounding Xist’s role in sex-biased autoimmunity aren’t mutually exclusive, Dr. Plath said. “There’s a tremendous enrichment of proteins occurring” during X inactivation, she said, supporting the Stanford team’s hypothesis that proteins are triggering autoimmunity. As for the Johns Hopkins researchers’ understanding that Xist RNA itself is the trigger, “I’m totally open to that,” she said. “Why can’t it be an autoantigen?”
The other model in the field, Dr. Plath noted, is the one proposed by Dr. Anguera — “that there’s [gene] escape from X-inactivation — that females have more escape expression, and that Xist is more dispersed in the lymphocytes [of patients with lupus]. In fact, Xist becoming a little dispersed might make it a better antigen. So I do think everything is possible.”
The plethora of new findings related to autoimmunity has caused Dr. Plath to consider redirecting her lab’s focus toward more translational work, “because we are obviously good at studying Xist.” Among the mysteries Dr. Plath would like to solve is how some genes manage to escape the Xist cloud.
What is needed, she said, is collaboration. “Everyone will come up with different ideas. So I think it’s good to have more people look at things together. Then the field will achieve a breakthrough treatment.”
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>167534</fileName> <TBEID>0C04F5BD.SIG</TBEID> <TBUniqueIdentifier>MD_0C04F5BD</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname/> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20240402T153106</QCDate> <firstPublished>20240402T153332</firstPublished> <LastPublished>20240402T153332</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240402T153332</CMSDate> <articleSource/> <facebookInfo/> <meetingNumber/> <byline>Jennie Smith</byline> <bylineText>JENNIE SMITH</bylineText> <bylineFull>JENNIE SMITH</bylineFull> <bylineTitleText>MDedge News</bylineTitleText> <USOrGlobal/> <wireDocType/> <newsDocType>Feature</newsDocType> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>Female bias in autoimmune disease can be profound, with nine females developing lupus for every male affected, and nearly twice that ratio seen in Sjögren disea</metaDescription> <articlePDF/> <teaserImage>300967</teaserImage> <teaser>Researchers are homing in on a long non-coding RNA, essential to X chromosome inactivation, as the culprit in sex-biased autoimmune diseases like lupus. While there are different theories as to how Xist causes harm, and much left to be learned, the findings offer hope for new treatment targets and approaches.</teaser> <title>Autoimmunity’s Female Bias and the Mysteries of Xist</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>rn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>pn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>nr</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> <journalTitle>Neurology Reviews</journalTitle> <journalFullTitle>Neurology Reviews</journalFullTitle> <copyrightStatement>2018 Frontline Medical Communications Inc.,</copyrightStatement> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>skin</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">26</term> <term>25</term> <term>22</term> <term>21</term> <term>15</term> <term>13</term> </publications> <sections> <term canonical="true">27980</term> <term>39313</term> </sections> <topics> <term canonical="true">241</term> <term>289</term> <term>285</term> <term>251</term> <term>290</term> <term>322</term> <term>231</term> <term>29134</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/240127c7.jpg</altRep> <description role="drol:caption">Dr. Diana Dou</description> <description role="drol:credit"/> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/240127c9.jpg</altRep> <description role="drol:caption">Dr. Montserrat Anguera</description> <description role="drol:credit">University of Pennsylvania</description> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/240127c5.jpg</altRep> <description role="drol:caption">Johns Hopkins University researchers studying Xist (left to right): Daniela Trejo-Zambrano, Jonathan Crawford, Erika Darrah, Brendan Antiochos, Hong Wang</description> <description role="drol:credit">Alexander Girgis</description> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/240127c6.jpg</altRep> <description role="drol:caption">Dr. Erika Darrah</description> <description role="drol:credit">Wes Linda</description> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/240127c8.jpg</altRep> <description role="drol:caption">Dr. Kathrin Plath</description> <description role="drol:credit"/> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Autoimmunity’s Female Bias and the Mysteries of Xist</title> <deck/> </itemMeta> <itemContent> <p>Female bias in autoimmune disease can be profound, with nine females developing lupus for every male affected, and nearly twice that ratio seen in Sjögren disease. </p> <p>For years, researchers have worked to determine the reasons for sex-linked differences in immune response and autoimmunity, with environmental factors, sex hormones, and X-chromosome inactivation — the process by which a second X chromosome is silenced — all seen as having roles.