Thomas R. Collins

ORLANDO – When he was applying for residency, Omar N. Qutub, MD, eagerly arrived at his first interview of the day. But he was quickly thrown off his game.

The interviewer, he said, spent a surprising amount of time asking about his ethnicity and his last name. “I think I spent about 3-5 minutes in the first interview talking about my last name,” said Dr. Qutub, who practices in Portland, Ore., during a session titled “unconscious bias and microaggressions in dermatology” at the ODAC Dermatology, Aesthetic and Surgical Conference. “I really would have rather talked about my research interests.” The interaction threw him off for the rest of the interview process, he said.

Qutub_Omar_N_OR_web.jpg

The experience is an example of how the field has a ways to go in acquiring cultural competence and in overcoming unconscious biases, said Dr. Qutub. In 2020, a review in Clinics in Dermatology referred to a report that dermatology was the second-least diverse medical specialty, only behind orthopedic surgery, because of its low numbers of residents and faculty from groups underrepresented in medicine.

“We really need to put cultural competency at the forefront in order to do better for our patients,” he said.

Friedman_Adam_WASHINGTON_web.jpg

Adam Friedman, MD, professor and chair of dermatology and director of the residency program at George Washington University, Washington, who also spoke during the session, said that the process of diversifying the field has to go deeper than the resident interviewing process. “If we just focus on trying to increase the diversity of our applicant pool for residents, it’s too late.”

Nada Elbuluk, MD, associate professor of dermatology at the University of Southern California, Los Angeles, pointed to USC’s Derm RISES initiative, a service program that aims to reach inner-city students through education in the sciences, starting from kindergarten to 12th grade. The program also includes premed undergraduate and medical students, “with the goal of increasing exposure to the sciences, medicine, and dermatology,” according to the USC website. “It’s crucial to begin the process early to get a high yield of students who reach medical school and eventually dermatology, she said, because of the inevitable attrition at each level of the education process.

Elbuluk_Nada_CA_2022_web.jpg

“It’s incredibly rewarding,” added Dr. Elbuluk, who is also director of the dermatology diversity and inclusion program at USC. “And we get these thank-you letters back from students who [say], ‘I didn’t know I could be a doctor.’ ”

In another presentation, Kavita Mariwalla, MD, who practices in West Islip, N.Y., provided tips on boosting cultural competence during aesthetic consults.

One was to “know your fillers,” she said, noting that fillers have different effects on different skin tones, because of differences in fibroblast content, and fat cells will interact with fillers in different ways across skin tones.

Another is to “understand the shortfall of facial canons,” the idea that you can divide a face into sections that can be viewed and enhanced discretely. This concept was based on a White European model and has to be expanded when considering other ethnicities, Dr. Mariwalla said.

Overgeneralizing categories is another pitfall, she said. “Asian” is a term that covers countries from India to Japan, but within that category are a multitude of notions and nuances about aesthetics, and dermatologists have to be sensitive to all of them.

[embed:render:related:node:259841]

When meeting with a patient, Dr. Mariwalla said, asking the typical “Where are you from?” is not a helpful question. Instead, she suggested asking: “What is your cultural background? Can you tell me more about what your expectations are?”

“I ask for pictures,” she said. “I want to know what they looked like as a kid. I want to know what their family looks like. And I always hand patients a mirror. Patients will say to me: ‘I want to do what you think.’ It’s not about what I think, because what I see, and what you see in your magnifying mirror, are totally different things.”

After the session ended, a member of the audience, Sharon Stokes, MD, a dermatologist in the Orlando area, provided her view of the presentations, noting that it was an important discussion.

“I think it’s past time in medicine for cultural diversity training and awareness for physicians to understand their patients better and getting to know them – and how to even approach the patient and not to offensively and microaggressively approach the patient,” she said.

Dr. Elbuluk reported relevant relationships with Avita, Incyte, Beiersdorf, and other companies. Dr. Friedman reported financial relationships with Sanova, Pfizer, Novartis and other companies. Dr. Mariwalla reported relevant financial relationships with Abbvie, Sanofi, Regeneron and other companies. Dr. Qutub reported no relevant financial relationships. Dr. Qutub is the ODAC director of equity, diversity, and inclusion.

ORLANDO – When he was applying for residency, Omar N. Qutub, MD, eagerly arrived at his first interview of the day. But he was quickly thrown off his game.

The interviewer, he said, spent a surprising amount of time asking about his ethnicity and his last name. “I think I spent about 3-5 minutes in the first interview talking about my last name,” said Dr. Qutub, who practices in Portland, Ore., during a session titled “unconscious bias and microaggressions in dermatology” at the ODAC Dermatology, Aesthetic and Surgical Conference. “I really would have rather talked about my research interests.” The interaction threw him off for the rest of the interview process, he said.

Qutub_Omar_N_OR_web.jpg

The experience is an example of how the field has a ways to go in acquiring cultural competence and in overcoming unconscious biases, said Dr. Qutub. In 2020, a review in Clinics in Dermatology referred to a report that dermatology was the second-least diverse medical specialty, only behind orthopedic surgery, because of its low numbers of residents and faculty from groups underrepresented in medicine.

“We really need to put cultural competency at the forefront in order to do better for our patients,” he said.

Friedman_Adam_WASHINGTON_web.jpg

Adam Friedman, MD, professor and chair of dermatology and director of the residency program at George Washington University, Washington, who also spoke during the session, said that the process of diversifying the field has to go deeper than the resident interviewing process. “If we just focus on trying to increase the diversity of our applicant pool for residents, it’s too late.”

Nada Elbuluk, MD, associate professor of dermatology at the University of Southern California, Los Angeles, pointed to USC’s Derm RISES initiative, a service program that aims to reach inner-city students through education in the sciences, starting from kindergarten to 12th grade. The program also includes premed undergraduate and medical students, “with the goal of increasing exposure to the sciences, medicine, and dermatology,” according to the USC website. “It’s crucial to begin the process early to get a high yield of students who reach medical school and eventually dermatology, she said, because of the inevitable attrition at each level of the education process.

Elbuluk_Nada_CA_2022_web.jpg

“It’s incredibly rewarding,” added Dr. Elbuluk, who is also director of the dermatology diversity and inclusion program at USC. “And we get these thank-you letters back from students who [say], ‘I didn’t know I could be a doctor.’ ”

In another presentation, Kavita Mariwalla, MD, who practices in West Islip, N.Y., provided tips on boosting cultural competence during aesthetic consults.

One was to “know your fillers,” she said, noting that fillers have different effects on different skin tones, because of differences in fibroblast content, and fat cells will interact with fillers in different ways across skin tones.

Another is to “understand the shortfall of facial canons,” the idea that you can divide a face into sections that can be viewed and enhanced discretely. This concept was based on a White European model and has to be expanded when considering other ethnicities, Dr. Mariwalla said.

Overgeneralizing categories is another pitfall, she said. “Asian” is a term that covers countries from India to Japan, but within that category are a multitude of notions and nuances about aesthetics, and dermatologists have to be sensitive to all of them.

[embed:render:related:node:259841]

When meeting with a patient, Dr. Mariwalla said, asking the typical “Where are you from?” is not a helpful question. Instead, she suggested asking: “What is your cultural background? Can you tell me more about what your expectations are?”

“I ask for pictures,” she said. “I want to know what they looked like as a kid. I want to know what their family looks like. And I always hand patients a mirror. Patients will say to me: ‘I want to do what you think.’ It’s not about what I think, because what I see, and what you see in your magnifying mirror, are totally different things.”

After the session ended, a member of the audience, Sharon Stokes, MD, a dermatologist in the Orlando area, provided her view of the presentations, noting that it was an important discussion.

“I think it’s past time in medicine for cultural diversity training and awareness for physicians to understand their patients better and getting to know them – and how to even approach the patient and not to offensively and microaggressively approach the patient,” she said.

Dr. Elbuluk reported relevant relationships with Avita, Incyte, Beiersdorf, and other companies. Dr. Friedman reported financial relationships with Sanova, Pfizer, Novartis and other companies. Dr. Mariwalla reported relevant financial relationships with Abbvie, Sanofi, Regeneron and other companies. Dr. Qutub reported no relevant financial relationships. Dr. Qutub is the ODAC director of equity, diversity, and inclusion.

ORLANDO – When he was applying for residency, Omar N. Qutub, MD, eagerly arrived at his first interview of the day. But he was quickly thrown off his game.

The interviewer, he said, spent a surprising amount of time asking about his ethnicity and his last name. “I think I spent about 3-5 minutes in the first interview talking about my last name,” said Dr. Qutub, who practices in Portland, Ore., during a session titled “unconscious bias and microaggressions in dermatology” at the ODAC Dermatology, Aesthetic and Surgical Conference. “I really would have rather talked about my research interests.” The interaction threw him off for the rest of the interview process, he said.

Qutub_Omar_N_OR_web.jpg

The experience is an example of how the field has a ways to go in acquiring cultural competence and in overcoming unconscious biases, said Dr. Qutub. In 2020, a review in Clinics in Dermatology referred to a report that dermatology was the second-least diverse medical specialty, only behind orthopedic surgery, because of its low numbers of residents and faculty from groups underrepresented in medicine.

“We really need to put cultural competency at the forefront in order to do better for our patients,” he said.

Friedman_Adam_WASHINGTON_web.jpg

Adam Friedman, MD, professor and chair of dermatology and director of the residency program at George Washington University, Washington, who also spoke during the session, said that the process of diversifying the field has to go deeper than the resident interviewing process. “If we just focus on trying to increase the diversity of our applicant pool for residents, it’s too late.”

Nada Elbuluk, MD, associate professor of dermatology at the University of Southern California, Los Angeles, pointed to USC’s Derm RISES initiative, a service program that aims to reach inner-city students through education in the sciences, starting from kindergarten to 12th grade. The program also includes premed undergraduate and medical students, “with the goal of increasing exposure to the sciences, medicine, and dermatology,” according to the USC website. “It’s crucial to begin the process early to get a high yield of students who reach medical school and eventually dermatology, she said, because of the inevitable attrition at each level of the education process.

Elbuluk_Nada_CA_2022_web.jpg

“It’s incredibly rewarding,” added Dr. Elbuluk, who is also director of the dermatology diversity and inclusion program at USC. “And we get these thank-you letters back from students who [say], ‘I didn’t know I could be a doctor.’ ”

In another presentation, Kavita Mariwalla, MD, who practices in West Islip, N.Y., provided tips on boosting cultural competence during aesthetic consults.

One was to “know your fillers,” she said, noting that fillers have different effects on different skin tones, because of differences in fibroblast content, and fat cells will interact with fillers in different ways across skin tones.

Another is to “understand the shortfall of facial canons,” the idea that you can divide a face into sections that can be viewed and enhanced discretely. This concept was based on a White European model and has to be expanded when considering other ethnicities, Dr. Mariwalla said.

Overgeneralizing categories is another pitfall, she said. “Asian” is a term that covers countries from India to Japan, but within that category are a multitude of notions and nuances about aesthetics, and dermatologists have to be sensitive to all of them.

[embed:render:related:node:259841]

When meeting with a patient, Dr. Mariwalla said, asking the typical “Where are you from?” is not a helpful question. Instead, she suggested asking: “What is your cultural background? Can you tell me more about what your expectations are?”

“I ask for pictures,” she said. “I want to know what they looked like as a kid. I want to know what their family looks like. And I always hand patients a mirror. Patients will say to me: ‘I want to do what you think.’ It’s not about what I think, because what I see, and what you see in your magnifying mirror, are totally different things.”

After the session ended, a member of the audience, Sharon Stokes, MD, a dermatologist in the Orlando area, provided her view of the presentations, noting that it was an important discussion.

“I think it’s past time in medicine for cultural diversity training and awareness for physicians to understand their patients better and getting to know them – and how to even approach the patient and not to offensively and microaggressively approach the patient,” she said.

Dr. Elbuluk reported relevant relationships with Avita, Incyte, Beiersdorf, and other companies. Dr. Friedman reported financial relationships with Sanova, Pfizer, Novartis and other companies. Dr. Mariwalla reported relevant financial relationships with Abbvie, Sanofi, Regeneron and other companies. Dr. Qutub reported no relevant financial relationships. Dr. Qutub is the ODAC director of equity, diversity, and inclusion.

The American Gastroenterological Association has made the first investment through its new venture capital fund – an initiative that gives gastroenterologists a financial opportunity combined with a chance to help corporations trying to make a difference in the field.

The fund – called the GI Opportunity Fund 1 – invests in fast-growing, early-stage companies, with the goal of hastening innovation that could ultimately help patients with digestive diseases. It was established in partnership with Varia Ventures.

The AGA recently announced the fund’s first investment with Carlsbad, Calif.–based Virgo Surgical Video Solutions, which offers endoscopy video recording that uses artificial intelligence for ease of use during procedures, for reviewing video later, and for using video to connect trial investigators with potential candidates.

Kosinski_Lawrence_2022_web.JPG

“While AGA has long guided innovators who share our goal of improving digestive health care, we have doubled down on this commitment by establishing the GI Opportunity Fund,” said Lawrence Kosinski, MD, AGAF, AGA Governing Board Councilor for Development and Growth. “The fund’s first investment – Virgo – exemplifies our pursuit of improved clinical care.”

He said the fund gives physicians a chance to work closely with AGA to invest in difference-making ventures.

“Through our venture fund, gastroenterologists can join AGA to invest in fast-growing, early-stage companies that are transforming care for patients with digestive disease,” Dr. Kosinski said.

Schwartz_Matthew_web.jpg

Virgo CEO Matthew Z. Schwartz said the company’s product is intended to fill an important need.

“We recognized that it was really difficult for doctors to capture endoscopy procedures video in high-definition at scale,” he said. “Generally, they were just taking still images. And the images were often not of great quality.”

Virgo offers a small device that connects to existing endoscopy equipment, plugging into the back of a video processor, securely compressing and encrypting video and sending it to Virgo’s HIPAA-compliant cloud storage Web portal. Once it’s plugged in, Mr. Schwartz said, it’s “set it and forget it.”

“We try to make it as easy as possible for doctors to record their video – which means we don’t want them to have to do anything different about their normal clinical workflow in order to generate these videos,” Mr. Schwartz said. Physicians don’t even have to press a start or stop button – Virgo’s machine-learning algorithm detects when to start and stop video recording by discerning when the scope is inserted and removed.

“A goal of ours is to change the paradigm for endoscopy to help make sure that every procedure is captured in HD to the cloud,” he said.

The service also includes an “auto-highlight” feature that detects important moments in the procedure video. It automatically marks points in the video when the physician takes a still image and moments when an instrument, such as a snare or forceps, is present in the field of view. This, Mr. Schwartz said, makes it “easy in playback to focus on important aspects of the procedure.”

There is also a clinical trial screening feature, called “auto IBD,” that involves an algorithm that assesses videos to identify patients most likely to be eligible candidates for clinical trials. Mr. Schwartz said that procedures and patients who might go unconsidered – if they are performed at an affiliated community hospital or at an endoscopy center, for instance – can now be brought to the attention of trial investigators, without the need to comb through hundreds or thousands of candidates.

“We believe there are many more patients with these diseases that are eligible for IBD clinical trials than are currently being exposed to research opportunities within large health systems,” he said.

The proceeds from the AGA’s Opportunity Fund will be used, in part, to expand Virgo’s reach, he added. Virgo’s connection with the AGA began with its participation in the AGA Tech Summit Shark Tank competition in 2018.

“For us, the name of the game is getting Virgo in the hands of as many physicians and health systems as possible,” Mr. Schwartz said. “So we’ll be using these proceeds to build up the team and work on global distribution.” The company is also “looking to refine machine-learning algorithms and build out new features and tools.”

Gellad_Ziad_F_DUKE_web.jpg

Ziad Gellad, MD, MPH, associate professor of medicine in gastroenterology at Duke University, Durham, N.C., was one of the Opportunity Fund’s earliest member investors.

“I was looking for ways to diversify my portfolio and this was an attractive way to get into an area of investment that is not easily accessible, and so I was excited about that,” said Dr. Gellad, who himself is cofounder of a health start-up that develops software for patient navigation and outcomes collection but is not associated with the fund.

“As a start-up cofounder myself, I understand the needs of founders of companies, especially those in the GI space and appreciate the struggles they face,” Dr. Gellad added. “The opportunity to contribute to that was appealing.”

“I also believe that specialty societies like the AGA need to diversify their funding strategy and I think this is a really innovative way to do that,” he said.

The American Gastroenterological Association has made the first investment through its new venture capital fund – an initiative that gives gastroenterologists a financial opportunity combined with a chance to help corporations trying to make a difference in the field.

The fund – called the GI Opportunity Fund 1 – invests in fast-growing, early-stage companies, with the goal of hastening innovation that could ultimately help patients with digestive diseases. It was established in partnership with Varia Ventures.

The AGA recently announced the fund’s first investment with Carlsbad, Calif.–based Virgo Surgical Video Solutions, which offers endoscopy video recording that uses artificial intelligence for ease of use during procedures, for reviewing video later, and for using video to connect trial investigators with potential candidates.

Kosinski_Lawrence_2022_web.JPG

“While AGA has long guided innovators who share our goal of improving digestive health care, we have doubled down on this commitment by establishing the GI Opportunity Fund,” said Lawrence Kosinski, MD, AGAF, AGA Governing Board Councilor for Development and Growth. “The fund’s first investment – Virgo – exemplifies our pursuit of improved clinical care.”

