Carolyn Crist

Dupilumab appears to improve clinical, symptomatic, histologic, and endoscopic aspects of eosinophilic esophagitis (EoE) up to 24 weeks, according to findings presented at the annual meeting of the American College of Gastroenterology.

The drug was also well tolerated, demonstrating consistency with the known dupilumab safety profile, said Evan S. Dellon, MD, a gastroenterologist at the University of North Carolina at Chapel Hill.

Dellon_Evan_S_NORTH CAROLINA_web.jpg

In May, the Food and Drug Administration approved dupilumab (Dupixent) for the treatment of EoE in adults and adolescents who are 12 years and older and weigh at least 40 kg (about 88 pounds), based on safety and efficacy data previously presented by Dr. Dellon and colleagues as part of the phase 3 LIBERTY-EoE-TREET study (NCT03633617).

“Dupilumab is now the only medication FDA approved to treat EoE in the U.S.,” Dr. Dellon said. “The findings here are that the pooled efficacy and safety data for parts A and B of the phase 3 trial are consistent with the results of the individual parts of the study that were previously reported, and which led to the drug being approved for EoE.”

EoE is a chronic, progressive, type 2 inflammatory disease of the esophagus, which can lead to symptoms of esophageal dysfunction that affect quality of life. Current treatment options often lack specificity, present adherence challenges, and provide suboptimal long-term disease control, Dr. Dellon said.

Dupilumab, a fully human monoclonal antibody manufactured by Regeneron Pharmaceuticals, blocks the shared receptor component for interleukin-4 and IL-13, which are central drivers of type 2 inflammation in EoE.
 

Study population difficult to treat

In the three-part, double-blind, placebo-controlled, phase 3 study, dupilumab was administered to 122 patients as 300-mg weekly doses through subcutaneous injection. In parts A and B, dupilumab demonstrated statistically significant and clinically meaningful improvement in adults and adolescents up to 24 weeks. In patients from part A who continued to an extended active treatment period called part C, efficacy was sustained to week 52.

Participants were included if they had EoE that hadn’t responded to high-dose proton pump inhibitors, had baseline esophageal biopsies with a peak intraepithelial eosinophilic count of 15 eosinophils per high-power field (eos/HPF) or higher in two or more esophageal regions, had a history of an average of two or more episodes of dysphagia per week in the 4 weeks prior to screening, had four or more episodes of dysphagia in the 2 weeks prior to randomization with two or more episodes that required liquids or medical attention, and had a baseline Dysphagia Symptom Questionnaire (DSQ) score of 10 or higher.

On the other hand, participants were excluded if they initiated or changed a food-elimination diet regimen or reintroduced a previously eliminated food group in the 6 weeks before screening, had other causes of esophageal eosinophilia, had a history of other inflammatory diseases such as Crohn’s disease or ulcerative colitis, or were treated with swallowed topical corticosteroids within 8 weeks prior to baseline.

Dr. Dellon and colleagues focused on co–primary endpoints: The proportion of patients who achieved peak esophageal intraepithelial eosinophil count of 6 eos/HPF or less, and the absolute change in DSQ score from baseline to week 24.

Key secondary endpoints included percentage change in eos/HPF, absolute change in EoE-Endoscopic Reference Score (EREFS), absolute change in EoE-Histologic Scoring System (EoE-HSS) grade score, and EoE-HSS stage score. Other secondary endpoints included percentage change in DSQ score and proportion of patients achieving less than 15 eos/HPF.

The baseline demographics and clinical characteristics were similar between the treatment and placebo groups. Importantly, about 70% had been treated with topical corticosteroids, and about 40% had a history of esophageal dilation, Dr. Dellon said. The DSQ scores, peak eosinophil counts, and EREFS scores were high, indicating an inflamed, symptomatic, and difficult-to-treat population.
 

Pooled parts A and B findings

Overall, dupilumab reduced peak esophageal intraepithelial eosinophil counts at week 24. In the dupilumab group, 59% of patients were down to 6 eos/HPF or less, compared with 5.9% in the placebo group. In a secondary endpoint, 77% of dupilumab patients were down to 15 eos/HPF, compared with 7.6% in the placebo group. The dupilumab group saw an 80% drop in baseline change, compared with 1.5% in the placebo group.

Dupilumab also reduced dysphagia symptoms and improved endoscopic features of EoE at week 24. The absolute change in DSQ score was –23.21 in the dupilumab group, compared with –12.69 in the placebo group. The percent change in DSQ score was –65.5% in the dupilumab group, compared with –38.2% in the placebo group. The absolute change in EREFS score was –3.95 in the dupilumab group, compared with –0.41 in the placebo group.

In addition, dupilumab reduced histologic scores at week 24. The absolute change in EoE-HSS grade score was –0.82 in the dupilumab group, compared with –0.1 in the placebo group. The absolute change in EoE-HSS stage score was –0.79 in the dupilumab group, compared with –0.09 in the placebo group.

Dupilumab demonstrated an acceptable safety profile, and no new safety signals were noted, Dr. Dellon said. The most common adverse events was injection-site reaction at 37.5% in the dupilumab group and 33.3% in the placebo group. The severe adverse events were not related to the medication.

“If patients have EoE, dupilumab might be an option for treatment. However, it’s important to realize that, in the phase 3 study, all patients were PPI nonresponders, most had been treated with topical steroids [and many were not responsive], and many had prior esophageal dilation,” Dr. Dellon said. “We don’t have a lot of data in more mild EoE patients, and insurances are currently requiring a series of authorization before patients might be able to get this medication. It’s best to talk to their doctor about whether the medication is a good fit for not.”

The study was sponsored by Sanofi and Regeneron Pharmaceuticals. Three of the authors are employees for and have stock options with Regeneron or Sanofi. The other authors reported consultant roles, advisory roles, and research support from numerous pharmaceutical companies, including Regeneron and Sanofi.

Dupilumab appears to improve clinical, symptomatic, histologic, and endoscopic aspects of eosinophilic esophagitis (EoE) up to 24 weeks, according to findings presented at the annual meeting of the American College of Gastroenterology.

The drug was also well tolerated, demonstrating consistency with the known dupilumab safety profile, said Evan S. Dellon, MD, a gastroenterologist at the University of North Carolina at Chapel Hill.

Dellon_Evan_S_NORTH CAROLINA_web.jpg

In May, the Food and Drug Administration approved dupilumab (Dupixent) for the treatment of EoE in adults and adolescents who are 12 years and older and weigh at least 40 kg (about 88 pounds), based on safety and efficacy data previously presented by Dr. Dellon and colleagues as part of the phase 3 LIBERTY-EoE-TREET study (NCT03633617).

“Dupilumab is now the only medication FDA approved to treat EoE in the U.S.,” Dr. Dellon said. “The findings here are that the pooled efficacy and safety data for parts A and B of the phase 3 trial are consistent with the results of the individual parts of the study that were previously reported, and which led to the drug being approved for EoE.”

EoE is a chronic, progressive, type 2 inflammatory disease of the esophagus, which can lead to symptoms of esophageal dysfunction that affect quality of life. Current treatment options often lack specificity, present adherence challenges, and provide suboptimal long-term disease control, Dr. Dellon said.

Dupilumab, a fully human monoclonal antibody manufactured by Regeneron Pharmaceuticals, blocks the shared receptor component for interleukin-4 and IL-13, which are central drivers of type 2 inflammation in EoE.
 

Study population difficult to treat

In the three-part, double-blind, placebo-controlled, phase 3 study, dupilumab was administered to 122 patients as 300-mg weekly doses through subcutaneous injection. In parts A and B, dupilumab demonstrated statistically significant and clinically meaningful improvement in adults and adolescents up to 24 weeks. In patients from part A who continued to an extended active treatment period called part C, efficacy was sustained to week 52.

Participants were included if they had EoE that hadn’t responded to high-dose proton pump inhibitors, had baseline esophageal biopsies with a peak intraepithelial eosinophilic count of 15 eosinophils per high-power field (eos/HPF) or higher in two or more esophageal regions, had a history of an average of two or more episodes of dysphagia per week in the 4 weeks prior to screening, had four or more episodes of dysphagia in the 2 weeks prior to randomization with two or more episodes that required liquids or medical attention, and had a baseline Dysphagia Symptom Questionnaire (DSQ) score of 10 or higher.

On the other hand, participants were excluded if they initiated or changed a food-elimination diet regimen or reintroduced a previously eliminated food group in the 6 weeks before screening, had other causes of esophageal eosinophilia, had a history of other inflammatory diseases such as Crohn’s disease or ulcerative colitis, or were treated with swallowed topical corticosteroids within 8 weeks prior to baseline.

Dr. Dellon and colleagues focused on co–primary endpoints: The proportion of patients who achieved peak esophageal intraepithelial eosinophil count of 6 eos/HPF or less, and the absolute change in DSQ score from baseline to week 24.

Key secondary endpoints included percentage change in eos/HPF, absolute change in EoE-Endoscopic Reference Score (EREFS), absolute change in EoE-Histologic Scoring System (EoE-HSS) grade score, and EoE-HSS stage score. Other secondary endpoints included percentage change in DSQ score and proportion of patients achieving less than 15 eos/HPF.

The baseline demographics and clinical characteristics were similar between the treatment and placebo groups. Importantly, about 70% had been treated with topical corticosteroids, and about 40% had a history of esophageal dilation, Dr. Dellon said. The DSQ scores, peak eosinophil counts, and EREFS scores were high, indicating an inflamed, symptomatic, and difficult-to-treat population.
 

Pooled parts A and B findings

Overall, dupilumab reduced peak esophageal intraepithelial eosinophil counts at week 24. In the dupilumab group, 59% of patients were down to 6 eos/HPF or less, compared with 5.9% in the placebo group. In a secondary endpoint, 77% of dupilumab patients were down to 15 eos/HPF, compared with 7.6% in the placebo group. The dupilumab group saw an 80% drop in baseline change, compared with 1.5% in the placebo group.

Dupilumab also reduced dysphagia symptoms and improved endoscopic features of EoE at week 24. The absolute change in DSQ score was –23.21 in the dupilumab group, compared with –12.69 in the placebo group. The percent change in DSQ score was –65.5% in the dupilumab group, compared with –38.2% in the placebo group. The absolute change in EREFS score was –3.95 in the dupilumab group, compared with –0.41 in the placebo group.

In addition, dupilumab reduced histologic scores at week 24. The absolute change in EoE-HSS grade score was –0.82 in the dupilumab group, compared with –0.1 in the placebo group. The absolute change in EoE-HSS stage score was –0.79 in the dupilumab group, compared with –0.09 in the placebo group.

Dupilumab demonstrated an acceptable safety profile, and no new safety signals were noted, Dr. Dellon said. The most common adverse events was injection-site reaction at 37.5% in the dupilumab group and 33.3% in the placebo group. The severe adverse events were not related to the medication.

“If patients have EoE, dupilumab might be an option for treatment. However, it’s important to realize that, in the phase 3 study, all patients were PPI nonresponders, most had been treated with topical steroids [and many were not responsive], and many had prior esophageal dilation,” Dr. Dellon said. “We don’t have a lot of data in more mild EoE patients, and insurances are currently requiring a series of authorization before patients might be able to get this medication. It’s best to talk to their doctor about whether the medication is a good fit for not.”

The study was sponsored by Sanofi and Regeneron Pharmaceuticals. Three of the authors are employees for and have stock options with Regeneron or Sanofi. The other authors reported consultant roles, advisory roles, and research support from numerous pharmaceutical companies, including Regeneron and Sanofi.

Dupilumab appears to improve clinical, symptomatic, histologic, and endoscopic aspects of eosinophilic esophagitis (EoE) up to 24 weeks, according to findings presented at the annual meeting of the American College of Gastroenterology.

The drug was also well tolerated, demonstrating consistency with the known dupilumab safety profile, said Evan S. Dellon, MD, a gastroenterologist at the University of North Carolina at Chapel Hill.

Dellon_Evan_S_NORTH CAROLINA_web.jpg

In May, the Food and Drug Administration approved dupilumab (Dupixent) for the treatment of EoE in adults and adolescents who are 12 years and older and weigh at least 40 kg (about 88 pounds), based on safety and efficacy data previously presented by Dr. Dellon and colleagues as part of the phase 3 LIBERTY-EoE-TREET study (NCT03633617).

“Dupilumab is now the only medication FDA approved to treat EoE in the U.S.,” Dr. Dellon said. “The findings here are that the pooled efficacy and safety data for parts A and B of the phase 3 trial are consistent with the results of the individual parts of the study that were previously reported, and which led to the drug being approved for EoE.”

EoE is a chronic, progressive, type 2 inflammatory disease of the esophagus, which can lead to symptoms of esophageal dysfunction that affect quality of life. Current treatment options often lack specificity, present adherence challenges, and provide suboptimal long-term disease control, Dr. Dellon said.

Dupilumab, a fully human monoclonal antibody manufactured by Regeneron Pharmaceuticals, blocks the shared receptor component for interleukin-4 and IL-13, which are central drivers of type 2 inflammation in EoE.
 

Study population difficult to treat

In the three-part, double-blind, placebo-controlled, phase 3 study, dupilumab was administered to 122 patients as 300-mg weekly doses through subcutaneous injection. In parts A and B, dupilumab demonstrated statistically significant and clinically meaningful improvement in adults and adolescents up to 24 weeks. In patients from part A who continued to an extended active treatment period called part C, efficacy was sustained to week 52.

Participants were included if they had EoE that hadn’t responded to high-dose proton pump inhibitors, had baseline esophageal biopsies with a peak intraepithelial eosinophilic count of 15 eosinophils per high-power field (eos/HPF) or higher in two or more esophageal regions, had a history of an average of two or more episodes of dysphagia per week in the 4 weeks prior to screening, had four or more episodes of dysphagia in the 2 weeks prior to randomization with two or more episodes that required liquids or medical attention, and had a baseline Dysphagia Symptom Questionnaire (DSQ) score of 10 or higher.

On the other hand, participants were excluded if they initiated or changed a food-elimination diet regimen or reintroduced a previously eliminated food group in the 6 weeks before screening, had other causes of esophageal eosinophilia, had a history of other inflammatory diseases such as Crohn’s disease or ulcerative colitis, or were treated with swallowed topical corticosteroids within 8 weeks prior to baseline.

Dr. Dellon and colleagues focused on co–primary endpoints: The proportion of patients who achieved peak esophageal intraepithelial eosinophil count of 6 eos/HPF or less, and the absolute change in DSQ score from baseline to week 24.

Key secondary endpoints included percentage change in eos/HPF, absolute change in EoE-Endoscopic Reference Score (EREFS), absolute change in EoE-Histologic Scoring System (EoE-HSS) grade score, and EoE-HSS stage score. Other secondary endpoints included percentage change in DSQ score and proportion of patients achieving less than 15 eos/HPF.