<br/><br/>More recently, different groups of researchers have homed in on a long noncoding RNA fragment called X-inactive specific transcript, or Xist, as a potential driver of sex bias in autoimmune disease. Xist, which occurs in female mammals, has been known since the 1990s as the master regulator of X-chromosome inactivation, the process by which the second X chromosome is silenced, averting a fatal double dose of X-linked genes. <br/><br/>The inactivation process, which scientists liken to wrapping the extra X with a fluffy cloud of proteins, occurs early in embryonic development. After its initial work silencing the X, Xist is produced throughout the female’s life, allowing X inactivation to be maintained. <br/><br/>But is it possible that Xist, and the many dozens of proteins it recruits to keep that extra X chromosome silent, can also provoke autoimmunity? This is the question that several teams of researchers have been grappling with, resulting in provocative findings and opening exciting new avenues of discovery. <br/><br/></p> <h2>Xist Protein Complexes Make Male Mice Vulnerable to Lupus</h2> <p>In February, researchers <span class="Hyperlink"><a href="https://profiles.stanford.edu/howard-chang?tab=teaching">Howard Chang, MD, PhD</a></span>, and <span class="Hyperlink"><a href="https://profiles.stanford.edu/diana-dou">Diana Dou, PhD</a></span>, of Stanford University in Stanford, California, made worldwide news when they <span class="Hyperlink"><a href="https://www.cell.com/cell/fulltext/S0092-8674(24)00002-3">published results</a></span> from an experiment using male mice genetically engineered to carry a non-silencing form of Xist on one of their chromosomes.</p> <p>[[{"fid":"300967","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Diana Dou of Stanford University in Stanford, California","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"Dr. Diana Dou"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]Xist acts like a scaffold, recruiting multiple protein complexes to help it do its job. Dr. Dou explained in an interview that her team has been eyeing suspiciously for years the dozens of proteins Xist recruits in the process of X-chromosome inactivation, many of which are known autoantigens.<br/><br/>When the mice were injected with pristane, a chemical that induces lupus-like autoimmunity in mice, the Xist-producing males developed symptoms at a rate similar to that of females, while wild-type male mice did not.<br/><br/>By using a male model, the scientists could determine whether Xist could cause an increased vulnerability for autoimmunity absent the influence of female hormones and development. “Everything else about the animal is male,” Dr. Dou commented. “You just add the formation of the Xist ribonucleoprotein particles — Xist RNA plus the associating proteins — to male cells that would not ordinarily have these particles. Is just having the particles present in these animals sufficient to increase their autoimmunity? This is what our paper showed: That just having expression of Xist, the presence of these Xist [ribonucleoproteins], is enough in permissive genetic backgrounds to invoke higher incidence and severity of autoimmune disease development in our pristane-induced lupus model.”<br/><br/>The Stanford group sees the Xist protein complex, which they have <span class="Hyperlink"><a href="https://www.nature.com/articles/s41467-020-20040-3">studied extensively</a></span>, as a key to understanding how Xist might provoke autoimmunity. Nonetheless, Dr. Dou said, “It’s important to note that there are other contributing factors, which is why not all females develop autoimmunity, and we had very different results in our autoimmune-resistant mouse strain compared to the more autoimmune-prone strain. Xist is a factor, but many factors are required to subvert the checkpoints in immune balance and allow the progression to full-blown autoimmunity.”