He said the fund gives physicians a chance to work closely with AGA to invest in difference-making ventures.

“Through our venture fund, gastroenterologists can join AGA to invest in fast-growing, early-stage companies that are transforming care for patients with digestive disease,” Dr. Kosinski said.

Schwartz_Matthew_web.jpg

Virgo CEO Matthew Z. Schwartz said the company’s product is intended to fill an important need.

“We recognized that it was really difficult for doctors to capture endoscopy procedures video in high-definition at scale,” he said. “Generally, they were just taking still images. And the images were often not of great quality.”

Virgo offers a small device that connects to existing endoscopy equipment, plugging into the back of a video processor, securely compressing and encrypting video and sending it to Virgo’s HIPAA-compliant cloud storage Web portal. Once it’s plugged in, Mr. Schwartz said, it’s “set it and forget it.”

“We try to make it as easy as possible for doctors to record their video – which means we don’t want them to have to do anything different about their normal clinical workflow in order to generate these videos,” Mr. Schwartz said. Physicians don’t even have to press a start or stop button – Virgo’s machine-learning algorithm detects when to start and stop video recording by discerning when the scope is inserted and removed.

“A goal of ours is to change the paradigm for endoscopy to help make sure that every procedure is captured in HD to the cloud,” he said.

The service also includes an “auto-highlight” feature that detects important moments in the procedure video. It automatically marks points in the video when the physician takes a still image and moments when an instrument, such as a snare or forceps, is present in the field of view. This, Mr. Schwartz said, makes it “easy in playback to focus on important aspects of the procedure.”

There is also a clinical trial screening feature, called “auto IBD,” that involves an algorithm that assesses videos to identify patients most likely to be eligible candidates for clinical trials. Mr. Schwartz said that procedures and patients who might go unconsidered – if they are performed at an affiliated community hospital or at an endoscopy center, for instance – can now be brought to the attention of trial investigators, without the need to comb through hundreds or thousands of candidates.

“We believe there are many more patients with these diseases that are eligible for IBD clinical trials than are currently being exposed to research opportunities within large health systems,” he said.

The proceeds from the AGA’s Opportunity Fund will be used, in part, to expand Virgo’s reach, he added. Virgo’s connection with the AGA began with its participation in the AGA Tech Summit Shark Tank competition in 2018.

“For us, the name of the game is getting Virgo in the hands of as many physicians and health systems as possible,” Mr. Schwartz said. “So we’ll be using these proceeds to build up the team and work on global distribution.” The company is also “looking to refine machine-learning algorithms and build out new features and tools.”

Gellad_Ziad_F_DUKE_web.jpg

Ziad Gellad, MD, MPH, associate professor of medicine in gastroenterology at Duke University, Durham, N.C., was one of the Opportunity Fund’s earliest member investors.

“I was looking for ways to diversify my portfolio and this was an attractive way to get into an area of investment that is not easily accessible, and so I was excited about that,” said Dr. Gellad, who himself is cofounder of a health start-up that develops software for patient navigation and outcomes collection but is not associated with the fund.

“As a start-up cofounder myself, I understand the needs of founders of companies, especially those in the GI space and appreciate the struggles they face,” Dr. Gellad added. “The opportunity to contribute to that was appealing.”

“I also believe that specialty societies like the AGA need to diversify their funding strategy and I think this is a really innovative way to do that,” he said.

The American Gastroenterological Association has made the first investment through its new venture capital fund – an initiative that gives gastroenterologists a financial opportunity combined with a chance to help corporations trying to make a difference in the field.

The fund – called the GI Opportunity Fund 1 – invests in fast-growing, early-stage companies, with the goal of hastening innovation that could ultimately help patients with digestive diseases. It was established in partnership with Varia Ventures.

The AGA recently announced the fund’s first investment with Carlsbad, Calif.–based Virgo Surgical Video Solutions, which offers endoscopy video recording that uses artificial intelligence for ease of use during procedures, for reviewing video later, and for using video to connect trial investigators with potential candidates.

Kosinski_Lawrence_2022_web.JPG

“While AGA has long guided innovators who share our goal of improving digestive health care, we have doubled down on this commitment by establishing the GI Opportunity Fund,” said Lawrence Kosinski, MD, AGAF, AGA Governing Board Councilor for Development and Growth. “The fund’s first investment – Virgo – exemplifies our pursuit of improved clinical care.”

He said the fund gives physicians a chance to work closely with AGA to invest in difference-making ventures.

“Through our venture fund, gastroenterologists can join AGA to invest in fast-growing, early-stage companies that are transforming care for patients with digestive disease,” Dr. Kosinski said.

Schwartz_Matthew_web.jpg

Virgo CEO Matthew Z. Schwartz said the company’s product is intended to fill an important need.

“We recognized that it was really difficult for doctors to capture endoscopy procedures video in high-definition at scale,” he said. “Generally, they were just taking still images. And the images were often not of great quality.”

Virgo offers a small device that connects to existing endoscopy equipment, plugging into the back of a video processor, securely compressing and encrypting video and sending it to Virgo’s HIPAA-compliant cloud storage Web portal. Once it’s plugged in, Mr. Schwartz said, it’s “set it and forget it.”

“We try to make it as easy as possible for doctors to record their video – which means we don’t want them to have to do anything different about their normal clinical workflow in order to generate these videos,” Mr. Schwartz said. Physicians don’t even have to press a start or stop button – Virgo’s machine-learning algorithm detects when to start and stop video recording by discerning when the scope is inserted and removed.

“A goal of ours is to change the paradigm for endoscopy to help make sure that every procedure is captured in HD to the cloud,” he said.

The service also includes an “auto-highlight” feature that detects important moments in the procedure video. It automatically marks points in the video when the physician takes a still image and moments when an instrument, such as a snare or forceps, is present in the field of view. This, Mr. Schwartz said, makes it “easy in playback to focus on important aspects of the procedure.”

There is also a clinical trial screening feature, called “auto IBD,” that involves an algorithm that assesses videos to identify patients most likely to be eligible candidates for clinical trials. Mr. Schwartz said that procedures and patients who might go unconsidered – if they are performed at an affiliated community hospital or at an endoscopy center, for instance – can now be brought to the attention of trial investigators, without the need to comb through hundreds or thousands of candidates.

“We believe there are many more patients with these diseases that are eligible for IBD clinical trials than are currently being exposed to research opportunities within large health systems,” he said.

The proceeds from the AGA’s Opportunity Fund will be used, in part, to expand Virgo’s reach, he added. Virgo’s connection with the AGA began with its participation in the AGA Tech Summit Shark Tank competition in 2018.

“For us, the name of the game is getting Virgo in the hands of as many physicians and health systems as possible,” Mr. Schwartz said. “So we’ll be using these proceeds to build up the team and work on global distribution.” The company is also “looking to refine machine-learning algorithms and build out new features and tools.”

Gellad_Ziad_F_DUKE_web.jpg

Ziad Gellad, MD, MPH, associate professor of medicine in gastroenterology at Duke University, Durham, N.C., was one of the Opportunity Fund’s earliest member investors.

“I was looking for ways to diversify my portfolio and this was an attractive way to get into an area of investment that is not easily accessible, and so I was excited about that,” said Dr. Gellad, who himself is cofounder of a health start-up that develops software for patient navigation and outcomes collection but is not associated with the fund.

“As a start-up cofounder myself, I understand the needs of founders of companies, especially those in the GI space and appreciate the struggles they face,” Dr. Gellad added. “The opportunity to contribute to that was appealing.”

“I also believe that specialty societies like the AGA need to diversify their funding strategy and I think this is a really innovative way to do that,” he said.

A newly discovered strain of bacteria could play a role in the development of rheumatoid arthritis, according to findings recently published in Science Translational Medicine.

Mice colonized with a strain of Subdoligranulum bacteria in their gut – a strain previously unidentified but now named Subdoligranulum didolesgii – developed joint swelling and inflammation as well as antibodies and T-cell responses similar to what is seen in RA, researchers reported.

Kuhn_Kristine_CO_web.jpg

“This was the first time that anyone has observed arthritis developing in a mouse that was not otherwise immunologically stimulated with an adjuvant of some kind, or genetically manipulated,” said Kristine Kuhn, MD, PhD, associate professor of rheumatology at the University of Colorado at Denver, Aurora, who led a team of researchers that also included investigators from Stanford (Calif.) University and Benaroya Research Institute in Seattle.

The findings offer the latest evidence – and perhaps the most compelling evidence – for the mucosal origins hypothesis, the idea that rheumatoid arthritis can start with an immune response somewhere in the mucosa because of environmental interactions, and then becomes systemic, resulting in symptoms in the joints. Anti-citrullinated protein antibodies (ACPA), hallmarks of RA, have been found at mucosal surfaces in the periodontium and the lungs, and there have been reports of them in the intestine and cervicovaginal mucosa as well.

The latest findings that implicate the new bacterium build on previous findings in which people at risk of RA, but without symptoms yet, had an expansion of B cells producing immunoglobulin A (IgA), an antibody found in the mucosa. A closer look at these B cells, using variable region sequencing, found that they arose from a family that includes both IgA and IgG members. Because IgG antibodies are systemic, this suggested a kind of evolution from an IgA-based, mucosal immune response to one that is systemic and could target the joints.

Researchers mixed monoclonal antibodies from these B cells with a pool of bacteria from the stool of a broad population of people, and then pulled out the bacteria bound by these antibodies, and sequenced them. They found that the antibodies had bound almost exclusively to Ruminococcaceae and Lachnospiraceae.

[embed:render:related:node:246444]

They then cultured the stool of an individual at risk of developing RA and ended up with five isolates within Ruminococcaceae – “all of which belonged to the Subdoligranulum genus,” Dr. Kuhn said. When they sequenced these, they found that they had a new strain, which was named by Meagan Chriswell, an MD-PhD candidate and member of the Cherokee Nation of Oklahoma, who chose a term based on the Cherokee word for rheumatism.

Researchers at Benaroya then mixed this strain with T cells of people with RA, and those of controls, and only the T cells of those with RA were stimulated by the bacterium, they found.

“When intestines of germ-free mice were colonized with the strain, we found that they were getting arthritis,” Dr. Kuhn said. Photos of the joints show a striking contrast between the swollen joints of the mice given Subdoligranulum didolesgii and those injected with Prevotella copri, another strain suspected of having a link to RA, as well as with another Subdoligranulum strain and a sterile media. Dr. Kuhn noted that the P. copri strain did not come from an RA-affected individual.

“We thought that our results closed the loop nicely to show that these immune responses truly were toward the Subdoligranulum, and also stimulating arthritis,” she said.

The researchers then assessed the prevalence of the strain in people at risk for RA or with RA, and in controls. They found it in 17% of those with or at risk for RA but didn’t see it at all in the healthy control population.

Dr. Kuhn and her research team, she said, are now looking at the prevalence of the strain in a larger population and doing more investigating into the link with RA.

“Does it really associate with the development of immune responses and the development of rheumatoid arthritis?” she said.

Potential etiologic role of P. copri

Another paper, published in Arthritis & Rheumatology by some of the same investigators a week before the study describing the Subdoligranulum findings, tried to ascertain the point at which individuals might develop antibodies to P. copri, which for about a decade has been suspected of having a link to the development of RA.

They found that those with early RA had higher median values of IgG anti–P. copri (Pc) antibodies, compared with matched controls. People with established RA also had higher values of IgA anti-Pc antibodies. Those with ACPA, but not rheumatoid factor (RF), showed a trend toward higher IgG anti-Pc antibodies. Those who were ACPA-positive and RF-positive had significantly increased levels of IgA anti-Pc antibodies and a trend toward higher levels of IgG anti-Pc antibodies, compared with matched controls.

The findings, according to the researchers, “support a potential etiologic role for this microorganism in both RA preclinical evolution and the subsequent pathogenesis of synovitis.”

Dr. Kuhn and others in the field say it’s likely that many microbes play a role in the development of RA, and that the P. copri findings only add evidence of that relationship.

“Maybe the bacteria are involved at different parts of the pathway, and maybe they’re involved in triggering different parts of the immune responses,” she said. “Those are all to be determined.”

Dan Littman, MD, PhD, professor of rheumatology at New York University, who wrote a commentary reflecting on the findings of the Subdoligranulum study, said the results are “another piece of data” adding to the evidence base for the mucosal origins hypothesis.

[embed:render:related:node:233837]

“It’s by no means proven that this is the way pathogenesis in RA can occur, but it’s certainly a very solid study,” said Dr. Littman, who with colleagues published findings in 2013 linking P. copri to RA. “What makes it most compelling is that they seem to be able to show some evidence of causality in the mouse model.”

Littman_Dan_NY_web.jpg

A newly discovered strain of bacteria could play a role in the development of rheumatoid arthritis, according to findings recently published in Science Translational Medicine.

Mice colonized with a strain of Subdoligranulum bacteria in their gut – a strain previously unidentified but now named Subdoligranulum didolesgii – developed joint swelling and inflammation as well as antibodies and T-cell responses similar to what is seen in RA, researchers reported.

Kuhn_Kristine_CO_web.jpg

“This was the first time that anyone has observed arthritis developing in a mouse that was not otherwise immunologically stimulated with an adjuvant of some kind, or genetically manipulated,” said Kristine Kuhn, MD, PhD, associate professor of rheumatology at the University of Colorado at Denver, Aurora, who led a team of researchers that also included investigators from Stanford (Calif.) University and Benaroya Research Institute in Seattle.

The findings offer the latest evidence – and perhaps the most compelling evidence – for the mucosal origins hypothesis, the idea that rheumatoid arthritis can start with an immune response somewhere in the mucosa because of environmental interactions, and then becomes systemic, resulting in symptoms in the joints. Anti-citrullinated protein antibodies (ACPA), hallmarks of RA, have been found at mucosal surfaces in the periodontium and the lungs, and there have been reports of them in the intestine and cervicovaginal mucosa as well.

The latest findings that implicate the new bacterium build on previous findings in which people at risk of RA, but without symptoms yet, had an expansion of B cells producing immunoglobulin A (IgA), an antibody found in the mucosa. A closer look at these B cells, using variable region sequencing, found that they arose from a family that includes both IgA and IgG members. Because IgG antibodies are systemic, this suggested a kind of evolution from an IgA-based, mucosal immune response to one that is systemic and could target the joints.

Researchers mixed monoclonal antibodies from these B cells with a pool of bacteria from the stool of a broad population of people, and then pulled out the bacteria bound by these antibodies, and sequenced them. They found that the antibodies had bound almost exclusively to Ruminococcaceae and Lachnospiraceae.

[embed:render:related:node:246444]

They then cultured the stool of an individual at risk of developing RA and ended up with five isolates within Ruminococcaceae – “all of which belonged to the Subdoligranulum genus,” Dr. Kuhn said. When they sequenced these, they found that they had a new strain, which was named by Meagan Chriswell, an MD-PhD candidate and member of the Cherokee Nation of Oklahoma, who chose a term based on the Cherokee word for rheumatism.

Researchers at Benaroya then mixed this strain with T cells of people with RA, and those of controls, and only the T cells of those with RA were stimulated by the bacterium, they found.

“When intestines of germ-free mice were colonized with the strain, we found that they were getting arthritis,” Dr. Kuhn said. Photos of the joints show a striking contrast between the swollen joints of the mice given Subdoligranulum didolesgii and those injected with Prevotella copri, another strain suspected of having a link to RA, as well as with another Subdoligranulum strain and a sterile media. Dr. Kuhn noted that the P. copri strain did not come from an RA-affected individual.

“We thought that our results closed the loop nicely to show that these immune responses truly were toward the Subdoligranulum, and also stimulating arthritis,” she said.

The researchers then assessed the prevalence of the strain in people at risk for RA or with RA, and in controls. They found it in 17% of those with or at risk for RA but didn’t see it at all in the healthy control population.

Dr. Kuhn and her research team, she said, are now looking at the prevalence of the strain in a larger population and doing more investigating into the link with RA.

“Does it really associate with the development of immune responses and the development of rheumatoid arthritis?” she said.

Potential etiologic role of P. copri

Another paper, published in Arthritis & Rheumatology by some of the same investigators a week before the study describing the Subdoligranulum findings, tried to ascertain the point at which individuals might develop antibodies to P. copri, which for about a decade has been suspected of having a link to the development of RA.

They found that those with early RA had higher median values of IgG anti–P. copri (Pc) antibodies, compared with matched controls. People with established RA also had higher values of IgA anti-Pc antibodies. Those with ACPA, but not rheumatoid factor (RF), showed a trend toward higher IgG anti-Pc antibodies. Those who were ACPA-positive and RF-positive had significantly increased levels of IgA anti-Pc antibodies and a trend toward higher levels of IgG anti-Pc antibodies, compared with matched controls.

The findings, according to the researchers, “support a potential etiologic role for this microorganism in both RA preclinical evolution and the subsequent pathogenesis of synovitis.”

Dr. Kuhn and others in the field say it’s likely that many microbes play a role in the development of RA, and that the P. copri findings only add evidence of that relationship.

“Maybe the bacteria are involved at different parts of the pathway, and maybe they’re involved in triggering different parts of the immune responses,” she said. “Those are all to be determined.”

Dan Littman, MD, PhD, professor of rheumatology at New York University, who wrote a commentary reflecting on the findings of the Subdoligranulum study, said the results are “another piece of data” adding to the evidence base for the mucosal origins hypothesis.