The baseline demographics and clinical characteristics were similar between the treatment and placebo groups. Importantly, about 70% had been treated with topical corticosteroids, and about 40% had a history of esophageal dilation, Dr. Dellon said. The DSQ scores, peak eosinophil counts, and EREFS scores were high, indicating an inflamed, symptomatic, and difficult-to-treat population.
 

Pooled parts A and B findings

Overall, dupilumab reduced peak esophageal intraepithelial eosinophil counts at week 24. In the dupilumab group, 59% of patients were down to 6 eos/HPF or less, compared with 5.9% in the placebo group. In a secondary endpoint, 77% of dupilumab patients were down to 15 eos/HPF, compared with 7.6% in the placebo group. The dupilumab group saw an 80% drop in baseline change, compared with 1.5% in the placebo group.

Dupilumab also reduced dysphagia symptoms and improved endoscopic features of EoE at week 24. The absolute change in DSQ score was –23.21 in the dupilumab group, compared with –12.69 in the placebo group. The percent change in DSQ score was –65.5% in the dupilumab group, compared with –38.2% in the placebo group. The absolute change in EREFS score was –3.95 in the dupilumab group, compared with –0.41 in the placebo group.

In addition, dupilumab reduced histologic scores at week 24. The absolute change in EoE-HSS grade score was –0.82 in the dupilumab group, compared with –0.1 in the placebo group. The absolute change in EoE-HSS stage score was –0.79 in the dupilumab group, compared with –0.09 in the placebo group.

Dupilumab demonstrated an acceptable safety profile, and no new safety signals were noted, Dr. Dellon said. The most common adverse events was injection-site reaction at 37.5% in the dupilumab group and 33.3% in the placebo group. The severe adverse events were not related to the medication.

“If patients have EoE, dupilumab might be an option for treatment. However, it’s important to realize that, in the phase 3 study, all patients were PPI nonresponders, most had been treated with topical steroids [and many were not responsive], and many had prior esophageal dilation,” Dr. Dellon said. “We don’t have a lot of data in more mild EoE patients, and insurances are currently requiring a series of authorization before patients might be able to get this medication. It’s best to talk to their doctor about whether the medication is a good fit for not.”

The study was sponsored by Sanofi and Regeneron Pharmaceuticals. Three of the authors are employees for and have stock options with Regeneron or Sanofi. The other authors reported consultant roles, advisory roles, and research support from numerous pharmaceutical companies, including Regeneron and Sanofi.

Four major professional medical societies in the United States have called for urgent action to create a more sustainable model for digestive health care that decreases the environmental impact of gastroenterology practice, according to a new joint strategic plan published simultaneously in Gastroenterology, Gastrointestinal Endoscopy, American Journal of Gastroenterology, and Hepatology.

The plan outlines numerous strategic goals and objectives across clinical care, education, research, and industry to support sustainable practices. With first author Heiko Pohl, MD, a gastroenterologist and hepatologist at the Veterans Affairs Medical Center in White River Junction, Vermont, and professor of medicine at the Geisel School of Medicine at Dartmouth, Hanover, N.H., the joint statement includes task force members from the American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy.

Pohl_Heiko_VT_web.png

“It is clear that the evolving climate crisis, with its deleterious effects on planetary ecosystems, also poses harm to the health of humankind,” the authors wrote in Gastroenterology.

“Climate change affects many social and environmental determinants of health, including water and food security, shelter, physical activity, and accessible health care,” they added. These changes influence gastrointestinal practice (for example, increased risk of obesity and fatty liver disease, disruption of the microbiome, compromised gut immune function).

At the same time, health care delivery contributes to climate change and greenhouse gas emissions worldwide, they wrote. As a procedure-intensive specialty, digestive health care adds to the health care carbon footprint through single-use supplies and high levels of waste.

“As is the case for the impact of climate change by and on health care systems, there is a vicious cycle whereby climate change negatively impacts individual digestive health, which accelerates specialized health care activity, which further contributes to the climate crisis,” the authors wrote.

The multisociety task force noted the transition to a more sustainable model will be challenging and require major modification of current habits in practice. However, the long-term effects “will promote health, save cost, and ... correspond with a broader shared vision of planetary health,” they wrote.

The strategic plan covers seven domains: clinical settings, education, research, society efforts, intersociety efforts, industry, and advocacy. Each domain has specific initiatives for 2023 to 2027. Years 1 and 2 are conceived as a period of self-assessment and planning, followed by implementation and assessment during years 3-5.

In the plan, clinical settings would assess the carbon footprint and waste within all areas of practice and identify low-carbon and low-waste alternatives, such as immediate, short-term, and long-term solutions. This involves creating a framework for GI practices to develop sustainability metrics and offer affordable testing and treatment alternatives with a favorable environmental impact.

Through education, the societies would raise awareness and share sustainability practices with health care leadership, practitioners, and patients regarding the interactions among climate change, digestive health, and health care services. This would include discussions about the professional and ethical implications of old and new patterns of shared resource utilization.

The societies also support raising and allocating resources for research related to the intersections of climate change, digestive health, and health care, with an emphasis on vulnerable groups. This would encourage the inclusion of environmental considerations in research proposals.

At the GI society level, the groups suggest assessing and monitoring the current environmental impact of society-related activities. This entails identifying and implementing measures that would decrease the carbon footprint and reduce waste, as well as track financial costs and savings and environmental benefits from efforts included in a sustainability model.

At the intersociety level, the U.S. groups would collaborate with national and international GI and hepatology societies to support sustainability efforts and use validated metrics to evaluate their efforts. The multisociety plan has received endorsements from nearly two-dozen groups, including the Crohn’s & Colitis Foundation, World Endoscopy Organization, and World Gastroenterology Organisation.

The plan calls for engagement with GI- and hepatology-focused industry and pharmaceutical partners to develop environmentally friendly products, publish information on carbon footprint implications, and promote options for recycling.

Through advocacy efforts, the societies would also identify and incorporate principles of sustainable health care among the goals of relevant political action committees, as well as leverage collaborative advocacy efforts with national and international health care and research agencies, political leaders, and payors.

“We are grateful that several other GI organizations have endorsed our plan, which reflects the importance and timeliness of the opportunity to work together and share best practices to overcome the burden of climate change on digestive health and help mitigate the environmental impact of GI practice,” the authors concluded.

The authors did not declare a funding source for the report. Several of the authors declared financial relationships with pharmaceutical companies, serving as a consultant or receiving research funding.

Four major professional medical societies in the United States have called for urgent action to create a more sustainable model for digestive health care that decreases the environmental impact of gastroenterology practice, according to a new joint strategic plan published simultaneously in Gastroenterology, Gastrointestinal Endoscopy, American Journal of Gastroenterology, and Hepatology.

The plan outlines numerous strategic goals and objectives across clinical care, education, research, and industry to support sustainable practices. With first author Heiko Pohl, MD, a gastroenterologist and hepatologist at the Veterans Affairs Medical Center in White River Junction, Vermont, and professor of medicine at the Geisel School of Medicine at Dartmouth, Hanover, N.H., the joint statement includes task force members from the American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy.

Pohl_Heiko_VT_web.png

“It is clear that the evolving climate crisis, with its deleterious effects on planetary ecosystems, also poses harm to the health of humankind,” the authors wrote in Gastroenterology.

“Climate change affects many social and environmental determinants of health, including water and food security, shelter, physical activity, and accessible health care,” they added. These changes influence gastrointestinal practice (for example, increased risk of obesity and fatty liver disease, disruption of the microbiome, compromised gut immune function).

At the same time, health care delivery contributes to climate change and greenhouse gas emissions worldwide, they wrote. As a procedure-intensive specialty, digestive health care adds to the health care carbon footprint through single-use supplies and high levels of waste.

“As is the case for the impact of climate change by and on health care systems, there is a vicious cycle whereby climate change negatively impacts individual digestive health, which accelerates specialized health care activity, which further contributes to the climate crisis,” the authors wrote.

The multisociety task force noted the transition to a more sustainable model will be challenging and require major modification of current habits in practice. However, the long-term effects “will promote health, save cost, and ... correspond with a broader shared vision of planetary health,” they wrote.

The strategic plan covers seven domains: clinical settings, education, research, society efforts, intersociety efforts, industry, and advocacy. Each domain has specific initiatives for 2023 to 2027. Years 1 and 2 are conceived as a period of self-assessment and planning, followed by implementation and assessment during years 3-5.

In the plan, clinical settings would assess the carbon footprint and waste within all areas of practice and identify low-carbon and low-waste alternatives, such as immediate, short-term, and long-term solutions. This involves creating a framework for GI practices to develop sustainability metrics and offer affordable testing and treatment alternatives with a favorable environmental impact.

Through education, the societies would raise awareness and share sustainability practices with health care leadership, practitioners, and patients regarding the interactions among climate change, digestive health, and health care services. This would include discussions about the professional and ethical implications of old and new patterns of shared resource utilization.

The societies also support raising and allocating resources for research related to the intersections of climate change, digestive health, and health care, with an emphasis on vulnerable groups. This would encourage the inclusion of environmental considerations in research proposals.

At the GI society level, the groups suggest assessing and monitoring the current environmental impact of society-related activities. This entails identifying and implementing measures that would decrease the carbon footprint and reduce waste, as well as track financial costs and savings and environmental benefits from efforts included in a sustainability model.

At the intersociety level, the U.S. groups would collaborate with national and international GI and hepatology societies to support sustainability efforts and use validated metrics to evaluate their efforts. The multisociety plan has received endorsements from nearly two-dozen groups, including the Crohn’s & Colitis Foundation, World Endoscopy Organization, and World Gastroenterology Organisation.

The plan calls for engagement with GI- and hepatology-focused industry and pharmaceutical partners to develop environmentally friendly products, publish information on carbon footprint implications, and promote options for recycling.

Through advocacy efforts, the societies would also identify and incorporate principles of sustainable health care among the goals of relevant political action committees, as well as leverage collaborative advocacy efforts with national and international health care and research agencies, political leaders, and payors.

“We are grateful that several other GI organizations have endorsed our plan, which reflects the importance and timeliness of the opportunity to work together and share best practices to overcome the burden of climate change on digestive health and help mitigate the environmental impact of GI practice,” the authors concluded.

The authors did not declare a funding source for the report. Several of the authors declared financial relationships with pharmaceutical companies, serving as a consultant or receiving research funding.

Four major professional medical societies in the United States have called for urgent action to create a more sustainable model for digestive health care that decreases the environmental impact of gastroenterology practice, according to a new joint strategic plan published simultaneously in Gastroenterology, Gastrointestinal Endoscopy, American Journal of Gastroenterology, and Hepatology.

The plan outlines numerous strategic goals and objectives across clinical care, education, research, and industry to support sustainable practices. With first author Heiko Pohl, MD, a gastroenterologist and hepatologist at the Veterans Affairs Medical Center in White River Junction, Vermont, and professor of medicine at the Geisel School of Medicine at Dartmouth, Hanover, N.H., the joint statement includes task force members from the American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy.

Pohl_Heiko_VT_web.png

“It is clear that the evolving climate crisis, with its deleterious effects on planetary ecosystems, also poses harm to the health of humankind,” the authors wrote in Gastroenterology.

“Climate change affects many social and environmental determinants of health, including water and food security, shelter, physical activity, and accessible health care,” they added. These changes influence gastrointestinal practice (for example, increased risk of obesity and fatty liver disease, disruption of the microbiome, compromised gut immune function).

At the same time, health care delivery contributes to climate change and greenhouse gas emissions worldwide, they wrote. As a procedure-intensive specialty, digestive health care adds to the health care carbon footprint through single-use supplies and high levels of waste.

“As is the case for the impact of climate change by and on health care systems, there is a vicious cycle whereby climate change negatively impacts individual digestive health, which accelerates specialized health care activity, which further contributes to the climate crisis,” the authors wrote.

The multisociety task force noted the transition to a more sustainable model will be challenging and require major modification of current habits in practice. However, the long-term effects “will promote health, save cost, and ... correspond with a broader shared vision of planetary health,” they wrote.

The strategic plan covers seven domains: clinical settings, education, research, society efforts, intersociety efforts, industry, and advocacy. Each domain has specific initiatives for 2023 to 2027. Years 1 and 2 are conceived as a period of self-assessment and planning, followed by implementation and assessment during years 3-5.

In the plan, clinical settings would assess the carbon footprint and waste within all areas of practice and identify low-carbon and low-waste alternatives, such as immediate, short-term, and long-term solutions. This involves creating a framework for GI practices to develop sustainability metrics and offer affordable testing and treatment alternatives with a favorable environmental impact.

Through education, the societies would raise awareness and share sustainability practices with health care leadership, practitioners, and patients regarding the interactions among climate change, digestive health, and health care services. This would include discussions about the professional and ethical implications of old and new patterns of shared resource utilization.

The societies also support raising and allocating resources for research related to the intersections of climate change, digestive health, and health care, with an emphasis on vulnerable groups. This would encourage the inclusion of environmental considerations in research proposals.

At the GI society level, the groups suggest assessing and monitoring the current environmental impact of society-related activities. This entails identifying and implementing measures that would decrease the carbon footprint and reduce waste, as well as track financial costs and savings and environmental benefits from efforts included in a sustainability model.

At the intersociety level, the U.S. groups would collaborate with national and international GI and hepatology societies to support sustainability efforts and use validated metrics to evaluate their efforts. The multisociety plan has received endorsements from nearly two-dozen groups, including the Crohn’s & Colitis Foundation, World Endoscopy Organization, and World Gastroenterology Organisation.

The plan calls for engagement with GI- and hepatology-focused industry and pharmaceutical partners to develop environmentally friendly products, publish information on carbon footprint implications, and promote options for recycling.

Through advocacy efforts, the societies would also identify and incorporate principles of sustainable health care among the goals of relevant political action committees, as well as leverage collaborative advocacy efforts with national and international health care and research agencies, political leaders, and payors.

“We are grateful that several other GI organizations have endorsed our plan, which reflects the importance and timeliness of the opportunity to work together and share best practices to overcome the burden of climate change on digestive health and help mitigate the environmental impact of GI practice,” the authors concluded.

The authors did not declare a funding source for the report. Several of the authors declared financial relationships with pharmaceutical companies, serving as a consultant or receiving research funding.

In a gluten challenge trial, latiglutenase (IMGX003) reduced symptom severity and mucosal deterioration in patients with celiac disease, according to a new study published in Gastroenterology.

Latiglutenase led to 95% gluten degradation in the stomach, as indicated by measurements of gluten-immunogenic peptides in urine, wrote Joseph A. Murray, MD, a gastroenterologist at the Mayo Clinic, Rochester, Minn., and Jack A. Syage, PhD, CEO and cofounder of ImmunogenX Inc., Newport Beach, Calif., and colleagues on behalf of the CeliacShield Study Group.

Murray_Joseph_MINN_2022_web.jpg

For patients with celiac disease, the only available treatment is a life-long gluten-free diet (GFD). Low levels of gluten exposure can lead to ongoing inflammation and the risk of complications, and about half of patients continue to experience moderate to severe symptoms.