<br/><br/></p> <h2>Faulty X Inactivation and Gene Escape </h2> <p>The understanding that Xist might be implicated in autoimmune disease — and explain some of its female bias — is not new. </p> <p>About a decade ago, <span class="Hyperlink"><a href="https://www.vet.upenn.edu/people/faculty-clinician-search/MONTSERRATANGUERA">Montserrat Anguera, PhD</a></span>, a biologist at the University of Pennsylvania, Philadelphia, began looking at the relationship of X-chromosome inactivation, which by definition involves Xist, and lupus. <br/><br/>[[{"fid":"300970","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. Montserrat Anguera, a biologist at the University of Pennsylvania, Philadelphia","field_file_image_credit[und][0][value]":"University of Pennsylvania","field_file_image_caption[und][0][value]":"Dr. Montserrat Anguera"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]Dr. Anguera hypothesized that imperfect X inactivation allowed for greater escape of genes associated with immunity and autoimmunity. Studying patients with lupus, Dr. Anguera found that the <span class="Hyperlink"><a href="https://www.pnas.org/doi/full/10.1073/pnas.2024624118">silencing process was abnormal</a></span>, allowing more of these genes to escape the silenced X — including toll-like receptor 7 (TLR-7) and other genes implicated in the pathogenesis of lupus.<br/><br/>“If you get increased expression of certain genes from the [silenced] X, like TLR-7, it can result in autoimmune disease,” Dr. Anguera said. “So what we think is that in the lupus patients, because the silencing is impacted, you’re going to have more expression happening from the inactive X. And then in conjunction with the active X, that’s going to throw off the dosage [of autoimmunity-linked genes]. You’re changing the dosage of genes, and that’s what’s critical.”<br/><br/>Even among patients with lupus whose symptoms are well controlled with medication, “if you look at their T cells and B cells, they still have messed up X inactivation,” Dr. Anguera said. “The Xist RNA that’s supposed to be tethered to the inactive X in a fluffy cloud is not localized, and instead is dispersed all over the nucleus.”<br/><br/>Dr. Anguera pointed out that autoimmune diseases are complex and can result from a combination of factors. “You also have a host of hormonal and environmental contributors, such as previous viral infections,” she said. And of course men can also develop lupus, meaning that the X chromosome cannot explain everything. <br/><br/>Dr. Anguera said that, while the findings by the Stanford scientists do not explain the full pathogenesis of lupus and related diseases, they still support a strong role for Xist in sex-biased autoimmune diseases. “It’s sort of another take on it,” she said.<br/><br/></p> <h2>Is It the Proteins, the RNA, or Both? </h2> <p>The Stanford team points to the proteins recruited by Xist in the process of X-chromosome inactivation as the likely trigger of autoimmunity. However, a group of researchers at Johns Hopkins University in Baltimore, Maryland, made the case in a <span class="Hyperlink"><a href="https://journals.aai.org/jimmunol/article/208/1_Supplement/108.02/236370/XIST-is-a-source-of-TLR7-ligands-underlying-the">2022 paper</a></span> that Xist RNA itself was dangerous. They found that numerous short RNA sequences within the Xist molecule serve as ligands for TLR-7. And TLR-7 ligation causes plasmacytoid dendritic cells to overproduce type 1 interferon, a classic hallmark of lupus.</p> <p>[[{"fid":"300968","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Johns Hopkins University researchers studying Xist (left to right): Daniela Trejo-Zambrano, Jonathan Crawford, Erika Darrah, Brendan Antiochos, Hong Wang.","field_file_image_credit[und][0][value]":"Alexander Girgis","field_file_image_caption[und][0][value]":"Johns Hopkins University researchers studying Xist (left to right): Daniela Trejo-Zambrano, Jonathan Crawford, Erika Darrah, Brendan Antiochos, Hong Wang"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]“Within rheumatology, the diseases that tend to be most female biased are the ones that are antibody positive and have this presence of upregulated interferon,” explained <span class="Hyperlink"><a href="https://www.hopkinsmedicine.org/profiles/details/brendan-antiochos">Brendan Antiochos, MD</a></span>. “Lupus is an example of that. Sjögren’s syndrome is another. So there’s always been this quest to want to understand the mechanisms that explain why women would have more autoimmunity. And are there specific pathways which could contribute? One of the key pathways that’s been shown in humans and in mice to be important in lupus is toll-like receptor signaling.” Most convincingly, <span class="Hyperlink"><a href="https://www.nature.com/articles/s41586-022-04642-z">one recent study</a></span> <span class="Hyperlink">showed</span> that people who have a gain-of-function mutation in their TLR-7 gene get a spontaneous form of lupus. <br/><br/>[[{"fid":"300966","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Erika Darrah, Assistant Professor in the Division of Rheumatology at Johns Hopkins University, Baltimore, Maryland","field_file_image_credit[und][0][value]":"Wes Linda","field_file_image_caption[und][0][value]":"Dr. Erika Darrah"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]These findings led <span class="Hyperlink"><a href="https://gradimmunology.med.som.jhmi.edu/darrah/">Erika Darrah, PhD</a></span>, and her colleague Dr. Antiochos to begin looking more deeply into which RNAs could be triggering this signaling pathway. “We started to think: Well, there is this sex bias. Could it be that women have unique RNAs that could potentially act as triggers for TLR-7 signaling?” Dr. Darrah said. <br/><br/>Dr. Darrah and Dr. Antiochos looked at publicly available genetic data to identify sex-biased sources of self-RNA containing TLR-7 ligands.