[embed:render:related:node:233837]

“It’s by no means proven that this is the way pathogenesis in RA can occur, but it’s certainly a very solid study,” said Dr. Littman, who with colleagues published findings in 2013 linking P. copri to RA. “What makes it most compelling is that they seem to be able to show some evidence of causality in the mouse model.”

Littman_Dan_NY_web.jpg

A newly discovered strain of bacteria could play a role in the development of rheumatoid arthritis, according to findings recently published in Science Translational Medicine.

Mice colonized with a strain of Subdoligranulum bacteria in their gut – a strain previously unidentified but now named Subdoligranulum didolesgii – developed joint swelling and inflammation as well as antibodies and T-cell responses similar to what is seen in RA, researchers reported.

Kuhn_Kristine_CO_web.jpg

“This was the first time that anyone has observed arthritis developing in a mouse that was not otherwise immunologically stimulated with an adjuvant of some kind, or genetically manipulated,” said Kristine Kuhn, MD, PhD, associate professor of rheumatology at the University of Colorado at Denver, Aurora, who led a team of researchers that also included investigators from Stanford (Calif.) University and Benaroya Research Institute in Seattle.

The findings offer the latest evidence – and perhaps the most compelling evidence – for the mucosal origins hypothesis, the idea that rheumatoid arthritis can start with an immune response somewhere in the mucosa because of environmental interactions, and then becomes systemic, resulting in symptoms in the joints. Anti-citrullinated protein antibodies (ACPA), hallmarks of RA, have been found at mucosal surfaces in the periodontium and the lungs, and there have been reports of them in the intestine and cervicovaginal mucosa as well.

The latest findings that implicate the new bacterium build on previous findings in which people at risk of RA, but without symptoms yet, had an expansion of B cells producing immunoglobulin A (IgA), an antibody found in the mucosa. A closer look at these B cells, using variable region sequencing, found that they arose from a family that includes both IgA and IgG members. Because IgG antibodies are systemic, this suggested a kind of evolution from an IgA-based, mucosal immune response to one that is systemic and could target the joints.

Researchers mixed monoclonal antibodies from these B cells with a pool of bacteria from the stool of a broad population of people, and then pulled out the bacteria bound by these antibodies, and sequenced them. They found that the antibodies had bound almost exclusively to Ruminococcaceae and Lachnospiraceae.

[embed:render:related:node:246444]

They then cultured the stool of an individual at risk of developing RA and ended up with five isolates within Ruminococcaceae – “all of which belonged to the Subdoligranulum genus,” Dr. Kuhn said. When they sequenced these, they found that they had a new strain, which was named by Meagan Chriswell, an MD-PhD candidate and member of the Cherokee Nation of Oklahoma, who chose a term based on the Cherokee word for rheumatism.

Researchers at Benaroya then mixed this strain with T cells of people with RA, and those of controls, and only the T cells of those with RA were stimulated by the bacterium, they found.

“When intestines of germ-free mice were colonized with the strain, we found that they were getting arthritis,” Dr. Kuhn said. Photos of the joints show a striking contrast between the swollen joints of the mice given Subdoligranulum didolesgii and those injected with Prevotella copri, another strain suspected of having a link to RA, as well as with another Subdoligranulum strain and a sterile media. Dr. Kuhn noted that the P. copri strain did not come from an RA-affected individual.

“We thought that our results closed the loop nicely to show that these immune responses truly were toward the Subdoligranulum, and also stimulating arthritis,” she said.

The researchers then assessed the prevalence of the strain in people at risk for RA or with RA, and in controls. They found it in 17% of those with or at risk for RA but didn’t see it at all in the healthy control population.

Dr. Kuhn and her research team, she said, are now looking at the prevalence of the strain in a larger population and doing more investigating into the link with RA.

“Does it really associate with the development of immune responses and the development of rheumatoid arthritis?” she said.

Potential etiologic role of P. copri

Another paper, published in Arthritis & Rheumatology by some of the same investigators a week before the study describing the Subdoligranulum findings, tried to ascertain the point at which individuals might develop antibodies to P. copri, which for about a decade has been suspected of having a link to the development of RA.

They found that those with early RA had higher median values of IgG anti–P. copri (Pc) antibodies, compared with matched controls. People with established RA also had higher values of IgA anti-Pc antibodies. Those with ACPA, but not rheumatoid factor (RF), showed a trend toward higher IgG anti-Pc antibodies. Those who were ACPA-positive and RF-positive had significantly increased levels of IgA anti-Pc antibodies and a trend toward higher levels of IgG anti-Pc antibodies, compared with matched controls.

The findings, according to the researchers, “support a potential etiologic role for this microorganism in both RA preclinical evolution and the subsequent pathogenesis of synovitis.”

Dr. Kuhn and others in the field say it’s likely that many microbes play a role in the development of RA, and that the P. copri findings only add evidence of that relationship.

“Maybe the bacteria are involved at different parts of the pathway, and maybe they’re involved in triggering different parts of the immune responses,” she said. “Those are all to be determined.”

Dan Littman, MD, PhD, professor of rheumatology at New York University, who wrote a commentary reflecting on the findings of the Subdoligranulum study, said the results are “another piece of data” adding to the evidence base for the mucosal origins hypothesis.

[embed:render:related:node:233837]

“It’s by no means proven that this is the way pathogenesis in RA can occur, but it’s certainly a very solid study,” said Dr. Littman, who with colleagues published findings in 2013 linking P. copri to RA. “What makes it most compelling is that they seem to be able to show some evidence of causality in the mouse model.”

Littman_Dan_NY_web.jpg

Visits to the emergency department for asthma increase more than a year before a failed inspection by the U.S. Department of Housing and Urban Development (HUD), according to a new study presented at the annual meeting of the American College of Emergency Physicians.

While links between asthma and low-quality housing prone to harboring allergens have been well-documented, the current study takes the extra step of looking at housing down to the level of individual land parcels and suggests that asthma hospital visits can be used to identify hazardous housing earlier.

“Emergency department visits for asthma provide a leading indicator that can be used by health departments or housing authorities to direct housing inspections and remediation of poor housing conditions, track improvements in housing quality, measure housing department performance, support resident grievances, and inform funding allocation decisions,” said the study’s lead researcher, Elizabeth Samuels, MD, who is assistant professor of epidemiology and emergency medicine at Brown University, Providence, R.I.

Researchers retrospectively looked at cases of children and adults in the Greater New Haven area of Connecticut seen at the Yale New Haven Hospital ED for asthma-related problems between March 2013 and August 2017. The region has the fifth-highest prevalence of asthma in the United States, the researchers point out, due to its air quality, pollens, and quality of its housing. More than half of residences were built before 1,940, compared with about 13% nationally. Patient addresses were matched with HUD inspection records.

The review encompassed 11,429 ED visits by 6,366 individuals; 54% were insured by Medicaid, and 42% were Black. Controlling for patient and neighborhood data, researchers found that increased asthma ED visits at the parcel level were associated with decreased HUD inspection scores to a highly significant degree (P < .001).

They also found that there was a relationship in terms of timing between asthma ED visits and inspection scores: asthma ED visits increased more than 1 year before a failed HUD inspection. They also found that asthma ED visits were not elevated at housing units that passed inspection. Using asthma ED visits to predict failed housing inspections produced a specificity rate of 92.3% in an adjusted model, Dr. Samuels noted.

“This approach represents a novel method of early identification of dangerous housing conditions, which could aid in the prevention of asthma-related morbidity and mortality,” Dr. Samuels said.

The investigators noted that, of the parcels with the top three incidence rates of asthma ED visits, “all of them have been closed or demolished.”

In addition to limiting exposure of patients with asthma to the allergens of mold, mice and rats, and cockroaches, improving poor-quality housing earlier could help asthma by reducing stress, she said.

“There is also an increasing evidence base that psychosocial stress increases the risk of asthma attacks, and it’s therefore possible that living in poor housing conditions – often highly stressful situations – drives exacerbation risk via this pathway,” she said. “Synergistic effects between these pathways are also possible or even likely.”

Neeta Thakur, MD, associate professor of medicine at the University of California, San Francisco, who researches asthma, said the findings could lead to a strategy for improving poor-quality housing more quickly. As it is, inspections are too infrequent, often prompted by resident complaints.

“Once the complaints get to a certain threshold, then there might be an inspection that happens, and if there is a periodic review of the buildings, they often happen few and far between,” she said. “We could actually use some of the information that we’re already getting from something like ED visits and see if there is a pattern.”

An important follow-up would be to see whether asthma outcomes improve after housing deficiencies are addressed and whether the predictive capacity of ED visits occurs in other places.

“Would you then see a decline in the ED visit rates from individuals living in those buildings?” Dr. Thakur said. “It’s important to find a leading indicator, but you want to be sure that that leading indicator is useful as something that can be intervened upon.”

Dr. Samuels and Dr. Thakur have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Visits to the emergency department for asthma increase more than a year before a failed inspection by the U.S. Department of Housing and Urban Development (HUD), according to a new study presented at the annual meeting of the American College of Emergency Physicians.

While links between asthma and low-quality housing prone to harboring allergens have been well-documented, the current study takes the extra step of looking at housing down to the level of individual land parcels and suggests that asthma hospital visits can be used to identify hazardous housing earlier.

“Emergency department visits for asthma provide a leading indicator that can be used by health departments or housing authorities to direct housing inspections and remediation of poor housing conditions, track improvements in housing quality, measure housing department performance, support resident grievances, and inform funding allocation decisions,” said the study’s lead researcher, Elizabeth Samuels, MD, who is assistant professor of epidemiology and emergency medicine at Brown University, Providence, R.I.

Researchers retrospectively looked at cases of children and adults in the Greater New Haven area of Connecticut seen at the Yale New Haven Hospital ED for asthma-related problems between March 2013 and August 2017. The region has the fifth-highest prevalence of asthma in the United States, the researchers point out, due to its air quality, pollens, and quality of its housing. More than half of residences were built before 1,940, compared with about 13% nationally. Patient addresses were matched with HUD inspection records.

The review encompassed 11,429 ED visits by 6,366 individuals; 54% were insured by Medicaid, and 42% were Black. Controlling for patient and neighborhood data, researchers found that increased asthma ED visits at the parcel level were associated with decreased HUD inspection scores to a highly significant degree (P < .001).

They also found that there was a relationship in terms of timing between asthma ED visits and inspection scores: asthma ED visits increased more than 1 year before a failed HUD inspection. They also found that asthma ED visits were not elevated at housing units that passed inspection. Using asthma ED visits to predict failed housing inspections produced a specificity rate of 92.3% in an adjusted model, Dr. Samuels noted.

“This approach represents a novel method of early identification of dangerous housing conditions, which could aid in the prevention of asthma-related morbidity and mortality,” Dr. Samuels said.

The investigators noted that, of the parcels with the top three incidence rates of asthma ED visits, “all of them have been closed or demolished.”

In addition to limiting exposure of patients with asthma to the allergens of mold, mice and rats, and cockroaches, improving poor-quality housing earlier could help asthma by reducing stress, she said.

“There is also an increasing evidence base that psychosocial stress increases the risk of asthma attacks, and it’s therefore possible that living in poor housing conditions – often highly stressful situations – drives exacerbation risk via this pathway,” she said. “Synergistic effects between these pathways are also possible or even likely.”

Neeta Thakur, MD, associate professor of medicine at the University of California, San Francisco, who researches asthma, said the findings could lead to a strategy for improving poor-quality housing more quickly. As it is, inspections are too infrequent, often prompted by resident complaints.

“Once the complaints get to a certain threshold, then there might be an inspection that happens, and if there is a periodic review of the buildings, they often happen few and far between,” she said. “We could actually use some of the information that we’re already getting from something like ED visits and see if there is a pattern.”

An important follow-up would be to see whether asthma outcomes improve after housing deficiencies are addressed and whether the predictive capacity of ED visits occurs in other places.

“Would you then see a decline in the ED visit rates from individuals living in those buildings?” Dr. Thakur said. “It’s important to find a leading indicator, but you want to be sure that that leading indicator is useful as something that can be intervened upon.”

Dr. Samuels and Dr. Thakur have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Visits to the emergency department for asthma increase more than a year before a failed inspection by the U.S. Department of Housing and Urban Development (HUD), according to a new study presented at the annual meeting of the American College of Emergency Physicians.

While links between asthma and low-quality housing prone to harboring allergens have been well-documented, the current study takes the extra step of looking at housing down to the level of individual land parcels and suggests that asthma hospital visits can be used to identify hazardous housing earlier.

“Emergency department visits for asthma provide a leading indicator that can be used by health departments or housing authorities to direct housing inspections and remediation of poor housing conditions, track improvements in housing quality, measure housing department performance, support resident grievances, and inform funding allocation decisions,” said the study’s lead researcher, Elizabeth Samuels, MD, who is assistant professor of epidemiology and emergency medicine at Brown University, Providence, R.I.

Researchers retrospectively looked at cases of children and adults in the Greater New Haven area of Connecticut seen at the Yale New Haven Hospital ED for asthma-related problems between March 2013 and August 2017. The region has the fifth-highest prevalence of asthma in the United States, the researchers point out, due to its air quality, pollens, and quality of its housing. More than half of residences were built before 1,940, compared with about 13% nationally. Patient addresses were matched with HUD inspection records.

The review encompassed 11,429 ED visits by 6,366 individuals; 54% were insured by Medicaid, and 42% were Black. Controlling for patient and neighborhood data, researchers found that increased asthma ED visits at the parcel level were associated with decreased HUD inspection scores to a highly significant degree (P < .001).

They also found that there was a relationship in terms of timing between asthma ED visits and inspection scores: asthma ED visits increased more than 1 year before a failed HUD inspection. They also found that asthma ED visits were not elevated at housing units that passed inspection. Using asthma ED visits to predict failed housing inspections produced a specificity rate of 92.3% in an adjusted model, Dr. Samuels noted.

“This approach represents a novel method of early identification of dangerous housing conditions, which could aid in the prevention of asthma-related morbidity and mortality,” Dr. Samuels said.

The investigators noted that, of the parcels with the top three incidence rates of asthma ED visits, “all of them have been closed or demolished.”

In addition to limiting exposure of patients with asthma to the allergens of mold, mice and rats, and cockroaches, improving poor-quality housing earlier could help asthma by reducing stress, she said.

“There is also an increasing evidence base that psychosocial stress increases the risk of asthma attacks, and it’s therefore possible that living in poor housing conditions – often highly stressful situations – drives exacerbation risk via this pathway,” she said. “Synergistic effects between these pathways are also possible or even likely.”

Neeta Thakur, MD, associate professor of medicine at the University of California, San Francisco, who researches asthma, said the findings could lead to a strategy for improving poor-quality housing more quickly. As it is, inspections are too infrequent, often prompted by resident complaints.

“Once the complaints get to a certain threshold, then there might be an inspection that happens, and if there is a periodic review of the buildings, they often happen few and far between,” she said. “We could actually use some of the information that we’re already getting from something like ED visits and see if there is a pattern.”

An important follow-up would be to see whether asthma outcomes improve after housing deficiencies are addressed and whether the predictive capacity of ED visits occurs in other places.

“Would you then see a decline in the ED visit rates from individuals living in those buildings?” Dr. Thakur said. “It’s important to find a leading indicator, but you want to be sure that that leading indicator is useful as something that can be intervened upon.”

Dr. Samuels and Dr. Thakur have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new analysis shows that pulse oximetry is not reliable enough to be used to diagnose carbon monoxide poisoning, researchers said at the annual European Emergency Medicine Congress.

A review of the literature found that the approach, while simple and easy to do, does not identify carbon monoxide poisoning almost a quarter of the time.

“This method is not accurate enough and should not be used in clinical practice,” said Mathilde Papin, MD, a researcher in the emergency department at Nantes (France) University.

Carbon monoxide poisoning is one of the world’s most common causes of poisoning deaths. When people are exposed to the colorless, odorless carbon monoxide, it enters their bloodstream and attaches to hemoglobin, a transporter of oxygen, thereby starving the body of oxygen. It can be treated with oxygen, but the problem is that its symptoms can be similar to infections, such as the flu, and can be difficult to diagnose.

A blood test is available, measuring the amount of hemoglobin that’s attached to carbon dioxide. But, the researchers said, a test is needed that can be done quickly right in the ambulance or emergency room.

“A blood test is reliable, but not practical,” Dr. Papin said.

One quick and simple method is pulse oximetry, in which a device is placed on the finger. A lower level of oxygen saturation could be a sign of oxygen displacement from carbon monoxide poisoning. However, the approach has delivered mixed results.

Researchers led a systematic review and meta-analysis and searched for all trials that compared pulse oximetry with blood tests. They found 19 and were able to combine the results of 11 of them, which amounted to data on more than 2,000 people, some with carbon monoxide poisoning and some healthy.

Pulse oximetry had a sensitivity of 77% and a specificity of 83%, with an overall accuracy of 86%. Dr. Papin said this is not good enough, pointing to the relatively low sensitivity.

“At 23%, the false negative rate with pulse oximetry is too high for reliably triaging patients with suspected carbon monoxide poisoning,” she said. 

Dr. Papin noted that the findings were not all that surprising, given the experience at her own center.

“The idea of this meta-analysis came from the clinical impression that this device was not as accurate as it should be in everyday use in our ED,” she said. Pulse oximetry is also routinely used in prehospital care, she said, adding to the importance of finding an alternative approach. Dr. Papin and her team are now planning to evaluate a method of faster screening of carbon monoxide levels in the capillaries.