“Although a GFD can reduce symptoms and intestinal damage, the diet is neither easy nor readily achievable by many patients and, furthermore, can be lacking in essential nutrients,” the authors wrote.

In a randomized, double-blind, placebo-controlled gluten challenge study, the research team assessed the efficacy and safety of a 1,200-mg dose of IMGX003, formerly known as ALV003. The dual-enzyme supplementation therapy was “designed to mitigate the impact of gluten exposure in patients who are attempting to adhere to a GFD.”

The phase 2 trial was conducted at the Mayo Clinic with adult patients (aged 18-80 years) who had physician-diagnosed and biopsy-confirmed celiac disease, followed a GFD for more than 1 year, and had histologically well-controlled disease. During the study, they were exposed to 2 g of gluten per day for 6 weeks.

Syage_Jack_CALIF_web.jpg

The primary endpoint focused on the change in the ratio of villus height to crypt depth. The “secondary endpoints included density of intraepithelial lymphocytes and symptom severity. Additional endpoints included serology and gluten-immunogenic peptides in urine.”

Among the 50 patients randomized, 43 completed the study, with 21 assigned to the IMGX003 group. About 74% of the participants were women; the mean age of all participants was 43.8 years.

Overall, the mean change in the ratio of villus height to crypt depth was –0.04 for IMGX003, compared with –0.35 for placebo. In addition, the mean change in the density of intraepithelial lymphocytes for IMGX003 was 9.8, compared with 24.8 for placebo. Based on the ratio of the means for both groups, the researchers estimated an 88% reduction of change in villus height to crypt depth and a 60% reduction of change in intraepithelial lymphocytes.

The mean changes, or worsening from baseline, in symptom severity for IMGX003 vs. placebo were 0.22 vs. 1.63 for abdominal pain, 0.96 vs. 3.29 for bloating, 0.02 vs. 3.2 for tiredness, and 0.64 vs. 2.27 for nonstool composite. The calculated symptom reduction values were 93% for abdominal pain, 53% for bloating, 99% for tiredness, and 70% for nonstool composite.

The mean change from baseline for symptom severity was evaluated over three 2-week periods, and the percent changes showed consistent reduction of symptom worsening during that time. Based on the effect size and trend significance, the P values were .014 for abdominal pain, .030 for bloating, .002 for tiredness, and < . 001 for nonstool composite.

The mean change in gluten-immunogenic peptides in urine (GIP) relative to baseline was 0.59 for IMGX003, compared with 11.53 for placebo. The researchers estimated an efficacy of gluten degradation in vivo of 95%.

“Measurement of GIP in urine demonstrated the purported mechanism of action of IMGX003, namely, degradation of gluten in the stomach, thereby preventing the triggering of the immunogenic autoimmune response,” the authors wrote. “Targeting gluten by degrading the immunogenic peptides before absorption minimizes or abrogates the cascading innate and adaptive immune responses that characterize the inflammatory response to gluten in CeD [celiac disease].”

The study was sponsored by ImmunogenX Inc., and partially funded by a grant from the National Center for Complementary and Integrative Health. The project was further supported by grants from the National Center for Advancing Translational Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases. Several authors reported receiving grants from numerous funders, including ImmunogenX, and some reported being a cofounder, stockholder, or board director of the company.

In a gluten challenge trial, latiglutenase (IMGX003) reduced symptom severity and mucosal deterioration in patients with celiac disease, according to a new study published in Gastroenterology.

Latiglutenase led to 95% gluten degradation in the stomach, as indicated by measurements of gluten-immunogenic peptides in urine, wrote Joseph A. Murray, MD, a gastroenterologist at the Mayo Clinic, Rochester, Minn., and Jack A. Syage, PhD, CEO and cofounder of ImmunogenX Inc., Newport Beach, Calif., and colleagues on behalf of the CeliacShield Study Group.

Murray_Joseph_MINN_2022_web.jpg

For patients with celiac disease, the only available treatment is a life-long gluten-free diet (GFD). Low levels of gluten exposure can lead to ongoing inflammation and the risk of complications, and about half of patients continue to experience moderate to severe symptoms.

“Although a GFD can reduce symptoms and intestinal damage, the diet is neither easy nor readily achievable by many patients and, furthermore, can be lacking in essential nutrients,” the authors wrote.

In a randomized, double-blind, placebo-controlled gluten challenge study, the research team assessed the efficacy and safety of a 1,200-mg dose of IMGX003, formerly known as ALV003. The dual-enzyme supplementation therapy was “designed to mitigate the impact of gluten exposure in patients who are attempting to adhere to a GFD.”

The phase 2 trial was conducted at the Mayo Clinic with adult patients (aged 18-80 years) who had physician-diagnosed and biopsy-confirmed celiac disease, followed a GFD for more than 1 year, and had histologically well-controlled disease. During the study, they were exposed to 2 g of gluten per day for 6 weeks.

Syage_Jack_CALIF_web.jpg

The primary endpoint focused on the change in the ratio of villus height to crypt depth. The “secondary endpoints included density of intraepithelial lymphocytes and symptom severity. Additional endpoints included serology and gluten-immunogenic peptides in urine.”

Among the 50 patients randomized, 43 completed the study, with 21 assigned to the IMGX003 group. About 74% of the participants were women; the mean age of all participants was 43.8 years.

Overall, the mean change in the ratio of villus height to crypt depth was –0.04 for IMGX003, compared with –0.35 for placebo. In addition, the mean change in the density of intraepithelial lymphocytes for IMGX003 was 9.8, compared with 24.8 for placebo. Based on the ratio of the means for both groups, the researchers estimated an 88% reduction of change in villus height to crypt depth and a 60% reduction of change in intraepithelial lymphocytes.

The mean changes, or worsening from baseline, in symptom severity for IMGX003 vs. placebo were 0.22 vs. 1.63 for abdominal pain, 0.96 vs. 3.29 for bloating, 0.02 vs. 3.2 for tiredness, and 0.64 vs. 2.27 for nonstool composite. The calculated symptom reduction values were 93% for abdominal pain, 53% for bloating, 99% for tiredness, and 70% for nonstool composite.

The mean change from baseline for symptom severity was evaluated over three 2-week periods, and the percent changes showed consistent reduction of symptom worsening during that time. Based on the effect size and trend significance, the P values were .014 for abdominal pain, .030 for bloating, .002 for tiredness, and < . 001 for nonstool composite.

The mean change in gluten-immunogenic peptides in urine (GIP) relative to baseline was 0.59 for IMGX003, compared with 11.53 for placebo. The researchers estimated an efficacy of gluten degradation in vivo of 95%.

“Measurement of GIP in urine demonstrated the purported mechanism of action of IMGX003, namely, degradation of gluten in the stomach, thereby preventing the triggering of the immunogenic autoimmune response,” the authors wrote. “Targeting gluten by degrading the immunogenic peptides before absorption minimizes or abrogates the cascading innate and adaptive immune responses that characterize the inflammatory response to gluten in CeD [celiac disease].”

The study was sponsored by ImmunogenX Inc., and partially funded by a grant from the National Center for Complementary and Integrative Health. The project was further supported by grants from the National Center for Advancing Translational Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases. Several authors reported receiving grants from numerous funders, including ImmunogenX, and some reported being a cofounder, stockholder, or board director of the company.

In a gluten challenge trial, latiglutenase (IMGX003) reduced symptom severity and mucosal deterioration in patients with celiac disease, according to a new study published in Gastroenterology.

Latiglutenase led to 95% gluten degradation in the stomach, as indicated by measurements of gluten-immunogenic peptides in urine, wrote Joseph A. Murray, MD, a gastroenterologist at the Mayo Clinic, Rochester, Minn., and Jack A. Syage, PhD, CEO and cofounder of ImmunogenX Inc., Newport Beach, Calif., and colleagues on behalf of the CeliacShield Study Group.

Murray_Joseph_MINN_2022_web.jpg

For patients with celiac disease, the only available treatment is a life-long gluten-free diet (GFD). Low levels of gluten exposure can lead to ongoing inflammation and the risk of complications, and about half of patients continue to experience moderate to severe symptoms.

“Although a GFD can reduce symptoms and intestinal damage, the diet is neither easy nor readily achievable by many patients and, furthermore, can be lacking in essential nutrients,” the authors wrote.

In a randomized, double-blind, placebo-controlled gluten challenge study, the research team assessed the efficacy and safety of a 1,200-mg dose of IMGX003, formerly known as ALV003. The dual-enzyme supplementation therapy was “designed to mitigate the impact of gluten exposure in patients who are attempting to adhere to a GFD.”

The phase 2 trial was conducted at the Mayo Clinic with adult patients (aged 18-80 years) who had physician-diagnosed and biopsy-confirmed celiac disease, followed a GFD for more than 1 year, and had histologically well-controlled disease. During the study, they were exposed to 2 g of gluten per day for 6 weeks.

Syage_Jack_CALIF_web.jpg

The primary endpoint focused on the change in the ratio of villus height to crypt depth. The “secondary endpoints included density of intraepithelial lymphocytes and symptom severity. Additional endpoints included serology and gluten-immunogenic peptides in urine.”

Among the 50 patients randomized, 43 completed the study, with 21 assigned to the IMGX003 group. About 74% of the participants were women; the mean age of all participants was 43.8 years.

Overall, the mean change in the ratio of villus height to crypt depth was –0.04 for IMGX003, compared with –0.35 for placebo. In addition, the mean change in the density of intraepithelial lymphocytes for IMGX003 was 9.8, compared with 24.8 for placebo. Based on the ratio of the means for both groups, the researchers estimated an 88% reduction of change in villus height to crypt depth and a 60% reduction of change in intraepithelial lymphocytes.

The mean changes, or worsening from baseline, in symptom severity for IMGX003 vs. placebo were 0.22 vs. 1.63 for abdominal pain, 0.96 vs. 3.29 for bloating, 0.02 vs. 3.2 for tiredness, and 0.64 vs. 2.27 for nonstool composite. The calculated symptom reduction values were 93% for abdominal pain, 53% for bloating, 99% for tiredness, and 70% for nonstool composite.

The mean change from baseline for symptom severity was evaluated over three 2-week periods, and the percent changes showed consistent reduction of symptom worsening during that time. Based on the effect size and trend significance, the P values were .014 for abdominal pain, .030 for bloating, .002 for tiredness, and < . 001 for nonstool composite.

The mean change in gluten-immunogenic peptides in urine (GIP) relative to baseline was 0.59 for IMGX003, compared with 11.53 for placebo. The researchers estimated an efficacy of gluten degradation in vivo of 95%.

“Measurement of GIP in urine demonstrated the purported mechanism of action of IMGX003, namely, degradation of gluten in the stomach, thereby preventing the triggering of the immunogenic autoimmune response,” the authors wrote. “Targeting gluten by degrading the immunogenic peptides before absorption minimizes or abrogates the cascading innate and adaptive immune responses that characterize the inflammatory response to gluten in CeD [celiac disease].”

The study was sponsored by ImmunogenX Inc., and partially funded by a grant from the National Center for Complementary and Integrative Health. The project was further supported by grants from the National Center for Advancing Translational Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases. Several authors reported receiving grants from numerous funders, including ImmunogenX, and some reported being a cofounder, stockholder, or board director of the company.

In a subgroup of patients with hepatorenal syndrome type 1 (HRS) who received a liver transplant, terlipressin treatment appears to reduce the need for renal replacement therapy (RRT) through 12 months of follow-up, according to a study presented at the annual meeting of the American College of Gastroenterology.

Among transplant recipients, overall 12-month survival was 11% higher for those treated with terlipressin compared with placebo, said K. Rajender Reddy, MD, director of hepatology and medical director of liver transplantation at the University of Pennsylvania, Philadelphia.

“Hepatorenal syndrome type 1 is a potentially reversible form of acute kidney injury that occurs in the setting of end-stage liver disease,” he said.

Liver transplantation, which eliminates end-stage liver disease, is the only definitive treatment for HRS. However, renal replacement therapy is common and associated with poor clinical outcomes and low patient survival rates in both the pretransplant and posttransplant settings, he noted.

Terlipressin, an injectable synthetic vasopressin analogue, restores renal blood flow and reverses HRS in 20%-40% of patients, Dr. Reddy said. In September, the U.S. Food and Drug Administration approved terlipressin (Terlivaz) for patients with HRS type 1. The label has a boxed warning for serious or fatal respiratory failure.

The safety and efficacy were assessed in the phase 3 CONFIRM trial, which Dr. Reddy and colleagues previously published. The randomized, placebo-controlled study demonstrated that terlipressin reversed HRS and reduced the need for RRT through day 30. The reversal of HRS with terlipressin did not improve 90-day survival as compared with placebo, which researchers attributed to a higher death rate within 90 days after the first dose despite improved kidney function.

A closer look at the liver transplant patients

In the subgroup analysis of the CONFIRM study, Dr. Reddy and colleagues analyzed the clinical outcomes through 12 months of follow-up in patients with HRS who received a liver transplant. They looked at the incidence of verified HRS reversal, HRS reversal, need for RRT, and overall survival.

Verified HRS reversal was defined as two consecutive serum creatinine measurements of 1.5 mg/dL or less at least 2 hours apart up to day 14 and survival without RRT for at least 10 days. HRS reversal was defined as a serum creatinine level of 1.5 mg/dL or less while on treatment. In addition, the need for RRT and overall survival were assessed at days 30, 60, 90, 180, and 365.

RRT was defined as any procedure that replaced nonendocrine kidney function, including continuous hemofiltration and hemodialysis, intermittent hemodialysis, peritoneal dialysis, ultrafiltration, or other dialysis and filtration techniques.

In the CONFIRM study, 199 patients with HRS were treated with terlipressin plus albumin, and 101 patients were treated with placebo plus albumin for up to 14 days. In the terlipressin group, 46 patients received liver transplants within the first 2 months of the study, as did 29 in the placebo group. Two patients in the terlipressin group and one in the placebo group received a simultaneous liver-kidney transplant.
 

Meaningful clinical outcomes

In the 12-month follow-up subgroup analysis, verified HRS reversal was statistically comparable between the groups, with a 30% decrease in the terlipressin group and 17% decrease in the placebo group, Dr. Reddy reported.

HRS reversal was higher in the terlipressin group, at 37%, as compared with 14% in the placebo group.

The pretransplant need for RRT was lower in the terlipressin group, at 30%, as compared with 62% in the placebo group. The posttransplant need for RRT remained numerically lower in the terlipressin group at all time points and was significantly lower at day 180 and day 365.

Overall survival for transplant recipients in the terlipressin group was 94%, as compared with 83% in the placebo group. Posttreatment adverse events and severe adverse events were similar between the groups.

“Collectively, these data indicate that terlipressin treatment in patients with HRS led to better long-term clinical outcomes in those who received a liver transplant,” Dr. Reddy said.