<span class="apple-converted-space"> Xist, they found, was chock full of them. “</span>Every time we analyzed that data, no matter what filter we applied, Xist kept popping out over and over again as the most highly female skewed RNA, the RNA most likely to contain these TLR-7 binding motifs,” Dr. Darrah said. “We started to formulate the hypothesis that Xist was actually promoting responses that were dangerous and pathogenic in lupus.” <br/><br/>That finding led the team to conduct in-vitro experiments that showed different fragments of Xist can activate TLR-7, resulting in higher interferon production. Finally, they looked at blood and kidney cells from women with lupus and found that higher Xist expression correlated with more interferon production, and higher disease activity. “The more Xist, the sicker people were,” Dr. Darrah said. <br/><br/></p> <h2>Xist’s Other Functions</h2> <p>Xist was first studied in the 1990s, and most research has centered on its primary role in X-chromosome inactivation. A research group led by <span class="Hyperlink"><a href="https://www.biolchem.ucla.edu/people/kathrin-plath/">Kathrin Plath, PhD</a></span>, at the University of California, Los Angeles, has been occupied for years with untangling exactly how Xist does what it does. “It’s a very clever RNA, right? It can silence the whole chromosome,” Dr. Plath said in an interview. </p> <p>[[{"fid":"300969","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. Kathrin Plath of the University of California, Los Angeles","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"Dr. Kathrin Plath"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]In 2021, Dr. Plath and her colleagues established in detail <span class="Hyperlink"><a href="https://www.cell.com/cell/fulltext/S0092-8674(21)01275-7">how Xist executes silencing</a></span>, setting down pairs of molecules in specific spots along the chromosome and building huge protein clouds around them. “We worked on learning where Xist binds and what proteins it binds, drilling down to understand how these proteins and the RNA are coming together.”<br/><br/>Dr. Plath has long suspected that Xist has other functions besides X inactivation, and she and her colleagues are starting to identify them. Early this year they published the surprising finding that Xist can <span class="Hyperlink"><a href="https://www.cell.com/cell/fulltext/S0092-8674(23)01319-3">regulate gene expression in autosomes</a></span>, or non–sex-linked chromosomes, “which it might well also do in cancer cells and lymphocytes,” Dr. Plath said. “And now there is this new evidence of an autoimmune function,” she said. “It’s a super exciting time.”<br/><br/>The different hypotheses surrounding Xist’s role in sex-biased autoimmunity aren’t mutually exclusive, Dr. Plath said. “There’s a tremendous enrichment of proteins occurring” during X inactivation, she said, supporting the Stanford team’s hypothesis that proteins are triggering autoimmunity. As for the Johns Hopkins researchers’ understanding that Xist RNA itself is the trigger, “I’m totally open to that,” she said. “Why can’t it be an autoantigen?”<br/><br/>The other model in the field, Dr. Plath noted, is the one proposed by Dr. Anguera — “that there’s [gene] escape from X-inactivation — that females have more escape expression, and that Xist is more dispersed in the lymphocytes [of patients with lupus]. In fact, Xist becoming a little dispersed might make it a better antigen. So I do think everything is possible.”<br/><br/>The plethora of new findings related to autoimmunity has caused Dr. Plath to consider redirecting her lab’s focus toward more translational work, “because we are obviously good at studying Xist.” Among the mysteries Dr. Plath would like to solve is how some genes manage to escape the Xist cloud. <br/><br/>What is needed, she said, is collaboration. “Everyone will come up with different ideas. So I think it’s good to have more people look at things together. Then the field will achieve a breakthrough treatment.”<span class="end"/></p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