James Chenoweth, MD, of the department of emergency medicine at the University of California, Davis, who has researched carbon monoxide treatment, said the findings show how the clinical value of pulse oximetry is limited in this context.

“In the right clinical setting” – such as smoking inhalation – “a low oxygen saturation on pulse oximetry may suggest the need for definitive testing for CO poisoning, but it can’t be used to definitively rule in or out the presence of carboxyhemoglobin,” he said. “I wouldn’t say that it should not be used, but clinicians should be aware of the potential pitfall of being falsely reassured if the pulse oximetry is normal.”

This study did not receive any specific funding. Dr. Papin and Dr. Chenoweth have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new analysis shows that pulse oximetry is not reliable enough to be used to diagnose carbon monoxide poisoning, researchers said at the annual European Emergency Medicine Congress.

A review of the literature found that the approach, while simple and easy to do, does not identify carbon monoxide poisoning almost a quarter of the time.

“This method is not accurate enough and should not be used in clinical practice,” said Mathilde Papin, MD, a researcher in the emergency department at Nantes (France) University.

Carbon monoxide poisoning is one of the world’s most common causes of poisoning deaths. When people are exposed to the colorless, odorless carbon monoxide, it enters their bloodstream and attaches to hemoglobin, a transporter of oxygen, thereby starving the body of oxygen. It can be treated with oxygen, but the problem is that its symptoms can be similar to infections, such as the flu, and can be difficult to diagnose.

A blood test is available, measuring the amount of hemoglobin that’s attached to carbon dioxide. But, the researchers said, a test is needed that can be done quickly right in the ambulance or emergency room.

“A blood test is reliable, but not practical,” Dr. Papin said.

One quick and simple method is pulse oximetry, in which a device is placed on the finger. A lower level of oxygen saturation could be a sign of oxygen displacement from carbon monoxide poisoning. However, the approach has delivered mixed results.

Researchers led a systematic review and meta-analysis and searched for all trials that compared pulse oximetry with blood tests. They found 19 and were able to combine the results of 11 of them, which amounted to data on more than 2,000 people, some with carbon monoxide poisoning and some healthy.

Pulse oximetry had a sensitivity of 77% and a specificity of 83%, with an overall accuracy of 86%. Dr. Papin said this is not good enough, pointing to the relatively low sensitivity.

“At 23%, the false negative rate with pulse oximetry is too high for reliably triaging patients with suspected carbon monoxide poisoning,” she said. 

Dr. Papin noted that the findings were not all that surprising, given the experience at her own center.

“The idea of this meta-analysis came from the clinical impression that this device was not as accurate as it should be in everyday use in our ED,” she said. Pulse oximetry is also routinely used in prehospital care, she said, adding to the importance of finding an alternative approach. Dr. Papin and her team are now planning to evaluate a method of faster screening of carbon monoxide levels in the capillaries.

James Chenoweth, MD, of the department of emergency medicine at the University of California, Davis, who has researched carbon monoxide treatment, said the findings show how the clinical value of pulse oximetry is limited in this context.

“In the right clinical setting” – such as smoking inhalation – “a low oxygen saturation on pulse oximetry may suggest the need for definitive testing for CO poisoning, but it can’t be used to definitively rule in or out the presence of carboxyhemoglobin,” he said. “I wouldn’t say that it should not be used, but clinicians should be aware of the potential pitfall of being falsely reassured if the pulse oximetry is normal.”

This study did not receive any specific funding. Dr. Papin and Dr. Chenoweth have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new analysis shows that pulse oximetry is not reliable enough to be used to diagnose carbon monoxide poisoning, researchers said at the annual European Emergency Medicine Congress.

A review of the literature found that the approach, while simple and easy to do, does not identify carbon monoxide poisoning almost a quarter of the time.

“This method is not accurate enough and should not be used in clinical practice,” said Mathilde Papin, MD, a researcher in the emergency department at Nantes (France) University.

Carbon monoxide poisoning is one of the world’s most common causes of poisoning deaths. When people are exposed to the colorless, odorless carbon monoxide, it enters their bloodstream and attaches to hemoglobin, a transporter of oxygen, thereby starving the body of oxygen. It can be treated with oxygen, but the problem is that its symptoms can be similar to infections, such as the flu, and can be difficult to diagnose.

A blood test is available, measuring the amount of hemoglobin that’s attached to carbon dioxide. But, the researchers said, a test is needed that can be done quickly right in the ambulance or emergency room.

“A blood test is reliable, but not practical,” Dr. Papin said.

One quick and simple method is pulse oximetry, in which a device is placed on the finger. A lower level of oxygen saturation could be a sign of oxygen displacement from carbon monoxide poisoning. However, the approach has delivered mixed results.

Researchers led a systematic review and meta-analysis and searched for all trials that compared pulse oximetry with blood tests. They found 19 and were able to combine the results of 11 of them, which amounted to data on more than 2,000 people, some with carbon monoxide poisoning and some healthy.

Pulse oximetry had a sensitivity of 77% and a specificity of 83%, with an overall accuracy of 86%. Dr. Papin said this is not good enough, pointing to the relatively low sensitivity.

“At 23%, the false negative rate with pulse oximetry is too high for reliably triaging patients with suspected carbon monoxide poisoning,” she said. 

Dr. Papin noted that the findings were not all that surprising, given the experience at her own center.

“The idea of this meta-analysis came from the clinical impression that this device was not as accurate as it should be in everyday use in our ED,” she said. Pulse oximetry is also routinely used in prehospital care, she said, adding to the importance of finding an alternative approach. Dr. Papin and her team are now planning to evaluate a method of faster screening of carbon monoxide levels in the capillaries.

James Chenoweth, MD, of the department of emergency medicine at the University of California, Davis, who has researched carbon monoxide treatment, said the findings show how the clinical value of pulse oximetry is limited in this context.

“In the right clinical setting” – such as smoking inhalation – “a low oxygen saturation on pulse oximetry may suggest the need for definitive testing for CO poisoning, but it can’t be used to definitively rule in or out the presence of carboxyhemoglobin,” he said. “I wouldn’t say that it should not be used, but clinicians should be aware of the potential pitfall of being falsely reassured if the pulse oximetry is normal.”

This study did not receive any specific funding. Dr. Papin and Dr. Chenoweth have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Starting treatment for alcohol use disorder (AUD) with extended-release naltrexone injections in the emergency department produced a dramatic reduction in alcohol consumption, according to findings presented at the annual meeting of the American College of Emergency Physicians.

The results show the feasibility of such a program and underscore the importance of the ED in combating AUD, said the researchers, from the University of California, San Francisco.

“According to the National Institute on Alcohol Abuse and Alcoholism, 18% of ED visits had alcohol as a contributing factor – the volume of alcohol-related ED visits has been climbing every year, and it is a significant public health problem,” said Maria Raven, MD, MPH, professor of emergency medicine at UCSF. “Right now, we do very little for people who come to the ED with AUD, so it is a missed opportunity to intervene, especially given the volume of visits we see and that our patient population is one that often has significant barriers to accessing outpatient treatment.”

The findings come from a 12-week, prospective, single-arm study of ED patients who were actively drinking adults with known or suspected AUD and who had positive scores on a screening test. Of 179 patients who were approached, 32 agreed to enroll; the enrollment yield was 18%. Participants were given monthly extended-release naltrexone and case management services.

Of the 32 participants, 25 completed all their study visits and 22 (69%) continued taking naltrexone after the 12 weeks.

The researchers said the results surprised them. The average daily alcohol consumption at baseline was 7.6 drinks a day, and it fell by 7.5 drinks a day – in other words, to almost no consumption.

“The median alcohol consumption when measured over the last 2 weeks of the study was zero,” Dr. Raven said. “This doesn’t mean everyone was at zero, but this was the median and reflects that many participants stopped drinking altogether. We were pleasantly surprised by this. I don’t know that we thought so many people who participated would actually fully abstain.”

On the Kemp Quality of Life Scale – with scores from 1 to 7, with 1 being “life is very distressing,” 4 being “life is so-so,” and 7 being “life is great” – the average baseline score was 3.6. That score rose by 1.2 points by the study’s end.

Dr. Raven said she hoped more would enroll but that “a number of people actually did not want the injection or were not ready to think about stopping.” Still, the 18% enrollment is “a major improvement,” considering that no attempt was made to initiate treatment with naltrexone prior to the study. Oral naltrexone, rather than the injection, could be offered to improve participation, but oral naltrexone has to be taken daily.

She said a larger study is planned at UCSF and that other institutions are interested in starting a similar program.

“When someone is in the ED for an AUD-related issue, it can serve as a turning point for them in some cases,” she said.

Erik S. Anderson, MD, associate research director at Oakland, Calif.–based Alameda Health System, who has studied naltrexone in the ED, said the findings dovetail with what his team has found at his center. He added that psychosocial support is important as well and that his team has found that navigation services are the most important factor in connecting patients with follow-up care – even more so than providing medications.

“In my mind, this is a situation where we have treatment options and approaches that work, and it’s really about implementing these services in a novel care setting,” he said. “ED patients are at higher risk of complications for AUD simply because they are in the ED in the first place – initiating AUD treatment in this setting is the right thing to do.”

Dr. Raven and Dr. Anderson disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Starting treatment for alcohol use disorder (AUD) with extended-release naltrexone injections in the emergency department produced a dramatic reduction in alcohol consumption, according to findings presented at the annual meeting of the American College of Emergency Physicians.

The results show the feasibility of such a program and underscore the importance of the ED in combating AUD, said the researchers, from the University of California, San Francisco.

“According to the National Institute on Alcohol Abuse and Alcoholism, 18% of ED visits had alcohol as a contributing factor – the volume of alcohol-related ED visits has been climbing every year, and it is a significant public health problem,” said Maria Raven, MD, MPH, professor of emergency medicine at UCSF. “Right now, we do very little for people who come to the ED with AUD, so it is a missed opportunity to intervene, especially given the volume of visits we see and that our patient population is one that often has significant barriers to accessing outpatient treatment.”

The findings come from a 12-week, prospective, single-arm study of ED patients who were actively drinking adults with known or suspected AUD and who had positive scores on a screening test. Of 179 patients who were approached, 32 agreed to enroll; the enrollment yield was 18%. Participants were given monthly extended-release naltrexone and case management services.

Of the 32 participants, 25 completed all their study visits and 22 (69%) continued taking naltrexone after the 12 weeks.

The researchers said the results surprised them. The average daily alcohol consumption at baseline was 7.6 drinks a day, and it fell by 7.5 drinks a day – in other words, to almost no consumption.

“The median alcohol consumption when measured over the last 2 weeks of the study was zero,” Dr. Raven said. “This doesn’t mean everyone was at zero, but this was the median and reflects that many participants stopped drinking altogether. We were pleasantly surprised by this. I don’t know that we thought so many people who participated would actually fully abstain.”

On the Kemp Quality of Life Scale – with scores from 1 to 7, with 1 being “life is very distressing,” 4 being “life is so-so,” and 7 being “life is great” – the average baseline score was 3.6. That score rose by 1.2 points by the study’s end.

Dr. Raven said she hoped more would enroll but that “a number of people actually did not want the injection or were not ready to think about stopping.” Still, the 18% enrollment is “a major improvement,” considering that no attempt was made to initiate treatment with naltrexone prior to the study. Oral naltrexone, rather than the injection, could be offered to improve participation, but oral naltrexone has to be taken daily.

She said a larger study is planned at UCSF and that other institutions are interested in starting a similar program.

“When someone is in the ED for an AUD-related issue, it can serve as a turning point for them in some cases,” she said.

Erik S. Anderson, MD, associate research director at Oakland, Calif.–based Alameda Health System, who has studied naltrexone in the ED, said the findings dovetail with what his team has found at his center. He added that psychosocial support is important as well and that his team has found that navigation services are the most important factor in connecting patients with follow-up care – even more so than providing medications.

“In my mind, this is a situation where we have treatment options and approaches that work, and it’s really about implementing these services in a novel care setting,” he said. “ED patients are at higher risk of complications for AUD simply because they are in the ED in the first place – initiating AUD treatment in this setting is the right thing to do.”

Dr. Raven and Dr. Anderson disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Starting treatment for alcohol use disorder (AUD) with extended-release naltrexone injections in the emergency department produced a dramatic reduction in alcohol consumption, according to findings presented at the annual meeting of the American College of Emergency Physicians.

The results show the feasibility of such a program and underscore the importance of the ED in combating AUD, said the researchers, from the University of California, San Francisco.

“According to the National Institute on Alcohol Abuse and Alcoholism, 18% of ED visits had alcohol as a contributing factor – the volume of alcohol-related ED visits has been climbing every year, and it is a significant public health problem,” said Maria Raven, MD, MPH, professor of emergency medicine at UCSF. “Right now, we do very little for people who come to the ED with AUD, so it is a missed opportunity to intervene, especially given the volume of visits we see and that our patient population is one that often has significant barriers to accessing outpatient treatment.”

The findings come from a 12-week, prospective, single-arm study of ED patients who were actively drinking adults with known or suspected AUD and who had positive scores on a screening test. Of 179 patients who were approached, 32 agreed to enroll; the enrollment yield was 18%. Participants were given monthly extended-release naltrexone and case management services.

Of the 32 participants, 25 completed all their study visits and 22 (69%) continued taking naltrexone after the 12 weeks.

The researchers said the results surprised them. The average daily alcohol consumption at baseline was 7.6 drinks a day, and it fell by 7.5 drinks a day – in other words, to almost no consumption.

“The median alcohol consumption when measured over the last 2 weeks of the study was zero,” Dr. Raven said. “This doesn’t mean everyone was at zero, but this was the median and reflects that many participants stopped drinking altogether. We were pleasantly surprised by this. I don’t know that we thought so many people who participated would actually fully abstain.”

On the Kemp Quality of Life Scale – with scores from 1 to 7, with 1 being “life is very distressing,” 4 being “life is so-so,” and 7 being “life is great” – the average baseline score was 3.6. That score rose by 1.2 points by the study’s end.

Dr. Raven said she hoped more would enroll but that “a number of people actually did not want the injection or were not ready to think about stopping.” Still, the 18% enrollment is “a major improvement,” considering that no attempt was made to initiate treatment with naltrexone prior to the study. Oral naltrexone, rather than the injection, could be offered to improve participation, but oral naltrexone has to be taken daily.

She said a larger study is planned at UCSF and that other institutions are interested in starting a similar program.

“When someone is in the ED for an AUD-related issue, it can serve as a turning point for them in some cases,” she said.

Erik S. Anderson, MD, associate research director at Oakland, Calif.–based Alameda Health System, who has studied naltrexone in the ED, said the findings dovetail with what his team has found at his center. He added that psychosocial support is important as well and that his team has found that navigation services are the most important factor in connecting patients with follow-up care – even more so than providing medications.

“In my mind, this is a situation where we have treatment options and approaches that work, and it’s really about implementing these services in a novel care setting,” he said. “ED patients are at higher risk of complications for AUD simply because they are in the ED in the first place – initiating AUD treatment in this setting is the right thing to do.”

Dr. Raven and Dr. Anderson disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Men with early rheumatoid arthritis who had previously never been treated with disease-modifying antirheumatic drugs (DMARDs) achieved remission significantly more often than women when given the interleukin (IL)-6 inhibitor tocilizumab (Actemra), according to new findings published in The Lancet Rheumatology.

Researchers also found that men had higher rates of remission than women when treated with certolizumab pegol (Cimzia), abatacept (Orencia), or conventional synthetic DMARDs, but the differences were not statistically significant.

Lend_Kristina_SWEDEN_web.jpg

The findings are based on a post-hoc analysis of data from the randomized, controlled, phase 4 NORD-STAR trial performed across Scandinavia, Iceland, and the Netherlands that is believed to be the first study on treatment-naive patients to specifically analyze the interaction between sex and treatment using interaction terms. In the study, outcomes for men versus women were compared within each treatment group and also to the conventional treatment arm used as the reference group.

“Our findings could provide guidance about the optimal treatment choice for DMARD-naive men and women with early RA,” said first author Kristina Lend, MSc, research assistant at the Karolinska Institute, Stockholm, and PhD student at Amsterdam University Medical Center.

Researchers enrolled 812 patients between 2012 and 2018 and randomly assigned them to receive:

• Conventional treatment involving methotrexate plus prednisolone tapered from 20 mg per day to 5 mg per day within 9 weeks or methotrexate plus sulfasalazine (2 g per day), hydroxychloroquine (35 mg/kg per week or 200 mg per day), and intra-articular glucocorticoids in the swollen joint (maximally four joints and 80 mg per visit);
• the tumor necrosis factor (TNF) inhibitor certolizumab pegol with methotrexate;
• the T-cell co-stimulation modulator abatacept with methotrexate; or
• tocilizumab with methotrexate.

All of the patients were newly diagnosed, with symptoms for less than 24 months, and they had never taken a DMARD. Researchers used the Clinical Disease Activity Index (CDAI) as the primary tool for assessing remission. Patients started oral methotrexate initially at 10-15 mg per week and escalated within 4 weeks to a target dose of 25 mg per week.

In all groups, men achieved remission after 24 weeks at higher rates than women: 55% compared with 50% in the conventional arm; 57% vs. 52% with certolizumab pegol; 65% vs. 51% with abatacept; and 61% vs. 40% with tocilizumab. But in most cases, the 95% confidence intervals overlapped for men and women, meaning the differences didn’t reach statistical significance.