The study was funded by Mallinckrodt Pharmaceuticals, which manufactures terlipressin. One author is an employee of Mallinckrodt, and the other authors have served in an advisory role or received grant support from Mallinckrodt. The authors also disclosed consultant roles and research support from several other pharmaceutical companies.

In a subgroup of patients with hepatorenal syndrome type 1 (HRS) who received a liver transplant, terlipressin treatment appears to reduce the need for renal replacement therapy (RRT) through 12 months of follow-up, according to a study presented at the annual meeting of the American College of Gastroenterology.

Among transplant recipients, overall 12-month survival was 11% higher for those treated with terlipressin compared with placebo, said K. Rajender Reddy, MD, director of hepatology and medical director of liver transplantation at the University of Pennsylvania, Philadelphia.

“Hepatorenal syndrome type 1 is a potentially reversible form of acute kidney injury that occurs in the setting of end-stage liver disease,” he said.

Liver transplantation, which eliminates end-stage liver disease, is the only definitive treatment for HRS. However, renal replacement therapy is common and associated with poor clinical outcomes and low patient survival rates in both the pretransplant and posttransplant settings, he noted.

Terlipressin, an injectable synthetic vasopressin analogue, restores renal blood flow and reverses HRS in 20%-40% of patients, Dr. Reddy said. In September, the U.S. Food and Drug Administration approved terlipressin (Terlivaz) for patients with HRS type 1. The label has a boxed warning for serious or fatal respiratory failure.

The safety and efficacy were assessed in the phase 3 CONFIRM trial, which Dr. Reddy and colleagues previously published. The randomized, placebo-controlled study demonstrated that terlipressin reversed HRS and reduced the need for RRT through day 30. The reversal of HRS with terlipressin did not improve 90-day survival as compared with placebo, which researchers attributed to a higher death rate within 90 days after the first dose despite improved kidney function.

A closer look at the liver transplant patients

In the subgroup analysis of the CONFIRM study, Dr. Reddy and colleagues analyzed the clinical outcomes through 12 months of follow-up in patients with HRS who received a liver transplant. They looked at the incidence of verified HRS reversal, HRS reversal, need for RRT, and overall survival.

Verified HRS reversal was defined as two consecutive serum creatinine measurements of 1.5 mg/dL or less at least 2 hours apart up to day 14 and survival without RRT for at least 10 days. HRS reversal was defined as a serum creatinine level of 1.5 mg/dL or less while on treatment. In addition, the need for RRT and overall survival were assessed at days 30, 60, 90, 180, and 365.

RRT was defined as any procedure that replaced nonendocrine kidney function, including continuous hemofiltration and hemodialysis, intermittent hemodialysis, peritoneal dialysis, ultrafiltration, or other dialysis and filtration techniques.

In the CONFIRM study, 199 patients with HRS were treated with terlipressin plus albumin, and 101 patients were treated with placebo plus albumin for up to 14 days. In the terlipressin group, 46 patients received liver transplants within the first 2 months of the study, as did 29 in the placebo group. Two patients in the terlipressin group and one in the placebo group received a simultaneous liver-kidney transplant.
 

Meaningful clinical outcomes

In the 12-month follow-up subgroup analysis, verified HRS reversal was statistically comparable between the groups, with a 30% decrease in the terlipressin group and 17% decrease in the placebo group, Dr. Reddy reported.

HRS reversal was higher in the terlipressin group, at 37%, as compared with 14% in the placebo group.

The pretransplant need for RRT was lower in the terlipressin group, at 30%, as compared with 62% in the placebo group. The posttransplant need for RRT remained numerically lower in the terlipressin group at all time points and was significantly lower at day 180 and day 365.

Overall survival for transplant recipients in the terlipressin group was 94%, as compared with 83% in the placebo group. Posttreatment adverse events and severe adverse events were similar between the groups.

“Collectively, these data indicate that terlipressin treatment in patients with HRS led to better long-term clinical outcomes in those who received a liver transplant,” Dr. Reddy said.

The study was funded by Mallinckrodt Pharmaceuticals, which manufactures terlipressin. One author is an employee of Mallinckrodt, and the other authors have served in an advisory role or received grant support from Mallinckrodt. The authors also disclosed consultant roles and research support from several other pharmaceutical companies.

In a subgroup of patients with hepatorenal syndrome type 1 (HRS) who received a liver transplant, terlipressin treatment appears to reduce the need for renal replacement therapy (RRT) through 12 months of follow-up, according to a study presented at the annual meeting of the American College of Gastroenterology.

Among transplant recipients, overall 12-month survival was 11% higher for those treated with terlipressin compared with placebo, said K. Rajender Reddy, MD, director of hepatology and medical director of liver transplantation at the University of Pennsylvania, Philadelphia.

“Hepatorenal syndrome type 1 is a potentially reversible form of acute kidney injury that occurs in the setting of end-stage liver disease,” he said.

Liver transplantation, which eliminates end-stage liver disease, is the only definitive treatment for HRS. However, renal replacement therapy is common and associated with poor clinical outcomes and low patient survival rates in both the pretransplant and posttransplant settings, he noted.

Terlipressin, an injectable synthetic vasopressin analogue, restores renal blood flow and reverses HRS in 20%-40% of patients, Dr. Reddy said. In September, the U.S. Food and Drug Administration approved terlipressin (Terlivaz) for patients with HRS type 1. The label has a boxed warning for serious or fatal respiratory failure.

The safety and efficacy were assessed in the phase 3 CONFIRM trial, which Dr. Reddy and colleagues previously published. The randomized, placebo-controlled study demonstrated that terlipressin reversed HRS and reduced the need for RRT through day 30. The reversal of HRS with terlipressin did not improve 90-day survival as compared with placebo, which researchers attributed to a higher death rate within 90 days after the first dose despite improved kidney function.

A closer look at the liver transplant patients

In the subgroup analysis of the CONFIRM study, Dr. Reddy and colleagues analyzed the clinical outcomes through 12 months of follow-up in patients with HRS who received a liver transplant. They looked at the incidence of verified HRS reversal, HRS reversal, need for RRT, and overall survival.

Verified HRS reversal was defined as two consecutive serum creatinine measurements of 1.5 mg/dL or less at least 2 hours apart up to day 14 and survival without RRT for at least 10 days. HRS reversal was defined as a serum creatinine level of 1.5 mg/dL or less while on treatment. In addition, the need for RRT and overall survival were assessed at days 30, 60, 90, 180, and 365.

RRT was defined as any procedure that replaced nonendocrine kidney function, including continuous hemofiltration and hemodialysis, intermittent hemodialysis, peritoneal dialysis, ultrafiltration, or other dialysis and filtration techniques.

In the CONFIRM study, 199 patients with HRS were treated with terlipressin plus albumin, and 101 patients were treated with placebo plus albumin for up to 14 days. In the terlipressin group, 46 patients received liver transplants within the first 2 months of the study, as did 29 in the placebo group. Two patients in the terlipressin group and one in the placebo group received a simultaneous liver-kidney transplant.
 

Meaningful clinical outcomes

In the 12-month follow-up subgroup analysis, verified HRS reversal was statistically comparable between the groups, with a 30% decrease in the terlipressin group and 17% decrease in the placebo group, Dr. Reddy reported.

HRS reversal was higher in the terlipressin group, at 37%, as compared with 14% in the placebo group.

The pretransplant need for RRT was lower in the terlipressin group, at 30%, as compared with 62% in the placebo group. The posttransplant need for RRT remained numerically lower in the terlipressin group at all time points and was significantly lower at day 180 and day 365.

Overall survival for transplant recipients in the terlipressin group was 94%, as compared with 83% in the placebo group. Posttreatment adverse events and severe adverse events were similar between the groups.

“Collectively, these data indicate that terlipressin treatment in patients with HRS led to better long-term clinical outcomes in those who received a liver transplant,” Dr. Reddy said.

The study was funded by Mallinckrodt Pharmaceuticals, which manufactures terlipressin. One author is an employee of Mallinckrodt, and the other authors have served in an advisory role or received grant support from Mallinckrodt. The authors also disclosed consultant roles and research support from several other pharmaceutical companies.

Pancreatic cancer screening appears to be safe and effective for certain patients with high-risk indications due to genetic susceptibility, according to a prospective multicenter study presented at the annual meeting of the American College of Gastroenterology.

Screening in high-risk patients detected high-risk lesions in 0.8% of patients, which was lower than the typical range found in the literature, at 3%, said Andy Silva-Santisteban, MD, a research fellow at Beth Israel Deaconess Medical Center at Harvard Medical School in Boston.

Pancreatic cancer is the third leading cause of cancer death in the U.S., which is estimated to become the second leading cause by 2030. About 15%-20% of patients are candidates for surgical resection at the time of diagnosis, with survival rates below 10%.

“These statistics have led pancreatic cancer screening to be studied with the goal of detecting earlier stages of the disease to improve survival,” Dr. Silva-Santisteban said. “However, pancreatic cancer screening is not recommended for the general population.”

Pancreatic cancer screening is recommended for patients with increased risk due to genetic susceptibility, yet recent studies have found that screening studies face limitations from factors like small sample sizes, single-center focus, retrospective nature, nonconsecutive accrual of patients, varied inclusion criteria, and use of nonstandardized screening protocols.

To overcome these limitations, Dr. Silva-Santisteban and colleagues conducted a prospective multicenter study of pancreatic cancer screening in consecutive high-risk patients at five centers in the United States between 2020 and 2022, also called the Pancreas Scan Study. Dr. Silva-Santisteban presented results from the first round of enrollment, which was awarded the Outstanding Research Award in the Biliary/Pancreas Category for Trainee.

The research team evaluated the yield (low-, moderate-, and high-risk pancreatic pathology), safety, and outcomes of screening. Low-risk pancreas pathology was categorized as fatty pancreas and chronic pancreatitis-like changes. Intermediate-risk was categorized as branch duct–intraductal papillary mucinous neoplasm or neuroendocrine tumor under 2 cm. High-risk was categorized as main duct–intraductal papillary mucinous neoplasm (MD-IPMN), pancreatic intraepithelial neoplasia grade III (PanIN-III)/dysplasia, neuroendocrine tumor over 2 cm, or pancreatic cancer.

Patients were included if they were 18 years or older and had at least one of the following: BRCA1, BRCA2, or PALB2 plus a family history of pancreatic cancer; Lynch syndrome plus a family history of pancreatic cancer; Peutz-Jeghers syndrome; familial atypical multiple mole melanoma (FAMMM); ataxia telangiectasia mutated plus family history of pancreatic cancer; hereditary pancreatitis; or familial pancreatic cancer (FPC) syndrome.

Pancreatic cancer screening appears to be safe and effective for certain patients with high-risk indications due to genetic susceptibility, according to a prospective multicenter study presented at the annual meeting of the American College of Gastroenterology.

Screening in high-risk patients detected high-risk lesions in 0.8% of patients, which was lower than the typical range found in the literature, at 3%, said Andy Silva-Santisteban, MD, a research fellow at Beth Israel Deaconess Medical Center at Harvard Medical School in Boston.

Pancreatic cancer is the third leading cause of cancer death in the U.S., which is estimated to become the second leading cause by 2030. About 15%-20% of patients are candidates for surgical resection at the time of diagnosis, with survival rates below 10%.

“These statistics have led pancreatic cancer screening to be studied with the goal of detecting earlier stages of the disease to improve survival,” Dr. Silva-Santisteban said. “However, pancreatic cancer screening is not recommended for the general population.”

Pancreatic cancer screening is recommended for patients with increased risk due to genetic susceptibility, yet recent studies have found that screening studies face limitations from factors like small sample sizes, single-center focus, retrospective nature, nonconsecutive accrual of patients, varied inclusion criteria, and use of nonstandardized screening protocols.

To overcome these limitations, Dr. Silva-Santisteban and colleagues conducted a prospective multicenter study of pancreatic cancer screening in consecutive high-risk patients at five centers in the United States between 2020 and 2022, also called the Pancreas Scan Study. Dr. Silva-Santisteban presented results from the first round of enrollment, which was awarded the Outstanding Research Award in the Biliary/Pancreas Category for Trainee.

The research team evaluated the yield (low-, moderate-, and high-risk pancreatic pathology), safety, and outcomes of screening. Low-risk pancreas pathology was categorized as fatty pancreas and chronic pancreatitis-like changes. Intermediate-risk was categorized as branch duct–intraductal papillary mucinous neoplasm or neuroendocrine tumor under 2 cm. High-risk was categorized as main duct–intraductal papillary mucinous neoplasm (MD-IPMN), pancreatic intraepithelial neoplasia grade III (PanIN-III)/dysplasia, neuroendocrine tumor over 2 cm, or pancreatic cancer.

Patients were included if they were 18 years or older and had at least one of the following: BRCA1, BRCA2, or PALB2 plus a family history of pancreatic cancer; Lynch syndrome plus a family history of pancreatic cancer; Peutz-Jeghers syndrome; familial atypical multiple mole melanoma (FAMMM); ataxia telangiectasia mutated plus family history of pancreatic cancer; hereditary pancreatitis; or familial pancreatic cancer (FPC) syndrome.

Pancreatic cancer screening appears to be safe and effective for certain patients with high-risk indications due to genetic susceptibility, according to a prospective multicenter study presented at the annual meeting of the American College of Gastroenterology.

Screening in high-risk patients detected high-risk lesions in 0.8% of patients, which was lower than the typical range found in the literature, at 3%, said Andy Silva-Santisteban, MD, a research fellow at Beth Israel Deaconess Medical Center at Harvard Medical School in Boston.

Pancreatic cancer is the third leading cause of cancer death in the U.S., which is estimated to become the second leading cause by 2030. About 15%-20% of patients are candidates for surgical resection at the time of diagnosis, with survival rates below 10%.

“These statistics have led pancreatic cancer screening to be studied with the goal of detecting earlier stages of the disease to improve survival,” Dr. Silva-Santisteban said. “However, pancreatic cancer screening is not recommended for the general population.”

Pancreatic cancer screening is recommended for patients with increased risk due to genetic susceptibility, yet recent studies have found that screening studies face limitations from factors like small sample sizes, single-center focus, retrospective nature, nonconsecutive accrual of patients, varied inclusion criteria, and use of nonstandardized screening protocols.

To overcome these limitations, Dr. Silva-Santisteban and colleagues conducted a prospective multicenter study of pancreatic cancer screening in consecutive high-risk patients at five centers in the United States between 2020 and 2022, also called the Pancreas Scan Study. Dr. Silva-Santisteban presented results from the first round of enrollment, which was awarded the Outstanding Research Award in the Biliary/Pancreas Category for Trainee.

The research team evaluated the yield (low-, moderate-, and high-risk pancreatic pathology), safety, and outcomes of screening. Low-risk pancreas pathology was categorized as fatty pancreas and chronic pancreatitis-like changes. Intermediate-risk was categorized as branch duct–intraductal papillary mucinous neoplasm or neuroendocrine tumor under 2 cm. High-risk was categorized as main duct–intraductal papillary mucinous neoplasm (MD-IPMN), pancreatic intraepithelial neoplasia grade III (PanIN-III)/dysplasia, neuroendocrine tumor over 2 cm, or pancreatic cancer.

Patients were included if they were 18 years or older and had at least one of the following: BRCA1, BRCA2, or PALB2 plus a family history of pancreatic cancer; Lynch syndrome plus a family history of pancreatic cancer; Peutz-Jeghers syndrome; familial atypical multiple mole melanoma (FAMMM); ataxia telangiectasia mutated plus family history of pancreatic cancer; hereditary pancreatitis; or familial pancreatic cancer (FPC) syndrome.

Some pediatric patients with celiac disease whose condition is diagnosed after screening because a first-degree relative has the disease may appear asymptomatic but have severe disease histology, according to a new report.

About half of these patients had no symptoms, but disease histology was as severe as among those screened for other reasons, such as having symptomatic disease or high-risk conditions.

“This data supports current recommendations to screen all first-degree relatives of patients with celiac disease, especially pediatric patients in whom the ramifications of untreated disease may be significant,” wrote Michelle Gould, MD, and colleagues at the University of Toronto and McMaster University, Hamilton, Ont.

The study was published online in the Journal of Pediatric Gastroenterology and Nutrition.
 

Clinical characteristics

The incidence of celiac disease is higher among first-degree relatives of patients with the disease than among the general population, yet the clinical characteristics aren’t well described, the study authors wrote. Determining the clinical, serologic, and histologic phenotype of these patients could help clinicians determine whether continued universal screening of first-degree relatives is appropriate.

Dr. Gould and colleagues conducted a retrospective review of 227 patients diagnosed with celiac disease at McMaster Children’s Hospital between 1996 and 2014. The patients were categorized as being screened for celiac disease because a first-degree relative had the disease or because of other reasons. The other reasons included symptoms consistent with celiac disease or the presence of a high-risk clinical condition for which screening is recommended, such as type 1 diabetes or Down syndrome.

All patients were screened via tissue transglutaminase (tTG-IgA) tests. Positive serology was defined as tTG-IgA greater than the upper limit of normal in the presence of normal IgA immunoglobulin level for age.

The patients who were included in the study had biopsy-proven celiac disease in accordance with the Marsh criteria, which included Marsh III histology, Marsh II histology with positive serology, or Marsh I histology with positive serology and clinical symptoms.

The average age of the patients (144 girls and 83 boys) was 8 years at diagnosis. Among the patients, 49 (21.6%) were screened because a first-degree relative had celiac disease. Of those 49 patients, 24 (49%) were symptomatic, and 25 (51%) were asymptomatic.

By contrast, among the 178 patients who were screened for other reasons, 149 (83.7%) were symptomatic, and 29 (16.3%) were asymptomatic.

There was no significant difference between the patient groups with respect to Marsh score at biopsy and tTG-IgA levels at screening. Among the children who were screened because of family history, Marsh scores were equally severe as among other patients, whether they were symptomatic or not.

In addition, no statistically significant differences were found for other clinical characteristics, including body mass index z-score, weight z-score, height z-score, the presence of anemia, or a low mean corpuscular volume for age.

When comparing the characteristics of those screened because of family history and those screened for other high-risk conditions (type 1 diabetes and Down syndrome), the researchers found that rates of asymptomatic presentation were statistically similar between the groups, as were tissue transglutaminase values, Marsh scores, BMI z-scores, and hemoglobin levels at diagnosis. Although there was a statistical difference between the groups with respect to the mean corpuscular volume values at diagnosis, it was unlikely to be of clinical significance, the authors noted.

At 6 months, 1 year, and 2 years after diagnosis, among patients with repeat tTG-IgA measurements, 93 of 143 patients (65%), 52 of 68 patients (76.5%), and 80 of 90 patients (88.9%) had normal serum tTG-IgA levels, respectively. In comparing the proportion of patients whose tTG-IgA levels were normal, there was no difference between those screened because of family history and those screened for other reasons at any time point after diagnosis.

“This may suggest that the natural history of celiac disease is similar in these two groups following initiation of a gluten-free diet and that there are similar rates of compliance with this therapy regardless of the initial indication for screening,” the study authors wrote.
 

Clinical implications

Dr. Gould and colleagues noted that celiac disease was considered histologically severe – with a Marsh III score or higher – among nearly all patients whose condition was diagnosed because of family history. Histology was equally severe regardless of whether the patients were symptomatic or asymptomatic at screening – 100% of symptomatic patients had a high score, and 96% of asymptomatic patients had a high score.

“This emphasizes the importance of celiac screening in all patients with first-degree relatives with celiac disease, as symptom status does not predict diagnosis or severity of disease,” they wrote.

Previous studies have indicated that the prevalence of celiac disease is highest among siblings of patients with celiac disease, compared with other types of first-degree relatives, the authors wrote. However, they lacked this information in their records, which would be valuable for analysis in future studies.

In addition, ongoing research should investigate the optimal frequency of screening for first-degree relatives, they noted.

“One study suggests that individuals screened before 10 years of age should have repeat screening in their second decade for a small increased pick-up of diagnoses,” they wrote.

No funding for the study has been reported. The authors have disclosed no relevant financial relationships.

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

Some pediatric patients with celiac disease whose condition is diagnosed after screening because a first-degree relative has the disease may appear asymptomatic but have severe disease histology, according to a new report.

About half of these patients had no symptoms, but disease histology was as severe as among those screened for other reasons, such as having symptomatic disease or high-risk conditions.

“This data supports current recommendations to screen all first-degree relatives of patients with celiac disease, especially pediatric patients in whom the ramifications of untreated disease may be significant,” wrote Michelle Gould, MD, and colleagues at the University of Toronto and McMaster University, Hamilton, Ont.

The study was published online in the Journal of Pediatric Gastroenterology and Nutrition.
 

Clinical characteristics

The incidence of celiac disease is higher among first-degree relatives of patients with the disease than among the general population, yet the clinical characteristics aren’t well described, the study authors wrote. Determining the clinical, serologic, and histologic phenotype of these patients could help clinicians determine whether continued universal screening of first-degree relatives is appropriate.

Dr. Gould and colleagues conducted a retrospective review of 227 patients diagnosed with celiac disease at McMaster Children’s Hospital between 1996 and 2014. The patients were categorized as being screened for celiac disease because a first-degree relative had the disease or because of other reasons. The other reasons included symptoms consistent with celiac disease or the presence of a high-risk clinical condition for which screening is recommended, such as type 1 diabetes or Down syndrome.

All patients were screened via tissue transglutaminase (tTG-IgA) tests. Positive serology was defined as tTG-IgA greater than the upper limit of normal in the presence of normal IgA immunoglobulin level for age.

The patients who were included in the study had biopsy-proven celiac disease in accordance with the Marsh criteria, which included Marsh III histology, Marsh II histology with positive serology, or Marsh I histology with positive serology and clinical symptoms.

The average age of the patients (144 girls and 83 boys) was 8 years at diagnosis. Among the patients, 49 (21.6%) were screened because a first-degree relative had celiac disease. Of those 49 patients, 24 (49%) were symptomatic, and 25 (51%) were asymptomatic.

By contrast, among the 178 patients who were screened for other reasons, 149 (83.7%) were symptomatic, and 29 (16.3%) were asymptomatic.

There was no significant difference between the patient groups with respect to Marsh score at biopsy and tTG-IgA levels at screening. Among the children who were screened because of family history, Marsh scores were equally severe as among other patients, whether they were symptomatic or not.

In addition, no statistically significant differences were found for other clinical characteristics, including body mass index z-score, weight z-score, height z-score, the presence of anemia, or a low mean corpuscular volume for age.

When comparing the characteristics of those screened because of family history and those screened for other high-risk conditions (type 1 diabetes and Down syndrome), the researchers found that rates of asymptomatic presentation were statistically similar between the groups, as were tissue transglutaminase values, Marsh scores, BMI z-scores, and hemoglobin levels at diagnosis. Although there was a statistical difference between the groups with respect to the mean corpuscular volume values at diagnosis, it was unlikely to be of clinical significance, the authors noted.

At 6 months, 1 year, and 2 years after diagnosis, among patients with repeat tTG-IgA measurements, 93 of 143 patients (65%), 52 of 68 patients (76.5%), and 80 of 90 patients (88.9%) had normal serum tTG-IgA levels, respectively. In comparing the proportion of patients whose tTG-IgA levels were normal, there was no difference between those screened because of family history and those screened for other reasons at any time point after diagnosis.

“This may suggest that the natural history of celiac disease is similar in these two groups following initiation of a gluten-free diet and that there are similar rates of compliance with this therapy regardless of the initial indication for screening,” the study authors wrote.
 

Clinical implications

Dr. Gould and colleagues noted that celiac disease was considered histologically severe – with a Marsh III score or higher – among nearly all patients whose condition was diagnosed because of family history. Histology was equally severe regardless of whether the patients were symptomatic or asymptomatic at screening – 100% of symptomatic patients had a high score, and 96% of asymptomatic patients had a high score.

“This emphasizes the importance of celiac screening in all patients with first-degree relatives with celiac disease, as symptom status does not predict diagnosis or severity of disease,” they wrote.

Previous studies have indicated that the prevalence of celiac disease is highest among siblings of patients with celiac disease, compared with other types of first-degree relatives, the authors wrote. However, they lacked this information in their records, which would be valuable for analysis in future studies.

In addition, ongoing research should investigate the optimal frequency of screening for first-degree relatives, they noted.

“One study suggests that individuals screened before 10 years of age should have repeat screening in their second decade for a small increased pick-up of diagnoses,” they wrote.

No funding for the study has been reported. The authors have disclosed no relevant financial relationships.

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

Some pediatric patients with celiac disease whose condition is diagnosed after screening because a first-degree relative has the disease may appear asymptomatic but have severe disease histology, according to a new report.

About half of these patients had no symptoms, but disease histology was as severe as among those screened for other reasons, such as having symptomatic disease or high-risk conditions.

“This data supports current recommendations to screen all first-degree relatives of patients with celiac disease, especially pediatric patients in whom the ramifications of untreated disease may be significant,” wrote Michelle Gould, MD, and colleagues at the University of Toronto and McMaster University, Hamilton, Ont.

The study was published online in the Journal of Pediatric Gastroenterology and Nutrition.
 

Clinical characteristics

The incidence of celiac disease is higher among first-degree relatives of patients with the disease than among the general population, yet the clinical characteristics aren’t well described, the study authors wrote. Determining the clinical, serologic, and histologic phenotype of these patients could help clinicians determine whether continued universal screening of first-degree relatives is appropriate.

Dr. Gould and colleagues conducted a retrospective review of 227 patients diagnosed with celiac disease at McMaster Children’s Hospital between 1996 and 2014. The patients were categorized as being screened for celiac disease because a first-degree relative had the disease or because of other reasons. The other reasons included symptoms consistent with celiac disease or the presence of a high-risk clinical condition for which screening is recommended, such as type 1 diabetes or Down syndrome.

All patients were screened via tissue transglutaminase (tTG-IgA) tests. Positive serology was defined as tTG-IgA greater than the upper limit of normal in the presence of normal IgA immunoglobulin level for age.

The patients who were included in the study had biopsy-proven celiac disease in accordance with the Marsh criteria, which included Marsh III histology, Marsh II histology with positive serology, or Marsh I histology with positive serology and clinical symptoms.

The average age of the patients (144 girls and 83 boys) was 8 years at diagnosis. Among the patients, 49 (21.6%) were screened because a first-degree relative had celiac disease. Of those 49 patients, 24 (49%) were symptomatic, and 25 (51%) were asymptomatic.

By contrast, among the 178 patients who were screened for other reasons, 149 (83.7%) were symptomatic, and 29 (16.3%) were asymptomatic.

There was no significant difference between the patient groups with respect to Marsh score at biopsy and tTG-IgA levels at screening. Among the children who were screened because of family history, Marsh scores were equally severe as among other patients, whether they were symptomatic or not.

In addition, no statistically significant differences were found for other clinical characteristics, including body mass index z-score, weight z-score, height z-score, the presence of anemia, or a low mean corpuscular volume for age.

When comparing the characteristics of those screened because of family history and those screened for other high-risk conditions (type 1 diabetes and Down syndrome), the researchers found that rates of asymptomatic presentation were statistically similar between the groups, as were tissue transglutaminase values, Marsh scores, BMI z-scores, and hemoglobin levels at diagnosis. Although there was a statistical difference between the groups with respect to the mean corpuscular volume values at diagnosis, it was unlikely to be of clinical significance, the authors noted.

At 6 months, 1 year, and 2 years after diagnosis, among patients with repeat tTG-IgA measurements, 93 of 143 patients (65%), 52 of 68 patients (76.5%), and 80 of 90 patients (88.9%) had normal serum tTG-IgA levels, respectively. In comparing the proportion of patients whose tTG-IgA levels were normal, there was no difference between those screened because of family history and those screened for other reasons at any time point after diagnosis.

“This may suggest that the natural history of celiac disease is similar in these two groups following initiation of a gluten-free diet and that there are similar rates of compliance with this therapy regardless of the initial indication for screening,” the study authors wrote.
 

Clinical implications

Dr. Gould and colleagues noted that celiac disease was considered histologically severe – with a Marsh III score or higher – among nearly all patients whose condition was diagnosed because of family history. Histology was equally severe regardless of whether the patients were symptomatic or asymptomatic at screening – 100% of symptomatic patients had a high score, and 96% of asymptomatic patients had a high score.

“This emphasizes the importance of celiac screening in all patients with first-degree relatives with celiac disease, as symptom status does not predict diagnosis or severity of disease,” they wrote.

Previous studies have indicated that the prevalence of celiac disease is highest among siblings of patients with celiac disease, compared with other types of first-degree relatives, the authors wrote. However, they lacked this information in their records, which would be valuable for analysis in future studies.

In addition, ongoing research should investigate the optimal frequency of screening for first-degree relatives, they noted.

“One study suggests that individuals screened before 10 years of age should have repeat screening in their second decade for a small increased pick-up of diagnoses,” they wrote.

No funding for the study has been reported. The authors have disclosed no relevant financial relationships.

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

Findings indicate that vedolizumab is associated with an increased risk for treatment failure in older patients with inflammatory bowel disease (IBD), as compared with tumor necrosis factor (TNF) antagonists, according to a new study published in JAMA Network Open.

Singh_Siddharth_CALIF_web.jpg

Although the incidence and prevalence of IBD among older adults are rapidly increasing, there is a lack of evidence-based treatment guidance for these patients, who represent less than 5% of participants in IBD-related clinical trials, wrote Siddharth Singh, MD, a gastroenterologist and assistant professor of medicine at the University of California, San Diego, and colleagues.