However, in the tocilizumab group, the difference was significant.

Ms. Lend said it was interesting to see this difference with tocilizumab. The drug is known to reduce acute-phase reactants, such as C-reactive protein (CRP). But the CDAI doesn’t take CRP or other acute phase reactants into account. Both men and women taking tocilizumab had significant reductions in CRP, and yet men ultimately did much better on the drug according to the CDAI, as well as other scales, such as the Disease Activity Score in 28 joints and Simplified Disease Activity Index.

Women in the conventional treatment arm actually achieved remission more often, at least in absolute numbers, than did women taking tocilizumab.

“It was surprising to see that men on tocilizumab treatment achieved higher remission rates than men in conventional treatment while women in tocilizumab treatment achieved lower remission rates than women in conventional treatment,” she said.

Several factors could account for the differences in remission, she said. Subjective components when assessing remission – such as tender joint counts and a patient’s own assessment of their disease activity – tend to be higher for women. Underlying biological mechanisms can play a role as well, with evidence suggesting that gonadal hormone concentrations modulate the immune system and affect pain signaling, influencing how the disease is experienced, she said.

Findings such as these could lead to a redrafting of treatment recommendations, Ms. Lend suggested.

“Conventional treatment is currently recommended over tocilizumab and other biologics for DMARD-naive men and women with early RA,” she said. “We do feel that the overall results of the NORD-STAR trial could lead to a reassessment of these recommendations, and that more personalized treatment decisions will become the standard.”

In an accompanying editorial, Alexandre Sepriano, MD, PhD, a rheumatologist at Hospital Egaz Moniz in Lisbon, and Elena Nikiphorou, MD, consultant rheumatologist at King’s College London, said the analysis was generally well-designed, although perhaps too small.

“The NORD-STAR trial, compared to other studies, comes the closest to answering the question at hand,” they wrote. “A fair conclusion is that (with the exception of tocilizumab) men and women respond similarly to biological DMARDs compared with conventional therapy. If true, this is reassuring news both to patients and clinicians.”

They cautioned that the study was “probably underpowered” to answer the question authoritatively.

“Despite this, the study provides useful insights into sex-driven responses to treatment,” they said. “Differences in methodological and analytical approaches will need to be considered in studies with similar intentions when interpreting the findings.”

Fritsch_Stork_Ruth_AUSTRIA_web.jpg

Ruth Fritsch-Stork, MD, PhD, professor of rheumatology at Sigmund Freud University in Vienna, who has studied sex and RA treatment in the Austrian BIOREG registry, said the findings are an important contribution to the literature.

“I think it is a very interesting paper, as little literature has been published about sex differences in RA patients regarding therapy,” she said. “And the little that is known is ambiguous. So this paper is a badly needed piece in the puzzle of treatment response in RA.”

She said she wondered how much these findings will be applicable to typical clinical scenarios, in which tocilizumab is usually at least a second-line therapy, after use of conventional synthetic DMARDs – and often after anti-TNF therapy as well. But this study population was DMARD naive.

“Also, the literature usually describes a better outcome in men for anti-TNF, which was not seen here,” she added.

“As the effect of tocilizumab seems to be greater in men not only in remission rates, but also in infection rates, I do believe an effect on the IL-6 signaling and immunological sequelae to be the underlying factor,” Dr. Fritsch-Stork said. “However, I agree with the authors that unknown, noninflammatory, sex-dependent effects on pain sensation might play a role.”

Even though the applicability of the study isn’t clear, she said, “it is important information for future investigations.”

Ms. Lend and Dr. Fritsch-Stork reported no relevant financial disclosures. Dr. Sepriano reported financial relationships with UCB, Novartis, and Lilly. Dr. Nikiphorou reported financial relationships with Pfizer, Gilead, Galapagos, Lilly, and Fresenius.

Men with early rheumatoid arthritis who had previously never been treated with disease-modifying antirheumatic drugs (DMARDs) achieved remission significantly more often than women when given the interleukin (IL)-6 inhibitor tocilizumab (Actemra), according to new findings published in The Lancet Rheumatology.

Researchers also found that men had higher rates of remission than women when treated with certolizumab pegol (Cimzia), abatacept (Orencia), or conventional synthetic DMARDs, but the differences were not statistically significant.

Lend_Kristina_SWEDEN_web.jpg

The findings are based on a post-hoc analysis of data from the randomized, controlled, phase 4 NORD-STAR trial performed across Scandinavia, Iceland, and the Netherlands that is believed to be the first study on treatment-naive patients to specifically analyze the interaction between sex and treatment using interaction terms. In the study, outcomes for men versus women were compared within each treatment group and also to the conventional treatment arm used as the reference group.

“Our findings could provide guidance about the optimal treatment choice for DMARD-naive men and women with early RA,” said first author Kristina Lend, MSc, research assistant at the Karolinska Institute, Stockholm, and PhD student at Amsterdam University Medical Center.

Researchers enrolled 812 patients between 2012 and 2018 and randomly assigned them to receive:

• Conventional treatment involving methotrexate plus prednisolone tapered from 20 mg per day to 5 mg per day within 9 weeks or methotrexate plus sulfasalazine (2 g per day), hydroxychloroquine (35 mg/kg per week or 200 mg per day), and intra-articular glucocorticoids in the swollen joint (maximally four joints and 80 mg per visit);
• the tumor necrosis factor (TNF) inhibitor certolizumab pegol with methotrexate;
• the T-cell co-stimulation modulator abatacept with methotrexate; or
• tocilizumab with methotrexate.

All of the patients were newly diagnosed, with symptoms for less than 24 months, and they had never taken a DMARD. Researchers used the Clinical Disease Activity Index (CDAI) as the primary tool for assessing remission. Patients started oral methotrexate initially at 10-15 mg per week and escalated within 4 weeks to a target dose of 25 mg per week.

In all groups, men achieved remission after 24 weeks at higher rates than women: 55% compared with 50% in the conventional arm; 57% vs. 52% with certolizumab pegol; 65% vs. 51% with abatacept; and 61% vs. 40% with tocilizumab. But in most cases, the 95% confidence intervals overlapped for men and women, meaning the differences didn’t reach statistical significance.

However, in the tocilizumab group, the difference was significant.

Ms. Lend said it was interesting to see this difference with tocilizumab. The drug is known to reduce acute-phase reactants, such as C-reactive protein (CRP). But the CDAI doesn’t take CRP or other acute phase reactants into account. Both men and women taking tocilizumab had significant reductions in CRP, and yet men ultimately did much better on the drug according to the CDAI, as well as other scales, such as the Disease Activity Score in 28 joints and Simplified Disease Activity Index.

Women in the conventional treatment arm actually achieved remission more often, at least in absolute numbers, than did women taking tocilizumab.

“It was surprising to see that men on tocilizumab treatment achieved higher remission rates than men in conventional treatment while women in tocilizumab treatment achieved lower remission rates than women in conventional treatment,” she said.

Several factors could account for the differences in remission, she said. Subjective components when assessing remission – such as tender joint counts and a patient’s own assessment of their disease activity – tend to be higher for women. Underlying biological mechanisms can play a role as well, with evidence suggesting that gonadal hormone concentrations modulate the immune system and affect pain signaling, influencing how the disease is experienced, she said.

Findings such as these could lead to a redrafting of treatment recommendations, Ms. Lend suggested.

“Conventional treatment is currently recommended over tocilizumab and other biologics for DMARD-naive men and women with early RA,” she said. “We do feel that the overall results of the NORD-STAR trial could lead to a reassessment of these recommendations, and that more personalized treatment decisions will become the standard.”

In an accompanying editorial, Alexandre Sepriano, MD, PhD, a rheumatologist at Hospital Egaz Moniz in Lisbon, and Elena Nikiphorou, MD, consultant rheumatologist at King’s College London, said the analysis was generally well-designed, although perhaps too small.

“The NORD-STAR trial, compared to other studies, comes the closest to answering the question at hand,” they wrote. “A fair conclusion is that (with the exception of tocilizumab) men and women respond similarly to biological DMARDs compared with conventional therapy. If true, this is reassuring news both to patients and clinicians.”

They cautioned that the study was “probably underpowered” to answer the question authoritatively.

“Despite this, the study provides useful insights into sex-driven responses to treatment,” they said. “Differences in methodological and analytical approaches will need to be considered in studies with similar intentions when interpreting the findings.”

Fritsch_Stork_Ruth_AUSTRIA_web.jpg

Ruth Fritsch-Stork, MD, PhD, professor of rheumatology at Sigmund Freud University in Vienna, who has studied sex and RA treatment in the Austrian BIOREG registry, said the findings are an important contribution to the literature.

“I think it is a very interesting paper, as little literature has been published about sex differences in RA patients regarding therapy,” she said. “And the little that is known is ambiguous. So this paper is a badly needed piece in the puzzle of treatment response in RA.”

She said she wondered how much these findings will be applicable to typical clinical scenarios, in which tocilizumab is usually at least a second-line therapy, after use of conventional synthetic DMARDs – and often after anti-TNF therapy as well. But this study population was DMARD naive.

“Also, the literature usually describes a better outcome in men for anti-TNF, which was not seen here,” she added.

“As the effect of tocilizumab seems to be greater in men not only in remission rates, but also in infection rates, I do believe an effect on the IL-6 signaling and immunological sequelae to be the underlying factor,” Dr. Fritsch-Stork said. “However, I agree with the authors that unknown, noninflammatory, sex-dependent effects on pain sensation might play a role.”

Even though the applicability of the study isn’t clear, she said, “it is important information for future investigations.”

Ms. Lend and Dr. Fritsch-Stork reported no relevant financial disclosures. Dr. Sepriano reported financial relationships with UCB, Novartis, and Lilly. Dr. Nikiphorou reported financial relationships with Pfizer, Gilead, Galapagos, Lilly, and Fresenius.

Men with early rheumatoid arthritis who had previously never been treated with disease-modifying antirheumatic drugs (DMARDs) achieved remission significantly more often than women when given the interleukin (IL)-6 inhibitor tocilizumab (Actemra), according to new findings published in The Lancet Rheumatology.

Researchers also found that men had higher rates of remission than women when treated with certolizumab pegol (Cimzia), abatacept (Orencia), or conventional synthetic DMARDs, but the differences were not statistically significant.

Lend_Kristina_SWEDEN_web.jpg

The findings are based on a post-hoc analysis of data from the randomized, controlled, phase 4 NORD-STAR trial performed across Scandinavia, Iceland, and the Netherlands that is believed to be the first study on treatment-naive patients to specifically analyze the interaction between sex and treatment using interaction terms. In the study, outcomes for men versus women were compared within each treatment group and also to the conventional treatment arm used as the reference group.

“Our findings could provide guidance about the optimal treatment choice for DMARD-naive men and women with early RA,” said first author Kristina Lend, MSc, research assistant at the Karolinska Institute, Stockholm, and PhD student at Amsterdam University Medical Center.

Researchers enrolled 812 patients between 2012 and 2018 and randomly assigned them to receive:

• Conventional treatment involving methotrexate plus prednisolone tapered from 20 mg per day to 5 mg per day within 9 weeks or methotrexate plus sulfasalazine (2 g per day), hydroxychloroquine (35 mg/kg per week or 200 mg per day), and intra-articular glucocorticoids in the swollen joint (maximally four joints and 80 mg per visit);
• the tumor necrosis factor (TNF) inhibitor certolizumab pegol with methotrexate;
• the T-cell co-stimulation modulator abatacept with methotrexate; or
• tocilizumab with methotrexate.

All of the patients were newly diagnosed, with symptoms for less than 24 months, and they had never taken a DMARD. Researchers used the Clinical Disease Activity Index (CDAI) as the primary tool for assessing remission. Patients started oral methotrexate initially at 10-15 mg per week and escalated within 4 weeks to a target dose of 25 mg per week.

In all groups, men achieved remission after 24 weeks at higher rates than women: 55% compared with 50% in the conventional arm; 57% vs. 52% with certolizumab pegol; 65% vs. 51% with abatacept; and 61% vs. 40% with tocilizumab. But in most cases, the 95% confidence intervals overlapped for men and women, meaning the differences didn’t reach statistical significance.

However, in the tocilizumab group, the difference was significant.

Ms. Lend said it was interesting to see this difference with tocilizumab. The drug is known to reduce acute-phase reactants, such as C-reactive protein (CRP). But the CDAI doesn’t take CRP or other acute phase reactants into account. Both men and women taking tocilizumab had significant reductions in CRP, and yet men ultimately did much better on the drug according to the CDAI, as well as other scales, such as the Disease Activity Score in 28 joints and Simplified Disease Activity Index.

Women in the conventional treatment arm actually achieved remission more often, at least in absolute numbers, than did women taking tocilizumab.

“It was surprising to see that men on tocilizumab treatment achieved higher remission rates than men in conventional treatment while women in tocilizumab treatment achieved lower remission rates than women in conventional treatment,” she said.

Several factors could account for the differences in remission, she said. Subjective components when assessing remission – such as tender joint counts and a patient’s own assessment of their disease activity – tend to be higher for women. Underlying biological mechanisms can play a role as well, with evidence suggesting that gonadal hormone concentrations modulate the immune system and affect pain signaling, influencing how the disease is experienced, she said.

Findings such as these could lead to a redrafting of treatment recommendations, Ms. Lend suggested.

“Conventional treatment is currently recommended over tocilizumab and other biologics for DMARD-naive men and women with early RA,” she said. “We do feel that the overall results of the NORD-STAR trial could lead to a reassessment of these recommendations, and that more personalized treatment decisions will become the standard.”

In an accompanying editorial, Alexandre Sepriano, MD, PhD, a rheumatologist at Hospital Egaz Moniz in Lisbon, and Elena Nikiphorou, MD, consultant rheumatologist at King’s College London, said the analysis was generally well-designed, although perhaps too small.

“The NORD-STAR trial, compared to other studies, comes the closest to answering the question at hand,” they wrote. “A fair conclusion is that (with the exception of tocilizumab) men and women respond similarly to biological DMARDs compared with conventional therapy. If true, this is reassuring news both to patients and clinicians.”

They cautioned that the study was “probably underpowered” to answer the question authoritatively.

“Despite this, the study provides useful insights into sex-driven responses to treatment,” they said. “Differences in methodological and analytical approaches will need to be considered in studies with similar intentions when interpreting the findings.”

Fritsch_Stork_Ruth_AUSTRIA_web.jpg

Ruth Fritsch-Stork, MD, PhD, professor of rheumatology at Sigmund Freud University in Vienna, who has studied sex and RA treatment in the Austrian BIOREG registry, said the findings are an important contribution to the literature.

“I think it is a very interesting paper, as little literature has been published about sex differences in RA patients regarding therapy,” she said. “And the little that is known is ambiguous. So this paper is a badly needed piece in the puzzle of treatment response in RA.”

She said she wondered how much these findings will be applicable to typical clinical scenarios, in which tocilizumab is usually at least a second-line therapy, after use of conventional synthetic DMARDs – and often after anti-TNF therapy as well. But this study population was DMARD naive.

“Also, the literature usually describes a better outcome in men for anti-TNF, which was not seen here,” she added.

“As the effect of tocilizumab seems to be greater in men not only in remission rates, but also in infection rates, I do believe an effect on the IL-6 signaling and immunological sequelae to be the underlying factor,” Dr. Fritsch-Stork said. “However, I agree with the authors that unknown, noninflammatory, sex-dependent effects on pain sensation might play a role.”

Even though the applicability of the study isn’t clear, she said, “it is important information for future investigations.”

Ms. Lend and Dr. Fritsch-Stork reported no relevant financial disclosures. Dr. Sepriano reported financial relationships with UCB, Novartis, and Lilly. Dr. Nikiphorou reported financial relationships with Pfizer, Gilead, Galapagos, Lilly, and Fresenius.

Too often, when patients come to see Tejaswini Kulkarni, MD, with shortness of breath and cough and are diagnosed with interstitial lung disease (ILD), they are past the point when treatments would most benefit them.

“There is definitely a delay from the time of symptom onset to the time that they are even evaluated for ILD,” said Dr. Kulkarni of the department of pulmonary, allergy and critical care medicine at the University of Alabama, Birmingham. “Some patients have had a significant loss of lung function by the time they come to see us. By that point we are limited by what treatment options we can offer.”

Kulkarni_Tejaswini_Alabama_web.jpg

Interstitial lung disease is an umbrella term for a group of disorders involving progressive scarring of the lungs – typically irreversible – usually caused by long-term exposure to hazardous materials or by autoimmune effects. It includes idiopathic pulmonary fibrosis (IPF), a disease that is fairly rare but which has therapy options that can be effective if caught early enough. The term pulmonary fibrosis refers to lung scarring. Another type of ILD is pulmonary sarcoidosis, in which small clumps of immune cells form in the lungs in an immune response sometimes following an environmental trigger, and can lead to lung scarring if it doesn’t resolve.

Cases of ILD appear to be on the rise, and COVID-19 has made diagnosing it more complicated. One study found the prevalence of ILD and pulmonary sarcoidosis in high-income countries was about 122 of every 100,000 people in 1990 and rose to about 198 of every 100,000 people in 2017. The data were pulled from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. Globally, the researchers found a prevalence of 62 per 100,000 in 1990, compared with 82 per 100,000 in 2017.