“Older patients are frequently undertreated and mismanaged with long-term corticosteroid use and limited use of steroid-sparing therapies owing to patients’ and clinicians’ concerns about the safety of immunosuppressive therapy,” the authors wrote. “There is considerable need for evidence-based treatment guidance for older patients with IBD.”

Doctor_patient_older man_web.jpg

The researchers undertook an observational study of the comparative effectiveness of vedolizumab versus TNF antagonists (namely infliximab, adalimumab, and golimumab) among older patients with IBD in Denmark. Using the Danish National Patient Register, the authors included 754 patients aged 50 years and older who received treatment between 2005 and 2018.

The primary effectiveness outcome was treatment failure, defined as the composite 1-year risk of IBD-related hospitalization, IBD-related surgery, or a new corticosteroid prescription more than 6 weeks after initiation of treatment with a biologic. Secondary effectiveness outcomes included time to each component included in the composite score.

The primary safety outcome was the risk of serious infections, defined as those that required hospitalization. Secondary safety outcomes were risk of cancer and major adverse cardiovascular or venous thromboembolic events.

The researchers conducted a 1:1 propensity score-matched analysis, accounting for patient, disease, and treatment factors. The 754 patients included 377 incident users of vedolizumab, including 177 with Crohn’s disease; and 377 incident users of TNF antagonists, including 182 with Crohn’s disease. The average follow-up after treatment initiation occurred between 32 and 40 weeks.

Notably, patients treated with vedolizumab were more likely than those treated with TNF antagonists to have multimorbidity, at 16.2% versus 14.1%, and a higher burden of frailty, at 2.7% versus 1.9%. No significant differences were observed in the proportion of patients with recent immunomodulator and corticosteroid exposure.

Overall, vedolizumab was associated with a 31% increased risk of treatment failure (45.4%), compared with TNF antagonists (34.7%). This included an increased risk of IBD-related hospitalization (27.8% versus 16.3%) and IBD-related major abdominal surgery (21.3% versus 8%).

Among patients with Crohn’s disease, vedolizumab was associated with a 77% increased risk of treatment failure, as well as a greater need for corticosteroids. There was no significant difference in the risk of treatment failure or need for corticosteroids in patients with ulcerative colitis

No significant differences were seen in the risk of serious infections between patients treated with vedolizumab or TNF antagonists, at 8.2% versus 8.7%. This didn’t change by IBD phenotype, age at time of biologic therapy initiation, or treatment with biologic monotherapy versus combination therapy with immunomodulators.

The overall incidence of major adverse cardiovascular or venous thromboembolic events was similar among the groups. Rates of new malignant neoplasms were low, with fewer than five events.

In a subgroup analysis based on the Charlson Comorbidity Index, vedolizumab was associated with a 63% increased risk of treatment failure for patients without comorbidities but not for patients with comorbidities.

“This study adds to the body of literature comparing vedolizumab and anti-TNF in older adults. The findings have been mixed, in some part due to differences in study designs,” said Ashwin N. Ananthakrishnan, MBBS, MPH, associate professor of medicine at Harvard Medical School and a gastroenterologist at Massachusetts General Hospital, both in Boston.

Ananthakrishnan_Ashwin_Bosto_web.jpg

Dr. Ananthakrishnan, who wasn’t involved with this study, has previously researched the two treatments and found that they are comparably safe in older adults. In fact, among patients with significant comorbidity, vedolizumab may be safer. However, the Danish study wasn’t powered to describe that, he said. Moreover, patient characteristics and treatment approaches likely differ between the United States and Denmark.

“Overall, the findings are reassuring. Often when we treat older adults, the emphasis is on safety,” he said. “But by highlighting the difference in clinical response rates – their findings being consistent with a study we published a few years ago – it highlights the importance of also considering efficacy and onset of action for specific disease phenotypes in treatment selection.”

Dr. Ananthakrishnan and colleagues are currently developing clinical tools for risk stratification and prognostication in older adults with IBD, including functional and frailty assessments. “Biologically, older adults may be particularly vulnerable to specific treatment risks such as infections and cancer, but they are also vulnerable to the consequences of untreated disease, including loss of functional independence and frailty,” he explained. “Thus, arriving at the right risk to benefit balance is critically important when making treatment decisions for older adults.”

The study by Dr. Singh and colleagues was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases and the Danish National Research Foundation. Dr. Singh reported receiving grants from pharmaceutical companies unrelated to the study, as well as support from the International Organization for the Study of Inflammatory Bowel Disease Operating Grant and Litwin Pioneers in IBD. No other disclosures were reported. Dr. Ananthakrishnan reported no relevant disclosures.

Findings indicate that vedolizumab is associated with an increased risk for treatment failure in older patients with inflammatory bowel disease (IBD), as compared with tumor necrosis factor (TNF) antagonists, according to a new study published in JAMA Network Open.

Singh_Siddharth_CALIF_web.jpg

Although the incidence and prevalence of IBD among older adults are rapidly increasing, there is a lack of evidence-based treatment guidance for these patients, who represent less than 5% of participants in IBD-related clinical trials, wrote Siddharth Singh, MD, a gastroenterologist and assistant professor of medicine at the University of California, San Diego, and colleagues.

“Older patients are frequently undertreated and mismanaged with long-term corticosteroid use and limited use of steroid-sparing therapies owing to patients’ and clinicians’ concerns about the safety of immunosuppressive therapy,” the authors wrote. “There is considerable need for evidence-based treatment guidance for older patients with IBD.”

Doctor_patient_older man_web.jpg

The researchers undertook an observational study of the comparative effectiveness of vedolizumab versus TNF antagonists (namely infliximab, adalimumab, and golimumab) among older patients with IBD in Denmark. Using the Danish National Patient Register, the authors included 754 patients aged 50 years and older who received treatment between 2005 and 2018.

The primary effectiveness outcome was treatment failure, defined as the composite 1-year risk of IBD-related hospitalization, IBD-related surgery, or a new corticosteroid prescription more than 6 weeks after initiation of treatment with a biologic. Secondary effectiveness outcomes included time to each component included in the composite score.

The primary safety outcome was the risk of serious infections, defined as those that required hospitalization. Secondary safety outcomes were risk of cancer and major adverse cardiovascular or venous thromboembolic events.

The researchers conducted a 1:1 propensity score-matched analysis, accounting for patient, disease, and treatment factors. The 754 patients included 377 incident users of vedolizumab, including 177 with Crohn’s disease; and 377 incident users of TNF antagonists, including 182 with Crohn’s disease. The average follow-up after treatment initiation occurred between 32 and 40 weeks.

Notably, patients treated with vedolizumab were more likely than those treated with TNF antagonists to have multimorbidity, at 16.2% versus 14.1%, and a higher burden of frailty, at 2.7% versus 1.9%. No significant differences were observed in the proportion of patients with recent immunomodulator and corticosteroid exposure.

Overall, vedolizumab was associated with a 31% increased risk of treatment failure (45.4%), compared with TNF antagonists (34.7%). This included an increased risk of IBD-related hospitalization (27.8% versus 16.3%) and IBD-related major abdominal surgery (21.3% versus 8%).

Among patients with Crohn’s disease, vedolizumab was associated with a 77% increased risk of treatment failure, as well as a greater need for corticosteroids. There was no significant difference in the risk of treatment failure or need for corticosteroids in patients with ulcerative colitis

No significant differences were seen in the risk of serious infections between patients treated with vedolizumab or TNF antagonists, at 8.2% versus 8.7%. This didn’t change by IBD phenotype, age at time of biologic therapy initiation, or treatment with biologic monotherapy versus combination therapy with immunomodulators.

The overall incidence of major adverse cardiovascular or venous thromboembolic events was similar among the groups. Rates of new malignant neoplasms were low, with fewer than five events.

In a subgroup analysis based on the Charlson Comorbidity Index, vedolizumab was associated with a 63% increased risk of treatment failure for patients without comorbidities but not for patients with comorbidities.

“This study adds to the body of literature comparing vedolizumab and anti-TNF in older adults. The findings have been mixed, in some part due to differences in study designs,” said Ashwin N. Ananthakrishnan, MBBS, MPH, associate professor of medicine at Harvard Medical School and a gastroenterologist at Massachusetts General Hospital, both in Boston.

Ananthakrishnan_Ashwin_Bosto_web.jpg

Dr. Ananthakrishnan, who wasn’t involved with this study, has previously researched the two treatments and found that they are comparably safe in older adults. In fact, among patients with significant comorbidity, vedolizumab may be safer. However, the Danish study wasn’t powered to describe that, he said. Moreover, patient characteristics and treatment approaches likely differ between the United States and Denmark.

“Overall, the findings are reassuring. Often when we treat older adults, the emphasis is on safety,” he said. “But by highlighting the difference in clinical response rates – their findings being consistent with a study we published a few years ago – it highlights the importance of also considering efficacy and onset of action for specific disease phenotypes in treatment selection.”

Dr. Ananthakrishnan and colleagues are currently developing clinical tools for risk stratification and prognostication in older adults with IBD, including functional and frailty assessments. “Biologically, older adults may be particularly vulnerable to specific treatment risks such as infections and cancer, but they are also vulnerable to the consequences of untreated disease, including loss of functional independence and frailty,” he explained. “Thus, arriving at the right risk to benefit balance is critically important when making treatment decisions for older adults.”

The study by Dr. Singh and colleagues was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases and the Danish National Research Foundation. Dr. Singh reported receiving grants from pharmaceutical companies unrelated to the study, as well as support from the International Organization for the Study of Inflammatory Bowel Disease Operating Grant and Litwin Pioneers in IBD. No other disclosures were reported. Dr. Ananthakrishnan reported no relevant disclosures.

Findings indicate that vedolizumab is associated with an increased risk for treatment failure in older patients with inflammatory bowel disease (IBD), as compared with tumor necrosis factor (TNF) antagonists, according to a new study published in JAMA Network Open.

Singh_Siddharth_CALIF_web.jpg

Although the incidence and prevalence of IBD among older adults are rapidly increasing, there is a lack of evidence-based treatment guidance for these patients, who represent less than 5% of participants in IBD-related clinical trials, wrote Siddharth Singh, MD, a gastroenterologist and assistant professor of medicine at the University of California, San Diego, and colleagues.

“Older patients are frequently undertreated and mismanaged with long-term corticosteroid use and limited use of steroid-sparing therapies owing to patients’ and clinicians’ concerns about the safety of immunosuppressive therapy,” the authors wrote. “There is considerable need for evidence-based treatment guidance for older patients with IBD.”

Doctor_patient_older man_web.jpg

The researchers undertook an observational study of the comparative effectiveness of vedolizumab versus TNF antagonists (namely infliximab, adalimumab, and golimumab) among older patients with IBD in Denmark. Using the Danish National Patient Register, the authors included 754 patients aged 50 years and older who received treatment between 2005 and 2018.

The primary effectiveness outcome was treatment failure, defined as the composite 1-year risk of IBD-related hospitalization, IBD-related surgery, or a new corticosteroid prescription more than 6 weeks after initiation of treatment with a biologic. Secondary effectiveness outcomes included time to each component included in the composite score.

The primary safety outcome was the risk of serious infections, defined as those that required hospitalization. Secondary safety outcomes were risk of cancer and major adverse cardiovascular or venous thromboembolic events.

The researchers conducted a 1:1 propensity score-matched analysis, accounting for patient, disease, and treatment factors. The 754 patients included 377 incident users of vedolizumab, including 177 with Crohn’s disease; and 377 incident users of TNF antagonists, including 182 with Crohn’s disease. The average follow-up after treatment initiation occurred between 32 and 40 weeks.

Notably, patients treated with vedolizumab were more likely than those treated with TNF antagonists to have multimorbidity, at 16.2% versus 14.1%, and a higher burden of frailty, at 2.7% versus 1.9%. No significant differences were observed in the proportion of patients with recent immunomodulator and corticosteroid exposure.

Overall, vedolizumab was associated with a 31% increased risk of treatment failure (45.4%), compared with TNF antagonists (34.7%). This included an increased risk of IBD-related hospitalization (27.8% versus 16.3%) and IBD-related major abdominal surgery (21.3% versus 8%).

Among patients with Crohn’s disease, vedolizumab was associated with a 77% increased risk of treatment failure, as well as a greater need for corticosteroids. There was no significant difference in the risk of treatment failure or need for corticosteroids in patients with ulcerative colitis

No significant differences were seen in the risk of serious infections between patients treated with vedolizumab or TNF antagonists, at 8.2% versus 8.7%. This didn’t change by IBD phenotype, age at time of biologic therapy initiation, or treatment with biologic monotherapy versus combination therapy with immunomodulators.

The overall incidence of major adverse cardiovascular or venous thromboembolic events was similar among the groups. Rates of new malignant neoplasms were low, with fewer than five events.

In a subgroup analysis based on the Charlson Comorbidity Index, vedolizumab was associated with a 63% increased risk of treatment failure for patients without comorbidities but not for patients with comorbidities.

“This study adds to the body of literature comparing vedolizumab and anti-TNF in older adults. The findings have been mixed, in some part due to differences in study designs,” said Ashwin N. Ananthakrishnan, MBBS, MPH, associate professor of medicine at Harvard Medical School and a gastroenterologist at Massachusetts General Hospital, both in Boston.

Ananthakrishnan_Ashwin_Bosto_web.jpg

Dr. Ananthakrishnan, who wasn’t involved with this study, has previously researched the two treatments and found that they are comparably safe in older adults. In fact, among patients with significant comorbidity, vedolizumab may be safer. However, the Danish study wasn’t powered to describe that, he said. Moreover, patient characteristics and treatment approaches likely differ between the United States and Denmark.

“Overall, the findings are reassuring. Often when we treat older adults, the emphasis is on safety,” he said. “But by highlighting the difference in clinical response rates – their findings being consistent with a study we published a few years ago – it highlights the importance of also considering efficacy and onset of action for specific disease phenotypes in treatment selection.”

Dr. Ananthakrishnan and colleagues are currently developing clinical tools for risk stratification and prognostication in older adults with IBD, including functional and frailty assessments. “Biologically, older adults may be particularly vulnerable to specific treatment risks such as infections and cancer, but they are also vulnerable to the consequences of untreated disease, including loss of functional independence and frailty,” he explained. “Thus, arriving at the right risk to benefit balance is critically important when making treatment decisions for older adults.”

The study by Dr. Singh and colleagues was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases and the Danish National Research Foundation. Dr. Singh reported receiving grants from pharmaceutical companies unrelated to the study, as well as support from the International Organization for the Study of Inflammatory Bowel Disease Operating Grant and Litwin Pioneers in IBD. No other disclosures were reported. Dr. Ananthakrishnan reported no relevant disclosures.

Patients’ reports of remission from inflammatory bowel disease (IBD) don’t always line up with remission as defined by patient-reported outcomes (PROs) or physician global assessment (PGA), according to a study published in Inflammatory Bowel Diseases.

doctor_patient_2_web.jpg

Patients have various definitions of remission, which may focus on symptom improvement and the impact on daily activities, while physicians tend to focus on test results. “Examining patient-reported remission may be a valuable approach to better understand remission from the perspective of patients and can assist in aligning shared decision-making between patients and health care providers,” wrote Kendra Kamp, PhD, assistant professor of biobehavioral nursing and health informatics at the University of Washington, and colleagues, on behalf of the IBD Qorus.

In a retrospective study, Dr. Kamp and colleagues analyzed 3,257 deidentified surveys from 2,004 patients who participated in the Crohn’s and Colitis Foundation’s IBD Qorus Learning Health System between September 2019 and February 2021. Adults with IBD who participated in the IBD Qorus received an email before their gastroenterology clinical appointment with a link to a survey that asked questions about primary concerns or goals, symptoms, well-being, recent health care utilization, and medication use.

Kendra_Kamp_WASH_web.jpg

The researchers looked at the clinical and demographic factors associated with discordance among patient-defined remission, PROs, and PGAs. Patient-defined remission was captured as a yes/no response to the question: “Do you feel your disease is currently in remission (by remission we mean a complete absence of IBD-related symptoms)?”

PROs for ulcerative colitis were measured through stool frequency and rectal bleeding, with remission defined as no blood in the stool and a normal (or fewer than normal) number of stools. For Crohn’s disease, PROs were measured through the average number of liquid stools, abdominal pain, and general well-being, with remission defined as two or fewer loose stools, no or mild abdominal pain, and feeling generally well or slightly under par.

For PGAs, clinicians selected whether the patient had normal, mild, moderate, or severe disease activity. The values were included in the analysis if the clinicians completed the assessment within 14 days of the patient’s survey.

Among the 2,004 patients, 806 had ulcerative colitis and 1,198 had Crohn’s disease. Patients with ulcerative colitis as well as those with Crohn’s disease were aged 44 years on average. Most of the patients were women: 58% with ulcerative colitis and 56% with Crohn’s disease.

Among the 1,316 visits for ulcerative colitis, 668 patients (51%) self-reported to be in remission, compared with 55% in remission based on PROs. Of the people in PRO–defined remission, 77% reported being in remission, and 23% reported active disease. Of the people with PRO–defined active disease, 81% reported active disease and 19% reported remission. Overall concordance was 79% between patient self-reported and PRO–defined remission.

Discordance in patient-defined remission for ulcerative colitis was primarily influenced by tolerance of an increased stool frequency. About 25% of patients with one or two stools more than normal reported being in remission.

A subset of 397 ulcerative colitis visits had an associated PGA score. Among patients in PGA-defined remission, 53% reported being in remission. Of those with PGA-defined active disease, 60% reported active disease. Overall, concordance was 49% between patient self-reported and PGA-defined remission.

Among the 1,947 visits for Crohn’s disease, 929 patients (48%) self-reported to be in remission, compared with 63% in remission based on PRO. Of the people in PRO-defined remission, 63% reported being in remission, although 37% reported active disease. Of the people with PRO-defined active disease, 79% reported active disease and 21% reported remission. Overall concordance was 69% between patient self-reported and patient-reported outcomes–defined remission.

Discordance in patient-defined remission for Crohn’s disease was primarily influenced by patients with a tolerance of mild to moderate symptoms.

A subset of 575 Crohn’s disease visits had an associated PGA score. Among patients in PGA-defined remission, 52% reported being in remission. Of those with PGA-defined active disease, 57% reported active disease. Overall concordance was 54% between patient self-reported and PGA-defined remission.

Several factors were associated with discordance in remission definitions. Among patients in PRO-defined remission, those who had a diagnosis of IBD for fewer than 5 years were more likely to report having active disease compared with those who had received a diagnosis more than 15 years before.

Patients with high health confidence in managing their condition were less likely to report having active disease. In addition, patients with Crohn’s disease were more likely to report having active disease if they were using prednisone or opioids or if they had an IBD-related emergency department visit in the past 6 months.

Sadeea_Abbasi_CALIF_web.jpg

Patients’ reports of remission from inflammatory bowel disease (IBD) don’t always line up with remission as defined by patient-reported outcomes (PROs) or physician global assessment (PGA), according to a study published in Inflammatory Bowel Diseases.

doctor_patient_2_web.jpg

Patients have various definitions of remission, which may focus on symptom improvement and the impact on daily activities, while physicians tend to focus on test results. “Examining patient-reported remission may be a valuable approach to better understand remission from the perspective of patients and can assist in aligning shared decision-making between patients and health care providers,” wrote Kendra Kamp, PhD, assistant professor of biobehavioral nursing and health informatics at the University of Washington, and colleagues, on behalf of the IBD Qorus.

In a retrospective study, Dr. Kamp and colleagues analyzed 3,257 deidentified surveys from 2,004 patients who participated in the Crohn’s and Colitis Foundation’s IBD Qorus Learning Health System between September 2019 and February 2021. Adults with IBD who participated in the IBD Qorus received an email before their gastroenterology clinical appointment with a link to a survey that asked questions about primary concerns or goals, symptoms, well-being, recent health care utilization, and medication use.

Kendra_Kamp_WASH_web.jpg

The researchers looked at the clinical and demographic factors associated with discordance among patient-defined remission, PROs, and PGAs. Patient-defined remission was captured as a yes/no response to the question: “Do you feel your disease is currently in remission (by remission we mean a complete absence of IBD-related symptoms)?”

PROs for ulcerative colitis were measured through stool frequency and rectal bleeding, with remission defined as no blood in the stool and a normal (or fewer than normal) number of stools. For Crohn’s disease, PROs were measured through the average number of liquid stools, abdominal pain, and general well-being, with remission defined as two or fewer loose stools, no or mild abdominal pain, and feeling generally well or slightly under par.

For PGAs, clinicians selected whether the patient had normal, mild, moderate, or severe disease activity. The values were included in the analysis if the clinicians completed the assessment within 14 days of the patient’s survey.

Among the 2,004 patients, 806 had ulcerative colitis and 1,198 had Crohn’s disease. Patients with ulcerative colitis as well as those with Crohn’s disease were aged 44 years on average. Most of the patients were women: 58% with ulcerative colitis and 56% with Crohn’s disease.

Among the 1,316 visits for ulcerative colitis, 668 patients (51%) self-reported to be in remission, compared with 55% in remission based on PROs. Of the people in PRO–defined remission, 77% reported being in remission, and 23% reported active disease. Of the people with PRO–defined active disease, 81% reported active disease and 19% reported remission. Overall concordance was 79% between patient self-reported and PRO–defined remission.

Discordance in patient-defined remission for ulcerative colitis was primarily influenced by tolerance of an increased stool frequency. About 25% of patients with one or two stools more than normal reported being in remission.

A subset of 397 ulcerative colitis visits had an associated PGA score. Among patients in PGA-defined remission, 53% reported being in remission. Of those with PGA-defined active disease, 60% reported active disease. Overall, concordance was 49% between patient self-reported and PGA-defined remission.

Among the 1,947 visits for Crohn’s disease, 929 patients (48%) self-reported to be in remission, compared with 63% in remission based on PRO. Of the people in PRO-defined remission, 63% reported being in remission, although 37% reported active disease. Of the people with PRO-defined active disease, 79% reported active disease and 21% reported remission. Overall concordance was 69% between patient self-reported and patient-reported outcomes–defined remission.

Discordance in patient-defined remission for Crohn’s disease was primarily influenced by patients with a tolerance of mild to moderate symptoms.

A subset of 575 Crohn’s disease visits had an associated PGA score. Among patients in PGA-defined remission, 52% reported being in remission. Of those with PGA-defined active disease, 57% reported active disease. Overall concordance was 54% between patient self-reported and PGA-defined remission.

Several factors were associated with discordance in remission definitions. Among patients in PRO-defined remission, those who had a diagnosis of IBD for fewer than 5 years were more likely to report having active disease compared with those who had received a diagnosis more than 15 years before.

Patients with high health confidence in managing their condition were less likely to report having active disease. In addition, patients with Crohn’s disease were more likely to report having active disease if they were using prednisone or opioids or if they had an IBD-related emergency department visit in the past 6 months.

Sadeea_Abbasi_CALIF_web.jpg

Patients’ reports of remission from inflammatory bowel disease (IBD) don’t always line up with remission as defined by patient-reported outcomes (PROs) or physician global assessment (PGA), according to a study published in Inflammatory Bowel Diseases.

doctor_patient_2_web.jpg

Patients have various definitions of remission, which may focus on symptom improvement and the impact on daily activities, while physicians tend to focus on test results. “Examining patient-reported remission may be a valuable approach to better understand remission from the perspective of patients and can assist in aligning shared decision-making between patients and health care providers,” wrote Kendra Kamp, PhD, assistant professor of biobehavioral nursing and health informatics at the University of Washington, and colleagues, on behalf of the IBD Qorus.

In a retrospective study, Dr. Kamp and colleagues analyzed 3,257 deidentified surveys from 2,004 patients who participated in the Crohn’s and Colitis Foundation’s IBD Qorus Learning Health System between September 2019 and February 2021. Adults with IBD who participated in the IBD Qorus received an email before their gastroenterology clinical appointment with a link to a survey that asked questions about primary concerns or goals, symptoms, well-being, recent health care utilization, and medication use.

Kendra_Kamp_WASH_web.jpg

The researchers looked at the clinical and demographic factors associated with discordance among patient-defined remission, PROs, and PGAs. Patient-defined remission was captured as a yes/no response to the question: “Do you feel your disease is currently in remission (by remission we mean a complete absence of IBD-related symptoms)?”

PROs for ulcerative colitis were measured through stool frequency and rectal bleeding, with remission defined as no blood in the stool and a normal (or fewer than normal) number of stools. For Crohn’s disease, PROs were measured through the average number of liquid stools, abdominal pain, and general well-being, with remission defined as two or fewer loose stools, no or mild abdominal pain, and feeling generally well or slightly under par.

For PGAs, clinicians selected whether the patient had normal, mild, moderate, or severe disease activity. The values were included in the analysis if the clinicians completed the assessment within 14 days of the patient’s survey.

Among the 2,004 patients, 806 had ulcerative colitis and 1,198 had Crohn’s disease. Patients with ulcerative colitis as well as those with Crohn’s disease were aged 44 years on average. Most of the patients were women: 58% with ulcerative colitis and 56% with Crohn’s disease.

Among the 1,316 visits for ulcerative colitis, 668 patients (51%) self-reported to be in remission, compared with 55% in remission based on PROs. Of the people in PRO–defined remission, 77% reported being in remission, and 23% reported active disease. Of the people with PRO–defined active disease, 81% reported active disease and 19% reported remission. Overall concordance was 79% between patient self-reported and PRO–defined remission.

Discordance in patient-defined remission for ulcerative colitis was primarily influenced by tolerance of an increased stool frequency. About 25% of patients with one or two stools more than normal reported being in remission.

A subset of 397 ulcerative colitis visits had an associated PGA score. Among patients in PGA-defined remission, 53% reported being in remission. Of those with PGA-defined active disease, 60% reported active disease. Overall, concordance was 49% between patient self-reported and PGA-defined remission.

Among the 1,947 visits for Crohn’s disease, 929 patients (48%) self-reported to be in remission, compared with 63% in remission based on PRO. Of the people in PRO-defined remission, 63% reported being in remission, although 37% reported active disease. Of the people with PRO-defined active disease, 79% reported active disease and 21% reported remission. Overall concordance was 69% between patient self-reported and patient-reported outcomes–defined remission.

Discordance in patient-defined remission for Crohn’s disease was primarily influenced by patients with a tolerance of mild to moderate symptoms.

A subset of 575 Crohn’s disease visits had an associated PGA score. Among patients in PGA-defined remission, 52% reported being in remission. Of those with PGA-defined active disease, 57% reported active disease. Overall concordance was 54% between patient self-reported and PGA-defined remission.

Several factors were associated with discordance in remission definitions. Among patients in PRO-defined remission, those who had a diagnosis of IBD for fewer than 5 years were more likely to report having active disease compared with those who had received a diagnosis more than 15 years before.

Patients with high health confidence in managing their condition were less likely to report having active disease. In addition, patients with Crohn’s disease were more likely to report having active disease if they were using prednisone or opioids or if they had an IBD-related emergency department visit in the past 6 months.

Sadeea_Abbasi_CALIF_web.jpg

Nearly two-thirds of people who had persistent COVID-19 symptoms during the first 2 years of the pandemic were women, according to a new study published in JAMA.

The global study also found that about 6% of people with symptomatic infections had long COVID in 2020 and 2021. The risk for long COVID seemed to be greater among those who needed hospitalization, especially those who needed intensive care.

“Quantifying the number of individuals with long COVID may help policy makers ensure adequate access to services to guide people toward recovery, return to the workplace or school, and restore their mental health and social life,” the researchers wrote.

The study team, which included dozens of researchers across nearly every continent, analyzed data from 54 studies and two databases for more than 1 million patients in 22 countries who had symptomatic COVID infections in 2020 and 2021. They looked at three long COVID symptom types: persistent fatigue with bodily pain or mood swings, ongoing respiratory problems, and cognitive issues. The study included people aged 4-66.

Overall, 6.2% of people reported one of the long COVID symptom types, including 3.7% with ongoing respiratory problems, 3.2% with persistent fatigue and bodily pain or mood swings, and 2.2% with cognitive problems. Among those with long COVID, 38% of people reported more than one symptom cluster.

At 3 months after infection, long COVID symptoms were nearly twice as common in women who were at least 20 years old at 10.6%, compared with men who were at least 20 years old at 5.4%.

Children and teens appeared to have lower risks of long COVID. About 2.8% of patients under age 20 with symptomatic infection developed long-term issues.

The estimated average duration of long COVID symptoms was 9 months among hospitalized patients and 4 months among those who weren’t hospitalized. About 15% of people with long COVID symptoms 3 months after the initial infection continued to have symptoms at 12 months.

The study was largely based on detailed data from ongoing COVID-19 studies in the United States, Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, and Switzerland, according to UPI. It was supplemented by published data and research conducted as part of the Global Burden of Diseases, Injuries and Risk Factors Study. The dozens of researchers are referred to as “Global Burden of Disease Long COVID Collaborators.”

The study had limitations, the researchers said, including the assumption that long COVID follows a similar course in all countries. Additional studies may show how long COVID symptoms and severity may vary in different countries and continents.

Ultimately, ongoing studies of large numbers of people with long COVID could help scientists and public health officials understand risk factors and ways to treat the debilitating condition, the study authors wrote, noting that “postinfection fatigue syndrome” has been reported before, namely during the 1918 flu pandemic, after the SARS outbreak in 2003, and after the Ebola epidemic in West Africa in 2014.