If all of a patient’s symptoms have appeared post COVID and a physician is seeing a patient within 4-6 weeks of COVID symptoms, it is likely that the symptoms are COVID related. But a full work-up is recommended if a patient has lung crackles, which are an indicator of lung scarring, she said.

“The patterns that are seen on CT scan for COVID pneumonia are very distinct from what we expect to see with idiopathic pulmonary fibrosis,” Dr. Kulkarni said. “Putting all this information together is what is important to differentiate it from COVID pneumonia, as well as other types of ILD.”

A study published earlier this year found similarities between COVID-19 and IPF in gene expression, their IL-15-heavy cytokine storms, and the type of damage to alveolar cells. Both might be driven by endoplasmic reticulum stress, they found.

“COVID-19 resembles IPF at a fundamental level,” they wrote.

Jeffrey Horowitz, MD, a pulmonologist and professor of medicine at the Ohio State University, said the need for early diagnosis is in part a function of the therapies available for ILD.

“They don’t make the lung function better,” he said. “So delays in diagnosis mean that there’s the possibility of underlying progression for months, or sometimes years, before the diagnosis is recognized.”

In an area in which diagnosis is delayed and the prognosis is dire – 3-5 years in untreated patients after diagnosis – “there’s a tremendous amount of nihilism out there” among patients, he said.

He said patients with long-term shortness of breath and unexplained cough are often told they have asthma and are prescribed inhalers, but then further assessment isn’t performed when those don’t work.
 

Diagnosing ILD in primary care

Many primary care physicians feel ill-equipped to discuss IPF. More than a dozen physicians contacted for this piece to talk about ILD either did not respond, or said they felt unqualified to respond to questions on the disease.

“Not my area of expertise” and “I don’t think I’m the right person for this discussion” were two of the responses provided to this news organization.

“For some reason, in the world of primary care, it seems like there’s an impediment to getting pulmonary function studies,” Dr. Horowitz said. “Anybody who has a persistent ongoing prolonged unexplained shortness of breath and cough should have pulmonary function studies done.”

Listening to the lungs alone might not be enough, he said. There might be no clear sign in the case of early pulmonary fibrosis, he said.

“There’s the textbook description of these Velcro-sounding crackles, but sometimes it’s very subtle,” he said. “And unless you’re listening very carefully it can easily be missed by somebody who has a busy practice, or it’s loud.”

William E. Golden, MD, professor of medicine and public health at the University of Arkansas, Little Rock, is the sole primary care physician contacted for this piece who spoke with authority on ILD.

For cases of suspected ILD, internist Dr. Golden, who also serves on the editorial advisory board of Internal Medicine News, suggested ordering a test for diffusing capacity for carbon monoxide (DLCO), which will be low in the case of IPF, along with a fine-cut lung CT scan to assess ongoing fibrotic changes.

It’s “not that difficult, but you need to have an index of suspicion for the diagnosis,” he said.
 

New initiative for helping diagnose ILD

Dr. Kulkarni is a committee member for a new effort under way to try to get patients with ILD diagnosed earlier.

The initiative, called Bridging Specialties: Timely Diagnosis for ILD Patients, has already produced an introductory podcast and a white paper on the effort, and its rationale is expected to be released soon, according to Dr. Kulkarni and her fellow committee members.

The American College of Chest Physicians and the Three Lakes Foundation – a foundation dedicated to pulmonary fibrosis awareness and research – are working together on this initiative. They plan to put together a suite of resources, to be gradually rolled out on the college’s website, to raise awareness about the importance of early diagnosis of ILD.

The full toolkit, expected to be rolled out over the next 12 months, will include a series of podcasts and resources on how to get patients diagnosed earlier and steps to take in cases of suspected ILD, Dr. Kulkarni said.

“The goal would be to try to increase awareness about the disease so that people start thinking more about it up front – and not after we’ve ruled out everything else,” she said. The main audience will be primary care providers, but patients and community pulmonologists would likely also benefit from the resources, the committee members said.

The urgency of the initiative stems from the way ILD treatments work. They are antifibrotic, meaning they help prevent scar tissue from forming, but they can’t reverse scar tissue that has already formed. If scarring is severe, the only option might be a lung transplant, and, since the average age at ILD diagnosis is in the 60s, many patients have comorbidities that make them ineligible for transplant. According to the Global Burden of Disease Study mentioned earlier, the death rate per 100,000 people with ILD was 1.93 in 2017.

“The longer we take to diagnose it, the more chance that inflammation will become scar tissue,” Dr. Kularni explained.

Lago_William_Cleveland_web.jpg

William Lago, MD, another member of the committee and a family physician, said identifying ILD early is not a straightforward matter .

“When they first present, it’s hard to pick up,” said Dr. Lago, who is also a staff physician at Cleveland Clinic’s Wooster Family Health Center and medical director of the COVID Recover Clinic there. “Many of them, even themselves, will discount the symptoms.”

Dr. Lago said that patients might resist having a work-up even when a primary care physician identifies symptoms as possible ILD. In rural settings, they might have to travel quite a distance for a CT scan or other necessary evaluations, or they might just not think the symptoms are serious enough.

“Most of the time when I’ve picked up some of my pulmonary fibrosis patients, it’s been incidentally while they’re in the office for other things,” he said. He often has to “push the issue” for further work-up, he said.

The overlap of shortness of breath and cough with other, much more common disorders, such as heart disease or chronic obstructive pulmonary disease (COPD), make ILD diagnosis a challenge, he said.

“For most of us, we’ve got sometimes 10 or 15 minutes with a patient who’s presenting with 5-6 different problems. And the shortness of breath or the occasional cough – that they think is nothing – is probably the least of those,” Dr. Lago said.

Dr. Golden said he suspected a tool like the one being developed by CHEST to be useful for some and not useful for others. He added that “no one has the time to spend on that kind of thing.”

Instead, he suggested just reinforcing what the core symptoms are and what the core testing is, “to make people think about it.”

Dr. Horowitiz seemed more optimistic about the likelihood of the CHEST tool being utilized to diagnose ILD.

Whether and how he would use the CHEST resource will depend on the final form it takes, Dr. Horowitz said. It’s encouraging that it’s being put together by a credible source, he added.

Dr. Kulkarni reported financial relationships with Boehringer Ingelheim, Aluda Pharmaceuticals and PureTech Lyt-100 Inc. Dr. Lago, Dr. Horowitz, and Dr. Golden reported no relevant disclosures.

Katie Lennon contributed to this report.

Too often, when patients come to see Tejaswini Kulkarni, MD, with shortness of breath and cough and are diagnosed with interstitial lung disease (ILD), they are past the point when treatments would most benefit them.

“There is definitely a delay from the time of symptom onset to the time that they are even evaluated for ILD,” said Dr. Kulkarni of the department of pulmonary, allergy and critical care medicine at the University of Alabama, Birmingham. “Some patients have had a significant loss of lung function by the time they come to see us. By that point we are limited by what treatment options we can offer.”

Kulkarni_Tejaswini_Alabama_web.jpg

Interstitial lung disease is an umbrella term for a group of disorders involving progressive scarring of the lungs – typically irreversible – usually caused by long-term exposure to hazardous materials or by autoimmune effects. It includes idiopathic pulmonary fibrosis (IPF), a disease that is fairly rare but which has therapy options that can be effective if caught early enough. The term pulmonary fibrosis refers to lung scarring. Another type of ILD is pulmonary sarcoidosis, in which small clumps of immune cells form in the lungs in an immune response sometimes following an environmental trigger, and can lead to lung scarring if it doesn’t resolve.

Cases of ILD appear to be on the rise, and COVID-19 has made diagnosing it more complicated. One study found the prevalence of ILD and pulmonary sarcoidosis in high-income countries was about 122 of every 100,000 people in 1990 and rose to about 198 of every 100,000 people in 2017. The data were pulled from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. Globally, the researchers found a prevalence of 62 per 100,000 in 1990, compared with 82 per 100,000 in 2017.

If all of a patient’s symptoms have appeared post COVID and a physician is seeing a patient within 4-6 weeks of COVID symptoms, it is likely that the symptoms are COVID related. But a full work-up is recommended if a patient has lung crackles, which are an indicator of lung scarring, she said.

“The patterns that are seen on CT scan for COVID pneumonia are very distinct from what we expect to see with idiopathic pulmonary fibrosis,” Dr. Kulkarni said. “Putting all this information together is what is important to differentiate it from COVID pneumonia, as well as other types of ILD.”

A study published earlier this year found similarities between COVID-19 and IPF in gene expression, their IL-15-heavy cytokine storms, and the type of damage to alveolar cells. Both might be driven by endoplasmic reticulum stress, they found.

“COVID-19 resembles IPF at a fundamental level,” they wrote.

Jeffrey Horowitz, MD, a pulmonologist and professor of medicine at the Ohio State University, said the need for early diagnosis is in part a function of the therapies available for ILD.

“They don’t make the lung function better,” he said. “So delays in diagnosis mean that there’s the possibility of underlying progression for months, or sometimes years, before the diagnosis is recognized.”

In an area in which diagnosis is delayed and the prognosis is dire – 3-5 years in untreated patients after diagnosis – “there’s a tremendous amount of nihilism out there” among patients, he said.

He said patients with long-term shortness of breath and unexplained cough are often told they have asthma and are prescribed inhalers, but then further assessment isn’t performed when those don’t work.
 

Diagnosing ILD in primary care

Many primary care physicians feel ill-equipped to discuss IPF. More than a dozen physicians contacted for this piece to talk about ILD either did not respond, or said they felt unqualified to respond to questions on the disease.

“Not my area of expertise” and “I don’t think I’m the right person for this discussion” were two of the responses provided to this news organization.

“For some reason, in the world of primary care, it seems like there’s an impediment to getting pulmonary function studies,” Dr. Horowitz said. “Anybody who has a persistent ongoing prolonged unexplained shortness of breath and cough should have pulmonary function studies done.”

Listening to the lungs alone might not be enough, he said. There might be no clear sign in the case of early pulmonary fibrosis, he said.

“There’s the textbook description of these Velcro-sounding crackles, but sometimes it’s very subtle,” he said. “And unless you’re listening very carefully it can easily be missed by somebody who has a busy practice, or it’s loud.”

William E. Golden, MD, professor of medicine and public health at the University of Arkansas, Little Rock, is the sole primary care physician contacted for this piece who spoke with authority on ILD.

For cases of suspected ILD, internist Dr. Golden, who also serves on the editorial advisory board of Internal Medicine News, suggested ordering a test for diffusing capacity for carbon monoxide (DLCO), which will be low in the case of IPF, along with a fine-cut lung CT scan to assess ongoing fibrotic changes.

It’s “not that difficult, but you need to have an index of suspicion for the diagnosis,” he said.
 

New initiative for helping diagnose ILD

Dr. Kulkarni is a committee member for a new effort under way to try to get patients with ILD diagnosed earlier.

The initiative, called Bridging Specialties: Timely Diagnosis for ILD Patients, has already produced an introductory podcast and a white paper on the effort, and its rationale is expected to be released soon, according to Dr. Kulkarni and her fellow committee members.

The American College of Chest Physicians and the Three Lakes Foundation – a foundation dedicated to pulmonary fibrosis awareness and research – are working together on this initiative. They plan to put together a suite of resources, to be gradually rolled out on the college’s website, to raise awareness about the importance of early diagnosis of ILD.

The full toolkit, expected to be rolled out over the next 12 months, will include a series of podcasts and resources on how to get patients diagnosed earlier and steps to take in cases of suspected ILD, Dr. Kulkarni said.

“The goal would be to try to increase awareness about the disease so that people start thinking more about it up front – and not after we’ve ruled out everything else,” she said. The main audience will be primary care providers, but patients and community pulmonologists would likely also benefit from the resources, the committee members said.

The urgency of the initiative stems from the way ILD treatments work. They are antifibrotic, meaning they help prevent scar tissue from forming, but they can’t reverse scar tissue that has already formed. If scarring is severe, the only option might be a lung transplant, and, since the average age at ILD diagnosis is in the 60s, many patients have comorbidities that make them ineligible for transplant. According to the Global Burden of Disease Study mentioned earlier, the death rate per 100,000 people with ILD was 1.93 in 2017.

“The longer we take to diagnose it, the more chance that inflammation will become scar tissue,” Dr. Kularni explained.

Lago_William_Cleveland_web.jpg

William Lago, MD, another member of the committee and a family physician, said identifying ILD early is not a straightforward matter .

“When they first present, it’s hard to pick up,” said Dr. Lago, who is also a staff physician at Cleveland Clinic’s Wooster Family Health Center and medical director of the COVID Recover Clinic there. “Many of them, even themselves, will discount the symptoms.”

Dr. Lago said that patients might resist having a work-up even when a primary care physician identifies symptoms as possible ILD. In rural settings, they might have to travel quite a distance for a CT scan or other necessary evaluations, or they might just not think the symptoms are serious enough.

“Most of the time when I’ve picked up some of my pulmonary fibrosis patients, it’s been incidentally while they’re in the office for other things,” he said. He often has to “push the issue” for further work-up, he said.

The overlap of shortness of breath and cough with other, much more common disorders, such as heart disease or chronic obstructive pulmonary disease (COPD), make ILD diagnosis a challenge, he said.

“For most of us, we’ve got sometimes 10 or 15 minutes with a patient who’s presenting with 5-6 different problems. And the shortness of breath or the occasional cough – that they think is nothing – is probably the least of those,” Dr. Lago said.

Dr. Golden said he suspected a tool like the one being developed by CHEST to be useful for some and not useful for others. He added that “no one has the time to spend on that kind of thing.”

Instead, he suggested just reinforcing what the core symptoms are and what the core testing is, “to make people think about it.”

Dr. Horowitiz seemed more optimistic about the likelihood of the CHEST tool being utilized to diagnose ILD.

Whether and how he would use the CHEST resource will depend on the final form it takes, Dr. Horowitz said. It’s encouraging that it’s being put together by a credible source, he added.

Dr. Kulkarni reported financial relationships with Boehringer Ingelheim, Aluda Pharmaceuticals and PureTech Lyt-100 Inc. Dr. Lago, Dr. Horowitz, and Dr. Golden reported no relevant disclosures.

Katie Lennon contributed to this report.

Too often, when patients come to see Tejaswini Kulkarni, MD, with shortness of breath and cough and are diagnosed with interstitial lung disease (ILD), they are past the point when treatments would most benefit them.

“There is definitely a delay from the time of symptom onset to the time that they are even evaluated for ILD,” said Dr. Kulkarni of the department of pulmonary, allergy and critical care medicine at the University of Alabama, Birmingham. “Some patients have had a significant loss of lung function by the time they come to see us. By that point we are limited by what treatment options we can offer.”

Kulkarni_Tejaswini_Alabama_web.jpg

Interstitial lung disease is an umbrella term for a group of disorders involving progressive scarring of the lungs – typically irreversible – usually caused by long-term exposure to hazardous materials or by autoimmune effects. It includes idiopathic pulmonary fibrosis (IPF), a disease that is fairly rare but which has therapy options that can be effective if caught early enough. The term pulmonary fibrosis refers to lung scarring. Another type of ILD is pulmonary sarcoidosis, in which small clumps of immune cells form in the lungs in an immune response sometimes following an environmental trigger, and can lead to lung scarring if it doesn’t resolve.

Cases of ILD appear to be on the rise, and COVID-19 has made diagnosing it more complicated. One study found the prevalence of ILD and pulmonary sarcoidosis in high-income countries was about 122 of every 100,000 people in 1990 and rose to about 198 of every 100,000 people in 2017. The data were pulled from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. Globally, the researchers found a prevalence of 62 per 100,000 in 1990, compared with 82 per 100,000 in 2017.

If all of a patient’s symptoms have appeared post COVID and a physician is seeing a patient within 4-6 weeks of COVID symptoms, it is likely that the symptoms are COVID related. But a full work-up is recommended if a patient has lung crackles, which are an indicator of lung scarring, she said.

“The patterns that are seen on CT scan for COVID pneumonia are very distinct from what we expect to see with idiopathic pulmonary fibrosis,” Dr. Kulkarni said. “Putting all this information together is what is important to differentiate it from COVID pneumonia, as well as other types of ILD.”

A study published earlier this year found similarities between COVID-19 and IPF in gene expression, their IL-15-heavy cytokine storms, and the type of damage to alveolar cells. Both might be driven by endoplasmic reticulum stress, they found.

“COVID-19 resembles IPF at a fundamental level,” they wrote.

Jeffrey Horowitz, MD, a pulmonologist and professor of medicine at the Ohio State University, said the need for early diagnosis is in part a function of the therapies available for ILD.

“They don’t make the lung function better,” he said. “So delays in diagnosis mean that there’s the possibility of underlying progression for months, or sometimes years, before the diagnosis is recognized.”

In an area in which diagnosis is delayed and the prognosis is dire – 3-5 years in untreated patients after diagnosis – “there’s a tremendous amount of nihilism out there” among patients, he said.

He said patients with long-term shortness of breath and unexplained cough are often told they have asthma and are prescribed inhalers, but then further assessment isn’t performed when those don’t work.
 

Diagnosing ILD in primary care

Many primary care physicians feel ill-equipped to discuss IPF. More than a dozen physicians contacted for this piece to talk about ILD either did not respond, or said they felt unqualified to respond to questions on the disease.

“Not my area of expertise” and “I don’t think I’m the right person for this discussion” were two of the responses provided to this news organization.

“For some reason, in the world of primary care, it seems like there’s an impediment to getting pulmonary function studies,” Dr. Horowitz said. “Anybody who has a persistent ongoing prolonged unexplained shortness of breath and cough should have pulmonary function studies done.”

Listening to the lungs alone might not be enough, he said. There might be no clear sign in the case of early pulmonary fibrosis, he said.

“There’s the textbook description of these Velcro-sounding crackles, but sometimes it’s very subtle,” he said. “And unless you’re listening very carefully it can easily be missed by somebody who has a busy practice, or it’s loud.”

William E. Golden, MD, professor of medicine and public health at the University of Arkansas, Little Rock, is the sole primary care physician contacted for this piece who spoke with authority on ILD.

For cases of suspected ILD, internist Dr. Golden, who also serves on the editorial advisory board of Internal Medicine News, suggested ordering a test for diffusing capacity for carbon monoxide (DLCO), which will be low in the case of IPF, along with a fine-cut lung CT scan to assess ongoing fibrotic changes.

It’s “not that difficult, but you need to have an index of suspicion for the diagnosis,” he said.
 

New initiative for helping diagnose ILD

Dr. Kulkarni is a committee member for a new effort under way to try to get patients with ILD diagnosed earlier.

The initiative, called Bridging Specialties: Timely Diagnosis for ILD Patients, has already produced an introductory podcast and a white paper on the effort, and its rationale is expected to be released soon, according to Dr. Kulkarni and her fellow committee members.

The American College of Chest Physicians and the Three Lakes Foundation – a foundation dedicated to pulmonary fibrosis awareness and research – are working together on this initiative. They plan to put together a suite of resources, to be gradually rolled out on the college’s website, to raise awareness about the importance of early diagnosis of ILD.

The full toolkit, expected to be rolled out over the next 12 months, will include a series of podcasts and resources on how to get patients diagnosed earlier and steps to take in cases of suspected ILD, Dr. Kulkarni said.

“The goal would be to try to increase awareness about the disease so that people start thinking more about it up front – and not after we’ve ruled out everything else,” she said. The main audience will be primary care providers, but patients and community pulmonologists would likely also benefit from the resources, the committee members said.

The urgency of the initiative stems from the way ILD treatments work. They are antifibrotic, meaning they help prevent scar tissue from forming, but they can’t reverse scar tissue that has already formed. If scarring is severe, the only option might be a lung transplant, and, since the average age at ILD diagnosis is in the 60s, many patients have comorbidities that make them ineligible for transplant. According to the Global Burden of Disease Study mentioned earlier, the death rate per 100,000 people with ILD was 1.93 in 2017.

“The longer we take to diagnose it, the more chance that inflammation will become scar tissue,” Dr. Kularni explained.

Lago_William_Cleveland_web.jpg

William Lago, MD, another member of the committee and a family physician, said identifying ILD early is not a straightforward matter .

“When they first present, it’s hard to pick up,” said Dr. Lago, who is also a staff physician at Cleveland Clinic’s Wooster Family Health Center and medical director of the COVID Recover Clinic there. “Many of them, even themselves, will discount the symptoms.”

Dr. Lago said that patients might resist having a work-up even when a primary care physician identifies symptoms as possible ILD. In rural settings, they might have to travel quite a distance for a CT scan or other necessary evaluations, or they might just not think the symptoms are serious enough.

“Most of the time when I’ve picked up some of my pulmonary fibrosis patients, it’s been incidentally while they’re in the office for other things,” he said. He often has to “push the issue” for further work-up, he said.

The overlap of shortness of breath and cough with other, much more common disorders, such as heart disease or chronic obstructive pulmonary disease (COPD), make ILD diagnosis a challenge, he said.

“For most of us, we’ve got sometimes 10 or 15 minutes with a patient who’s presenting with 5-6 different problems. And the shortness of breath or the occasional cough – that they think is nothing – is probably the least of those,” Dr. Lago said.

Dr. Golden said he suspected a tool like the one being developed by CHEST to be useful for some and not useful for others. He added that “no one has the time to spend on that kind of thing.”

Instead, he suggested just reinforcing what the core symptoms are and what the core testing is, “to make people think about it.”

Dr. Horowitiz seemed more optimistic about the likelihood of the CHEST tool being utilized to diagnose ILD.

Whether and how he would use the CHEST resource will depend on the final form it takes, Dr. Horowitz said. It’s encouraging that it’s being put together by a credible source, he added.

Dr. Kulkarni reported financial relationships with Boehringer Ingelheim, Aluda Pharmaceuticals and PureTech Lyt-100 Inc. Dr. Lago, Dr. Horowitz, and Dr. Golden reported no relevant disclosures.

Katie Lennon contributed to this report.

The investigational IL-6 inhibitor olokizumab fared better than placebo and was noninferior to the tumor necrosis factor inhibitor (TNFi) adalimumab (Humira) in patients with moderate to severe rheumatoid arthritis (RA) who’d had an inadequate response to methotrexate alone, according to new findings published in the New England Journal of Medicine.

The results from the phase 3, multicenter, double-blind, parallel-group, randomized, placebo- and active-comparator–controlled trial, called Clinical Rheumatoid Arthritis Development for Olokizumab (CREDO2), add to the evidence base on the drug, which was developed by R-Pharm in Russia and has been approved for use there. Last year, researchers reported results from two trials showing sustained improvements in symptoms, function, and quality of life in patients with an inadequate response to anti-TNF treatment.

smolen_josef_Vienna_web.jpg

“Once approved, olokizumab can be used in patients who have not responded well to either methotrexate or any biological disease-modifying antirheumatic drug or any JAK [Janus kinase] inhibitor in combination with methotrexate or alone,” said Josef Smolen, MD, chair of rheumatology at the Medical University of Vienna and the lead author on the study.

Researchers randomized 1,648 patients to 64 mg of olokizumab every 2 or 4 weeks, adalimumab every 2 weeks, or placebo. All patient groups continued to receive methotrexate. A total of 89.7% of the participants completed 24 weeks of treatment. By that point, 74.1% of those receiving olokizumab every 2 weeks had achieved an ACR 20 response, an improvement of at least 20% in American College of Rheumatology response criteria, including tender and swollen joints, and 71.4% in the group receiving olokizumab every 4 weeks; 69.0% in the adalimumab group; and 46.5% in the placebo group had achieved an ACR 20 response. Olokizumab benefits were also seen for Disease Activity Score in 28 joints, disability index scores, and ACR 50 responses, the researchers reported.

Approved IL-6 inhibitors tocilizumab (Actemra) and sarilumab (Kevzara) target the interleukin (IL)-6 receptor (IL-6R), but olokizumab targets a protein, glycoprotein 130 (GP130), to which the IL-6 and IL-6–receptor complex binds. This approach could offer an added benefit, Dr. Smolen said.

“Previously studied anti–IL-6 antibodies and anti–IL-6R antibodies prevent binding of IL-6 to the IL-6R,” he said. “Moreover, the amount of protein needed to inhibit IL-6 is lower compared to the approved antireceptor antibodies. Olokizumab has also been shown to be effective when given every 4 weeks in many patients, compared with the need for weekly or every-other-week applications with tocilizumab and sarilumab. From these perspectives, this novel mode of action may, indeed, provide an advantage.”

ACR 70 – an improvement of at least 70% in the ACR response criteria – was an exploratory endpoint in the trial. This response was seen in 28% of those receiving olokizumab, compared with 11% in the placebo group, but researchers cautioned that “no conclusions can be drawn from these results.”

Another drug, sirukumab, also targeted the IL-6 ligand rather than the receptor, but was rejected by regulators in 2017 because so many more deaths occurred in the treatment group than the placebo group.

Dr. Smolen noted that there are three binding sites for IL-6, but olokizumab is the first to target site 3, the binding site for GP130. Mortality concerns haven’t been seen for olokizumab. There were three serious adverse events leading to death in the olokizumab every-2-weeks group; two in the olokizumab every-4-weeks group; one in the adalimumab group; and one in the placebo group.

“The fact that olokizumab targets another site on the IL-6 molecule than sirukumab may be a reason for the difference,” Dr. Smolen said.

Still, researchers noted that the time horizon for this trial is not very long.

“The trial was conducted in a relatively small number of patients and over a short duration, especially for the assessment of rare events or events requiring longer durations of exposure,” they wrote. “Longer and larger trials are required to determine the efficacy and safety of olokizumab in patients with rheumatoid arthritis.”

Dr. Smolen said he expects R-Pharm will file for regulatory approval in the United States and Europe, outside of Russia, in the next year.

Emery_Paul_UK3_web.jpg

Paul Emery, MD, professor of rheumatology at the University of Leeds (England) who has researched IL-6 therapy in RA, said olokizumab appears to be an effective product, but its use remains a question.

“The question is where it will fit into treatment strategies,” he said. “It’ll be very interesting.”

Dr. Emery pointed out that tocilizumab, which inhibits IL-6 by blocking the IL-6 receptor, was approved in the United States at a dosage that wasn’t optimally effective after failure with TNF inhibitors (TNFi), and wondered whether olokizumab would fare differently in this regard.

While Dr. Emery said it was important that no bad safety signal has been seen, he noted that “it’s a short-term study, and you do need to see the long-term data.”

“It seems to work at both the intervals it was tested at, 2 and 4 weeks. The unknowns are whether it will be as effective as IL-6 receptor blockers in other diseases,” such as giant cell arteritis, “and early disease, and whether it will work as well post TNFi,” he said. “It could be used as first advanced therapy for people with contraindications to TNFi, but initially the majority of its use will be after TNFi, and that’s why you need to see more data on such patients.”

He added: “The final issue will be pricing. Therefore, a positive study – but much is still unknown.”

The study was supported by R-Pharm. Dr. Smolen reports financial relationships with R-Pharm, AbbVie, Janssen, Eli Lilly, Gilead, Pfizer, and other companies. Dr. Emery reports financial relationships with AbbVie, AstraZeneca, Janssen, Pfizer, Roche, and other companies, but not olokizumab manufacturer R-Pharm.

The investigational IL-6 inhibitor olokizumab fared better than placebo and was noninferior to the tumor necrosis factor inhibitor (TNFi) adalimumab (Humira) in patients with moderate to severe rheumatoid arthritis (RA) who’d had an inadequate response to methotrexate alone, according to new findings published in the New England Journal of Medicine.

The results from the phase 3, multicenter, double-blind, parallel-group, randomized, placebo- and active-comparator–controlled trial, called Clinical Rheumatoid Arthritis Development for Olokizumab (CREDO2), add to the evidence base on the drug, which was developed by R-Pharm in Russia and has been approved for use there. Last year, researchers reported results from two trials showing sustained improvements in symptoms, function, and quality of life in patients with an inadequate response to anti-TNF treatment.

smolen_josef_Vienna_web.jpg

“Once approved, olokizumab can be used in patients who have not responded well to either methotrexate or any biological disease-modifying antirheumatic drug or any JAK [Janus kinase] inhibitor in combination with methotrexate or alone,” said Josef Smolen, MD, chair of rheumatology at the Medical University of Vienna and the lead author on the study.

Researchers randomized 1,648 patients to 64 mg of olokizumab every 2 or 4 weeks, adalimumab every 2 weeks, or placebo. All patient groups continued to receive methotrexate. A total of 89.7% of the participants completed 24 weeks of treatment. By that point, 74.1% of those receiving olokizumab every 2 weeks had achieved an ACR 20 response, an improvement of at least 20% in American College of Rheumatology response criteria, including tender and swollen joints, and 71.4% in the group receiving olokizumab every 4 weeks; 69.0% in the adalimumab group; and 46.5% in the placebo group had achieved an ACR 20 response. Olokizumab benefits were also seen for Disease Activity Score in 28 joints, disability index scores, and ACR 50 responses, the researchers reported.

Approved IL-6 inhibitors tocilizumab (Actemra) and sarilumab (Kevzara) target the interleukin (IL)-6 receptor (IL-6R), but olokizumab targets a protein, glycoprotein 130 (GP130), to which the IL-6 and IL-6–receptor complex binds. This approach could offer an added benefit, Dr. Smolen said.

“Previously studied anti–IL-6 antibodies and anti–IL-6R antibodies prevent binding of IL-6 to the IL-6R,” he said. “Moreover, the amount of protein needed to inhibit IL-6 is lower compared to the approved antireceptor antibodies. Olokizumab has also been shown to be effective when given every 4 weeks in many patients, compared with the need for weekly or every-other-week applications with tocilizumab and sarilumab. From these perspectives, this novel mode of action may, indeed, provide an advantage.”

ACR 70 – an improvement of at least 70% in the ACR response criteria – was an exploratory endpoint in the trial. This response was seen in 28% of those receiving olokizumab, compared with 11% in the placebo group, but researchers cautioned that “no conclusions can be drawn from these results.”

Another drug, sirukumab, also targeted the IL-6 ligand rather than the receptor, but was rejected by regulators in 2017 because so many more deaths occurred in the treatment group than the placebo group.

Dr. Smolen noted that there are three binding sites for IL-6, but olokizumab is the first to target site 3, the binding site for GP130. Mortality concerns haven’t been seen for olokizumab. There were three serious adverse events leading to death in the olokizumab every-2-weeks group; two in the olokizumab every-4-weeks group; one in the adalimumab group; and one in the placebo group.

“The fact that olokizumab targets another site on the IL-6 molecule than sirukumab may be a reason for the difference,” Dr. Smolen said.

Still, researchers noted that the time horizon for this trial is not very long.

“The trial was conducted in a relatively small number of patients and over a short duration, especially for the assessment of rare events or events requiring longer durations of exposure,” they wrote. “Longer and larger trials are required to determine the efficacy and safety of olokizumab in patients with rheumatoid arthritis.”

Dr. Smolen said he expects R-Pharm will file for regulatory approval in the United States and Europe, outside of Russia, in the next year.

Emery_Paul_UK3_web.jpg

Paul Emery, MD, professor of rheumatology at the University of Leeds (England) who has researched IL-6 therapy in RA, said olokizumab appears to be an effective product, but its use remains a question.

“The question is where it will fit into treatment strategies,” he said. “It’ll be very interesting.”

Dr. Emery pointed out that tocilizumab, which inhibits IL-6 by blocking the IL-6 receptor, was approved in the United States at a dosage that wasn’t optimally effective after failure with TNF inhibitors (TNFi), and wondered whether olokizumab would fare differently in this regard.

While Dr. Emery said it was important that no bad safety signal has been seen, he noted that “it’s a short-term study, and you do need to see the long-term data.”

“It seems to work at both the intervals it was tested at, 2 and 4 weeks. The unknowns are whether it will be as effective as IL-6 receptor blockers in other diseases,” such as giant cell arteritis, “and early disease, and whether it will work as well post TNFi,” he said. “It could be used as first advanced therapy for people with contraindications to TNFi, but initially the majority of its use will be after TNFi, and that’s why you need to see more data on such patients.”

He added: “The final issue will be pricing. Therefore, a positive study – but much is still unknown.”

The study was supported by R-Pharm. Dr. Smolen reports financial relationships with R-Pharm, AbbVie, Janssen, Eli Lilly, Gilead, Pfizer, and other companies. Dr. Emery reports financial relationships with AbbVie, AstraZeneca, Janssen, Pfizer, Roche, and other companies, but not olokizumab manufacturer R-Pharm.

The investigational IL-6 inhibitor olokizumab fared better than placebo and was noninferior to the tumor necrosis factor inhibitor (TNFi) adalimumab (Humira) in patients with moderate to severe rheumatoid arthritis (RA) who’d had an inadequate response to methotrexate alone, according to new findings published in the New England Journal of Medicine.

The results from the phase 3, multicenter, double-blind, parallel-group, randomized, placebo- and active-comparator–controlled trial, called Clinical Rheumatoid Arthritis Development for Olokizumab (CREDO2), add to the evidence base on the drug, which was developed by R-Pharm in Russia and has been approved for use there. Last year, researchers reported results from two trials showing sustained improvements in symptoms, function, and quality of life in patients with an inadequate response to anti-TNF treatment.

smolen_josef_Vienna_web.jpg

“Once approved, olokizumab can be used in patients who have not responded well to either methotrexate or any biological disease-modifying antirheumatic drug or any JAK [Janus kinase] inhibitor in combination with methotrexate or alone,” said Josef Smolen, MD, chair of rheumatology at the Medical University of Vienna and the lead author on the study.

Researchers randomized 1,648 patients to 64 mg of olokizumab every 2 or 4 weeks, adalimumab every 2 weeks, or placebo. All patient groups continued to receive methotrexate. A total of 89.7% of the participants completed 24 weeks of treatment. By that point, 74.1% of those receiving olokizumab every 2 weeks had achieved an ACR 20 response, an improvement of at least 20% in American College of Rheumatology response criteria, including tender and swollen joints, and 71.4% in the group receiving olokizumab every 4 weeks; 69.0% in the adalimumab group; and 46.5% in the placebo group had achieved an ACR 20 response. Olokizumab benefits were also seen for Disease Activity Score in 28 joints, disability index scores, and ACR 50 responses, the researchers reported.

Approved IL-6 inhibitors tocilizumab (Actemra) and sarilumab (Kevzara) target the interleukin (IL)-6 receptor (IL-6R), but olokizumab targets a protein, glycoprotein 130 (GP130), to which the IL-6 and IL-6–receptor complex binds. This approach could offer an added benefit, Dr. Smolen said.

“Previously studied anti–IL-6 antibodies and anti–IL-6R antibodies prevent binding of IL-6 to the IL-6R,” he said. “Moreover, the amount of protein needed to inhibit IL-6 is lower compared to the approved antireceptor antibodies. Olokizumab has also been shown to be effective when given every 4 weeks in many patients, compared with the need for weekly or every-other-week applications with tocilizumab and sarilumab. From these perspectives, this novel mode of action may, indeed, provide an advantage.”

ACR 70 – an improvement of at least 70% in the ACR response criteria – was an exploratory endpoint in the trial. This response was seen in 28% of those receiving olokizumab, compared with 11% in the placebo group, but researchers cautioned that “no conclusions can be drawn from these results.”

Another drug, sirukumab, also targeted the IL-6 ligand rather than the receptor, but was rejected by regulators in 2017 because so many more deaths occurred in the treatment group than the placebo group.

Dr. Smolen noted that there are three binding sites for IL-6, but olokizumab is the first to target site 3, the binding site for GP130. Mortality concerns haven’t been seen for olokizumab. There were three serious adverse events leading to death in the olokizumab every-2-weeks group; two in the olokizumab every-4-weeks group; one in the adalimumab group; and one in the placebo group.

“The fact that olokizumab targets another site on the IL-6 molecule than sirukumab may be a reason for the difference,” Dr. Smolen said.

Still, researchers noted that the time horizon for this trial is not very long.

“The trial was conducted in a relatively small number of patients and over a short duration, especially for the assessment of rare events or events requiring longer durations of exposure,” they wrote. “Longer and larger trials are required to determine the efficacy and safety of olokizumab in patients with rheumatoid arthritis.”

Dr. Smolen said he expects R-Pharm will file for regulatory approval in the United States and Europe, outside of Russia, in the next year.

Emery_Paul_UK3_web.jpg

Paul Emery, MD, professor of rheumatology at the University of Leeds (England) who has researched IL-6 therapy in RA, said olokizumab appears to be an effective product, but its use remains a question.

“The question is where it will fit into treatment strategies,” he said. “It’ll be very interesting.”

Dr. Emery pointed out that tocilizumab, which inhibits IL-6 by blocking the IL-6 receptor, was approved in the United States at a dosage that wasn’t optimally effective after failure with TNF inhibitors (TNFi), and wondered whether olokizumab would fare differently in this regard.

While Dr. Emery said it was important that no bad safety signal has been seen, he noted that “it’s a short-term study, and you do need to see the long-term data.”

“It seems to work at both the intervals it was tested at, 2 and 4 weeks. The unknowns are whether it will be as effective as IL-6 receptor blockers in other diseases,” such as giant cell arteritis, “and early disease, and whether it will work as well post TNFi,” he said. “It could be used as first advanced therapy for people with contraindications to TNFi, but initially the majority of its use will be after TNFi, and that’s why you need to see more data on such patients.”

He added: “The final issue will be pricing. Therefore, a positive study – but much is still unknown.”

The study was supported by R-Pharm. Dr. Smolen reports financial relationships with R-Pharm, AbbVie, Janssen, Eli Lilly, Gilead, Pfizer, and other companies. Dr. Emery reports financial relationships with AbbVie, AstraZeneca, Janssen, Pfizer, Roche, and other companies, but not olokizumab manufacturer R-Pharm.

Aiming for a disease activity target while reducing biologic therapy could be a winning approach for patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), according to the results of a new study presented at the annual European Congress of Rheumatology.

The findings show that a treat-to-target (T2T) strategy with tapering using a tumor necrosis factor (TNF) inhibitor produces results that are noninferior to a T2T strategy that doesn’t include tapering in these patients.

Michielsens_Celia_NETH_web.jpg

“Our study has for the first time shown that a treat-to-target tapering strategy is just as good as full-dose continuation, while reducing medication use substantially,” first author Celia Michielsens, MD, a PhD student and researcher at Sint Maartenskliniek in Nijmegen, the Netherlands, said in an interview before her presentation of the study during an oral abstract session at the congress. “Stepwise tapering is also better than fixed-dose reduction or discontinuation, since it is much more individualized.”

The study is now published in Annals of the Rheumatic Diseases.

[embed:render:related:node:225445]

In the randomized, controlled, open-label, noninferiority study, researchers enrolled patients with PsA or axSpA who were using a TNF inhibitor such as etanercept, adalimumab, or infliximab, and had stable low disease activity for at least 6 months. Patients needed to have a Psoriatic Arthritis Disease Activity Score (PASDAS) of 3.2 or less, or an Ankylosing Spondylitis Disease Activity Score (ASDAS) of at 2.1 or less. In cases of flare, patients were treated with NSAIDs and/or glucorticoids, and if they still had not reached low disease activity after a month, their previous TNF inhibitor dose was reinstated to the last effective interval or dosage, which was maintained throughout the study period. When the patient was already using a full TNF-inhibitor dose or if dose adjustment did not suffice, patients were switched to another biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD).

Participants were randomized, from January 2019 to June 2021, to a tapering or a nontapering T2T strategy in a 2:1 fashion. Then researchers then followed them for 12 months and aimed to determine if the tapering strategy proved noninferior to not tapering within a predefined 20% margin for noninferiority, which Dr. Michielsens said was derived from other studies and what her group determined to be “an acceptable risk.”

Results show strategy is ‘feasible in daily clinical care’

A total of 81 patients – 42 with PsA and 39 with axSpA – were in the group with tapering, and 41 were in the group without tapering: 22 with PsA and 19 with axSpA.

At 12 months, researchers found that 69% of the patients in the group with tapering had low disease activity, measured via the PASDAS and ASDAS, compared with 73% in patients who did not taper. And those in the tapering group saw their medication use dramatically reduced. At the 12-month mark, they were taking just 53% of the defined daily dose for maintenance, compared with 91% of the defined daily dose for the group that didn’t taper.

The researchers were able to successfully taper 72% of the patients in the tapering group, with 28% of them discontinuing their TNF-inhibitor medication entirely. The incidence of flares was 85% in the tapering group and 78% in the nontapering group, a nonsignificant difference (P = .32).

The start of a new medication or an increase in use of an existing medication was more frequent in the tapering group, and significantly so for NSAIDs. An increase in NSAID use was seen in 54% of the tapering group and in just 24% of the nontapering group (P = .002).

Conventional synthetic DMARD use went up in the tapering group, compared with the nontapering group, but this was only among the PsA patients and the change in use was not statistically significant. There were also more frequent increases in glucocorticoid use in the tapering group, compared with the nontapering group, but this was not significant.

Dr. Michielsens said the findings show the value of an individualized approach in treating patients with PsA or axSpA.

[embed:render:related:node:223732]

“Our study – and those [studies] in rheumatoid arthritis earlier – deliver the highest quality of evidence that disease activity–guided dose personalization can, and in fact should, be used in clinical practice,” she said. “Our pragmatic treat-to-target tapering strategy is feasible in daily clinical care, although treat-to-target using PASDAS and ASDAS needs some implementation. In shared decision-making with patients, a 50% reduction in TNFi use is obtainable, while maintaining low disease activity.”

The increase in the use of NSAIDs is something to be aware of, but it is “not concerning,” Dr. Michielsens added. She pointed out that the NSAID use was typically temporary, used when flares arose, and that the drugs are effective, safe, and inexpensive. She also noted that the use of TNF blockers decreased more than the use of NSAIDs increased.

“This seems a perfectly acceptable trade-off that can be discussed with your patient,” she said.

The 12-month duration of the study is likely long enough to show that the tapering strategy works, Dr. Michielsens said. In rheumatoid arthritis studies, for example, differences in strategies didn’t change after 1 year.

“That said, we are doing an observational extension study to provide more insights in the long-term effects of this treat-to-target strategy,” she said. “At the end of this summer, all patients will have completed their extended follow-up period – a 12-month observational period – so hopefully we can present the results next year at EULAR.”

This study received funding from ReumaNederland. Dr. Michielsens did not have any financial interests to disclose. Two coauthors reported financial relationships with numerous pharmaceutical companies.

Aiming for a disease activity target while reducing biologic therapy could be a winning approach for patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), according to the results of a new study presented at the annual European Congress of Rheumatology.

The findings show that a treat-to-target (T2T) strategy with tapering using a tumor necrosis factor (TNF) inhibitor produces results that are noninferior to a T2T strategy that doesn’t include tapering in these patients.

Michielsens_Celia_NETH_web.jpg

“Our study has for the first time shown that a treat-to-target tapering strategy is just as good as full-dose continuation, while reducing medication use substantially,” first author Celia Michielsens, MD, a PhD student and researcher at Sint Maartenskliniek in Nijmegen, the Netherlands, said in an interview before her presentation of the study during an oral abstract session at the congress. “Stepwise tapering is also better than fixed-dose reduction or discontinuation, since it is much more individualized.”

The study is now published in Annals of the Rheumatic Diseases.

[embed:render:related:node:225445]

In the randomized, controlled, open-label, noninferiority study, researchers enrolled patients with PsA or axSpA who were using a TNF inhibitor such as etanercept, adalimumab, or infliximab, and had stable low disease activity for at least 6 months. Patients needed to have a Psoriatic Arthritis Disease Activity Score (PASDAS) of 3.2 or less, or an Ankylosing Spondylitis Disease Activity Score (ASDAS) of at 2.1 or less. In cases of flare, patients were treated with NSAIDs and/or glucorticoids, and if they still had not reached low disease activity after a month, their previous TNF inhibitor dose was reinstated to the last effective interval or dosage, which was maintained throughout the study period. When the patient was already using a full TNF-inhibitor dose or if dose adjustment did not suffice, patients were switched to another biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD).

Participants were randomized, from January 2019 to June 2021, to a tapering or a nontapering T2T strategy in a 2:1 fashion. Then researchers then followed them for 12 months and aimed to determine if the tapering strategy proved noninferior to not tapering within a predefined 20% margin for noninferiority, which Dr. Michielsens said was derived from other studies and what her group determined to be “an acceptable risk.”

Results show strategy is ‘feasible in daily clinical care’

A total of 81 patients – 42 with PsA and 39 with axSpA – were in the group with tapering, and 41 were in the group without tapering: 22 with PsA and 19 with axSpA.

At 12 months, researchers found that 69% of the patients in the group with tapering had low disease activity, measured via the PASDAS and ASDAS, compared with 73% in patients who did not taper. And those in the tapering group saw their medication use dramatically reduced. At the 12-month mark, they were taking just 53% of the defined daily dose for maintenance, compared with 91% of the defined daily dose for the group that didn’t taper.

The researchers were able to successfully taper 72% of the patients in the tapering group, with 28% of them discontinuing their TNF-inhibitor medication entirely. The incidence of flares was 85% in the tapering group and 78% in the nontapering group, a nonsignificant difference (P = .32).

The start of a new medication or an increase in use of an existing medication was more frequent in the tapering group, and significantly so for NSAIDs. An increase in NSAID use was seen in 54% of the tapering group and in just 24% of the nontapering group (P = .002).

Conventional synthetic DMARD use went up in the tapering group, compared with the nontapering group, but this was only among the PsA patients and the change in use was not statistically significant. There were also more frequent increases in glucocorticoid use in the tapering group, compared with the nontapering group, but this was not significant.

Dr. Michielsens said the findings show the value of an individualized approach in treating patients with PsA or axSpA.

[embed:render:related:node:223732]

“Our study – and those [studies] in rheumatoid arthritis earlier – deliver the highest quality of evidence that disease activity–guided dose personalization can, and in fact should, be used in clinical practice,” she said. “Our pragmatic treat-to-target tapering strategy is feasible in daily clinical care, although treat-to-target using PASDAS and ASDAS needs some implementation. In shared decision-making with patients, a 50% reduction in TNFi use is obtainable, while maintaining low disease activity.”

The increase in the use of NSAIDs is something to be aware of, but it is “not concerning,” Dr. Michielsens added. She pointed out that the NSAID use was typically temporary, used when flares arose, and that the drugs are effective, safe, and inexpensive. She also noted that the use of TNF blockers decreased more than the use of NSAIDs increased.

“This seems a perfectly acceptable trade-off that can be discussed with your patient,” she said.

The 12-month duration of the study is likely long enough to show that the tapering strategy works, Dr. Michielsens said. In rheumatoid arthritis studies, for example, differences in strategies didn’t change after 1 year.

“That said, we are doing an observational extension study to provide more insights in the long-term effects of this treat-to-target strategy,” she said. “At the end of this summer, all patients will have completed their extended follow-up period – a 12-month observational period – so hopefully we can present the results next year at EULAR.”

This study received funding from ReumaNederland. Dr. Michielsens did not have any financial interests to disclose. Two coauthors reported financial relationships with numerous pharmaceutical companies.

Aiming for a disease activity target while reducing biologic therapy could be a winning approach for patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), according to the results of a new study presented at the annual European Congress of Rheumatology.

The findings show that a treat-to-target (T2T) strategy with tapering using a tumor necrosis factor (TNF) inhibitor produces results that are noninferior to a T2T strategy that doesn’t include tapering in these patients.

Michielsens_Celia_NETH_web.jpg

“Our study has for the first time shown that a treat-to-target tapering strategy is just as good as full-dose continuation, while reducing medication use substantially,” first author Celia Michielsens, MD, a PhD student and researcher at Sint Maartenskliniek in Nijmegen, the Netherlands, said in an interview before her presentation of the study during an oral abstract session at the congress. “Stepwise tapering is also better than fixed-dose reduction or discontinuation, since it is much more individualized.”

The study is now published in Annals of the Rheumatic Diseases.

[embed:render:related:node:225445]

In the randomized, controlled, open-label, noninferiority study, researchers enrolled patients with PsA or axSpA who were using a TNF inhibitor such as etanercept, adalimumab, or infliximab, and had stable low disease activity for at least 6 months. Patients needed to have a Psoriatic Arthritis Disease Activity Score (PASDAS) of 3.2 or less, or an Ankylosing Spondylitis Disease Activity Score (ASDAS) of at 2.1 or less. In cases of flare, patients were treated with NSAIDs and/or glucorticoids, and if they still had not reached low disease activity after a month, their previous TNF inhibitor dose was reinstated to the last effective interval or dosage, which was maintained throughout the study period. When the patient was already using a full TNF-inhibitor dose or if dose adjustment did not suffice, patients were switched to another biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD).

Participants were randomized, from January 2019 to June 2021, to a tapering or a nontapering T2T strategy in a 2:1 fashion. Then researchers then followed them for 12 months and aimed to determine if the tapering strategy proved noninferior to not tapering within a predefined 20% margin for noninferiority, which Dr. Michielsens said was derived from other studies and what her group determined to be “an acceptable risk.”

Results show strategy is ‘feasible in daily clinical care’

A total of 81 patients – 42 with PsA and 39 with axSpA – were in the group with tapering, and 41 were in the group without tapering: 22 with PsA and 19 with axSpA.

At 12 months, researchers found that 69% of the patients in the group with tapering had low disease activity, measured via the PASDAS and ASDAS, compared with 73% in patients who did not taper. And those in the tapering group saw their medication use dramatically reduced. At the 12-month mark, they were taking just 53% of the defined daily dose for maintenance, compared with 91% of the defined daily dose for the group that didn’t taper.

The researchers were able to successfully taper 72% of the patients in the tapering group, with 28% of them discontinuing their TNF-inhibitor medication entirely. The incidence of flares was 85% in the tapering group and 78% in the nontapering group, a nonsignificant difference (P = .32).

The start of a new medication or an increase in use of an existing medication was more frequent in the tapering group, and significantly so for NSAIDs. An increase in NSAID use was seen in 54% of the tapering group and in just 24% of the nontapering group (P = .002).

Conventional synthetic DMARD use went up in the tapering group, compared with the nontapering group, but this was only among the PsA patients and the change in use was not statistically significant. There were also more frequent increases in glucocorticoid use in the tapering group, compared with the nontapering group, but this was not significant.

Dr. Michielsens said the findings show the value of an individualized approach in treating patients with PsA or axSpA.

[embed:render:related:node:223732]

“Our study – and those [studies] in rheumatoid arthritis earlier – deliver the highest quality of evidence that disease activity–guided dose personalization can, and in fact should, be used in clinical practice,” she said. “Our pragmatic treat-to-target tapering strategy is feasible in daily clinical care, although treat-to-target using PASDAS and ASDAS needs some implementation. In shared decision-making with patients, a 50% reduction in TNFi use is obtainable, while maintaining low disease activity.”

The increase in the use of NSAIDs is something to be aware of, but it is “not concerning,” Dr. Michielsens added. She pointed out that the NSAID use was typically temporary, used when flares arose, and that the drugs are effective, safe, and inexpensive. She also noted that the use of TNF blockers decreased more than the use of NSAIDs increased.

“This seems a perfectly acceptable trade-off that can be discussed with your patient,” she said.

The 12-month duration of the study is likely long enough to show that the tapering strategy works, Dr. Michielsens said. In rheumatoid arthritis studies, for example, differences in strategies didn’t change after 1 year.

“That said, we are doing an observational extension study to provide more insights in the long-term effects of this treat-to-target strategy,” she said. “At the end of this summer, all patients will have completed their extended follow-up period – a 12-month observational period – so hopefully we can present the results next year at EULAR.”

This study received funding from ReumaNederland. Dr. Michielsens did not have any financial interests to disclose. Two coauthors reported financial relationships with numerous pharmaceutical companies.