“Similar symptoms have been reported after other viral infections, including the Epstein-Barr virus, mononucleosis, and dengue, as well as after nonviral infections such as Q fever, Lyme disease and giardiasis,” they wrote.

Several study investigators reported receiving grants and personal fees from a variety of sources.

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

Nearly two-thirds of people who had persistent COVID-19 symptoms during the first 2 years of the pandemic were women, according to a new study published in JAMA.

The global study also found that about 6% of people with symptomatic infections had long COVID in 2020 and 2021. The risk for long COVID seemed to be greater among those who needed hospitalization, especially those who needed intensive care.

“Quantifying the number of individuals with long COVID may help policy makers ensure adequate access to services to guide people toward recovery, return to the workplace or school, and restore their mental health and social life,” the researchers wrote.

The study team, which included dozens of researchers across nearly every continent, analyzed data from 54 studies and two databases for more than 1 million patients in 22 countries who had symptomatic COVID infections in 2020 and 2021. They looked at three long COVID symptom types: persistent fatigue with bodily pain or mood swings, ongoing respiratory problems, and cognitive issues. The study included people aged 4-66.

Overall, 6.2% of people reported one of the long COVID symptom types, including 3.7% with ongoing respiratory problems, 3.2% with persistent fatigue and bodily pain or mood swings, and 2.2% with cognitive problems. Among those with long COVID, 38% of people reported more than one symptom cluster.

At 3 months after infection, long COVID symptoms were nearly twice as common in women who were at least 20 years old at 10.6%, compared with men who were at least 20 years old at 5.4%.

Children and teens appeared to have lower risks of long COVID. About 2.8% of patients under age 20 with symptomatic infection developed long-term issues.

The estimated average duration of long COVID symptoms was 9 months among hospitalized patients and 4 months among those who weren’t hospitalized. About 15% of people with long COVID symptoms 3 months after the initial infection continued to have symptoms at 12 months.

The study was largely based on detailed data from ongoing COVID-19 studies in the United States, Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, and Switzerland, according to UPI. It was supplemented by published data and research conducted as part of the Global Burden of Diseases, Injuries and Risk Factors Study. The dozens of researchers are referred to as “Global Burden of Disease Long COVID Collaborators.”

The study had limitations, the researchers said, including the assumption that long COVID follows a similar course in all countries. Additional studies may show how long COVID symptoms and severity may vary in different countries and continents.

Ultimately, ongoing studies of large numbers of people with long COVID could help scientists and public health officials understand risk factors and ways to treat the debilitating condition, the study authors wrote, noting that “postinfection fatigue syndrome” has been reported before, namely during the 1918 flu pandemic, after the SARS outbreak in 2003, and after the Ebola epidemic in West Africa in 2014.

“Similar symptoms have been reported after other viral infections, including the Epstein-Barr virus, mononucleosis, and dengue, as well as after nonviral infections such as Q fever, Lyme disease and giardiasis,” they wrote.

Several study investigators reported receiving grants and personal fees from a variety of sources.

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

Nearly two-thirds of people who had persistent COVID-19 symptoms during the first 2 years of the pandemic were women, according to a new study published in JAMA.

The global study also found that about 6% of people with symptomatic infections had long COVID in 2020 and 2021. The risk for long COVID seemed to be greater among those who needed hospitalization, especially those who needed intensive care.

“Quantifying the number of individuals with long COVID may help policy makers ensure adequate access to services to guide people toward recovery, return to the workplace or school, and restore their mental health and social life,” the researchers wrote.

The study team, which included dozens of researchers across nearly every continent, analyzed data from 54 studies and two databases for more than 1 million patients in 22 countries who had symptomatic COVID infections in 2020 and 2021. They looked at three long COVID symptom types: persistent fatigue with bodily pain or mood swings, ongoing respiratory problems, and cognitive issues. The study included people aged 4-66.

Overall, 6.2% of people reported one of the long COVID symptom types, including 3.7% with ongoing respiratory problems, 3.2% with persistent fatigue and bodily pain or mood swings, and 2.2% with cognitive problems. Among those with long COVID, 38% of people reported more than one symptom cluster.

At 3 months after infection, long COVID symptoms were nearly twice as common in women who were at least 20 years old at 10.6%, compared with men who were at least 20 years old at 5.4%.

Children and teens appeared to have lower risks of long COVID. About 2.8% of patients under age 20 with symptomatic infection developed long-term issues.

The estimated average duration of long COVID symptoms was 9 months among hospitalized patients and 4 months among those who weren’t hospitalized. About 15% of people with long COVID symptoms 3 months after the initial infection continued to have symptoms at 12 months.

The study was largely based on detailed data from ongoing COVID-19 studies in the United States, Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, and Switzerland, according to UPI. It was supplemented by published data and research conducted as part of the Global Burden of Diseases, Injuries and Risk Factors Study. The dozens of researchers are referred to as “Global Burden of Disease Long COVID Collaborators.”

The study had limitations, the researchers said, including the assumption that long COVID follows a similar course in all countries. Additional studies may show how long COVID symptoms and severity may vary in different countries and continents.

Ultimately, ongoing studies of large numbers of people with long COVID could help scientists and public health officials understand risk factors and ways to treat the debilitating condition, the study authors wrote, noting that “postinfection fatigue syndrome” has been reported before, namely during the 1918 flu pandemic, after the SARS outbreak in 2003, and after the Ebola epidemic in West Africa in 2014.

“Similar symptoms have been reported after other viral infections, including the Epstein-Barr virus, mononucleosis, and dengue, as well as after nonviral infections such as Q fever, Lyme disease and giardiasis,” they wrote.

Several study investigators reported receiving grants and personal fees from a variety of sources.

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

People who eat a balanced diet with sufficient antioxidants from fruits and vegetables may face reduced risks for Heliobacter pylori infections, according to a new report.

In particular, patients with an H. pylori infection were more likely to score lower on the Dietary Antioxidant Index (DAI), which was created to consider a diet’s entire antioxidant profile.

“Available evidence indicates that diet has an important role in developing H. pylori infection. Therefore, protective dietary factors are important from a public health point of view,” Farzad Shidfar, a professor of nutrition at the Iran University of Medical Sciences, Tehran, and member of the university’s colorectal research center, and colleagues write.

“While some nutritional research has widely focused on single nutrients or foods in diet-disease relations, the overall diet could be more informative because humans typically consume a combination of nutrients and foods,” they write. “Dietary indices such as DAI are one of the approaches for this purpose.”

The study was published online in BMC Gastroenterology.
 

Measuring antioxidant intake

Previous research has indicated an inverse association between the DAI and inflammatory diseases, the study authors write, including gastric cancer, colorectal cancer, nonalcoholic fatty liver disease, and obesity. Studies have also indicated that H. pylori infection is related to deficiencies in vitamins A, C, and E, which have antioxidant properties.

In a case-control study, the research team compared the dietary intake of 148 patients with H. pylori to 302 healthy controls without infection. The patients in the H. pylori–positive group were recruited between June 2021 and November 2021 from the gastroenterology clinic at Rasoul-e-Akram Hospital in Tehran, where they were newly diagnosed with active infection and not yet under treatment.

The researchers calculated the DAI based on dietary intake information from a validated, 168-item food frequency questionnaire used in Iran. The participants were asked about their dietary intake based on the average day, week, month, and year. They also discussed serving sizes of food items, and to increase the accuracy of estimates, interviewers showed household measurements or serving sizes to confirm the measurements with participants.

The average age of the study participants was 39 years, and about 60% were women. Compared with the healthy controls, those with H. pylori were significantly older, had higher body mass index, and smoked more.

Overall, patients with H. pylori had a significantly lower intake of vitamin A, vitamin E, manganese, and selenium. Other differences in dietary intake – for vitamin C and zinc – were not significant.

The average total DAI was significantly higher in the healthy controls, at 7.67, as compared with 3.57 in the patients with H. pylori. The risk for infection decreased as continuous DAI increased.

After adjusting for several variables, the researchers found that participants with less than the median DAI values had an increased risk of developing an H. pylori infection.

“A balanced diet, especially high consumption of fruits and vegetables, might protect people against the consequences of H. pylori infection,” the study authors write. “On the contrary, a diet full of carbohydrates and sweets is related to a higher H. pylori infection prevalence.”
 

Why a good diet may help combat infection

The findings are consistent with other studies that have noted a higher intake of fruits and vegetables among healthy people compared with those who have H. pylori infections, the study authors write. Animal studies have also indicated that taking vitamins A, C, and E and selenium can lead to a reduction in H. pylori growth.

“Several biologically plausible reasons may explain why dietary antioxidants might be, either directly or indirectly, a protective factor against H. pylori infection,” the researchers write. “It is well-known that antioxidants, with their free radical scavenging activities, can inhibit the growth of H. pylori.”

H. pylori is urease-positive and can synthesize a large amount of urease for ammonia production to neutralize gastric acid, which allows it to colonize in the stomach epithelium, the study authors write. Vitamin C inhibits urease activity and improves the stimulation of granulocytes, macrophages, lymphocytes, and immunoglobulin production. Other nutrients, such as zinc, may inhibit the urease enzyme and prevent H. pylori adhesion to gastric tissues, they write.

“Dietary elements have previously been shown to dramatically alter pathogenic responses to H. pylori infections,” Richard Peek Jr., MD, professor of medicine and director of gastroenterology at Vanderbilt University Medical Center, Nashville, Tenn., told this news organization.

Dr. Peek, who wasn’t involved with this study, and colleagues found that iron deficiency is linked with altered bile metabolism, which can promote H. pylori–induced gastric carcinogenesis.

“The current study is important, as it suggests that shifting to a diet rich in antioxidants may be beneficial in terms of H. pylori infection,” he said.

At the same time, Dr. Peek expressed caution about generalizing the results across populations.

“Most of the persons enrolled in this study were likely infected with H. pylori as children,” he noted. “Therefore, the inverse role of antioxidant-rich diets and H. pylori infection must be interpreted with caution.”

Future studies should confirm the findings in other groups and determine whether antioxidant-rich diets limit the diseases caused by H. pylori infection, Dr. Peek added.

The study was not funded by any research center, and the authors declared no conflicts of interest. Dr. Peek reported no relevant disclosures.

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

People who eat a balanced diet with sufficient antioxidants from fruits and vegetables may face reduced risks for Heliobacter pylori infections, according to a new report.

In particular, patients with an H. pylori infection were more likely to score lower on the Dietary Antioxidant Index (DAI), which was created to consider a diet’s entire antioxidant profile.

“Available evidence indicates that diet has an important role in developing H. pylori infection. Therefore, protective dietary factors are important from a public health point of view,” Farzad Shidfar, a professor of nutrition at the Iran University of Medical Sciences, Tehran, and member of the university’s colorectal research center, and colleagues write.

“While some nutritional research has widely focused on single nutrients or foods in diet-disease relations, the overall diet could be more informative because humans typically consume a combination of nutrients and foods,” they write. “Dietary indices such as DAI are one of the approaches for this purpose.”

The study was published online in BMC Gastroenterology.
 

Measuring antioxidant intake

Previous research has indicated an inverse association between the DAI and inflammatory diseases, the study authors write, including gastric cancer, colorectal cancer, nonalcoholic fatty liver disease, and obesity. Studies have also indicated that H. pylori infection is related to deficiencies in vitamins A, C, and E, which have antioxidant properties.

In a case-control study, the research team compared the dietary intake of 148 patients with H. pylori to 302 healthy controls without infection. The patients in the H. pylori–positive group were recruited between June 2021 and November 2021 from the gastroenterology clinic at Rasoul-e-Akram Hospital in Tehran, where they were newly diagnosed with active infection and not yet under treatment.

The researchers calculated the DAI based on dietary intake information from a validated, 168-item food frequency questionnaire used in Iran. The participants were asked about their dietary intake based on the average day, week, month, and year. They also discussed serving sizes of food items, and to increase the accuracy of estimates, interviewers showed household measurements or serving sizes to confirm the measurements with participants.

The average age of the study participants was 39 years, and about 60% were women. Compared with the healthy controls, those with H. pylori were significantly older, had higher body mass index, and smoked more.

Overall, patients with H. pylori had a significantly lower intake of vitamin A, vitamin E, manganese, and selenium. Other differences in dietary intake – for vitamin C and zinc – were not significant.

The average total DAI was significantly higher in the healthy controls, at 7.67, as compared with 3.57 in the patients with H. pylori. The risk for infection decreased as continuous DAI increased.

After adjusting for several variables, the researchers found that participants with less than the median DAI values had an increased risk of developing an H. pylori infection.

“A balanced diet, especially high consumption of fruits and vegetables, might protect people against the consequences of H. pylori infection,” the study authors write. “On the contrary, a diet full of carbohydrates and sweets is related to a higher H. pylori infection prevalence.”
 

Why a good diet may help combat infection

The findings are consistent with other studies that have noted a higher intake of fruits and vegetables among healthy people compared with those who have H. pylori infections, the study authors write. Animal studies have also indicated that taking vitamins A, C, and E and selenium can lead to a reduction in H. pylori growth.

“Several biologically plausible reasons may explain why dietary antioxidants might be, either directly or indirectly, a protective factor against H. pylori infection,” the researchers write. “It is well-known that antioxidants, with their free radical scavenging activities, can inhibit the growth of H. pylori.”

H. pylori is urease-positive and can synthesize a large amount of urease for ammonia production to neutralize gastric acid, which allows it to colonize in the stomach epithelium, the study authors write. Vitamin C inhibits urease activity and improves the stimulation of granulocytes, macrophages, lymphocytes, and immunoglobulin production. Other nutrients, such as zinc, may inhibit the urease enzyme and prevent H. pylori adhesion to gastric tissues, they write.

“Dietary elements have previously been shown to dramatically alter pathogenic responses to H. pylori infections,” Richard Peek Jr., MD, professor of medicine and director of gastroenterology at Vanderbilt University Medical Center, Nashville, Tenn., told this news organization.

Dr. Peek, who wasn’t involved with this study, and colleagues found that iron deficiency is linked with altered bile metabolism, which can promote H. pylori–induced gastric carcinogenesis.

“The current study is important, as it suggests that shifting to a diet rich in antioxidants may be beneficial in terms of H. pylori infection,” he said.

At the same time, Dr. Peek expressed caution about generalizing the results across populations.

“Most of the persons enrolled in this study were likely infected with H. pylori as children,” he noted. “Therefore, the inverse role of antioxidant-rich diets and H. pylori infection must be interpreted with caution.”

Future studies should confirm the findings in other groups and determine whether antioxidant-rich diets limit the diseases caused by H. pylori infection, Dr. Peek added.

The study was not funded by any research center, and the authors declared no conflicts of interest. Dr. Peek reported no relevant disclosures.

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

People who eat a balanced diet with sufficient antioxidants from fruits and vegetables may face reduced risks for Heliobacter pylori infections, according to a new report.

In particular, patients with an H. pylori infection were more likely to score lower on the Dietary Antioxidant Index (DAI), which was created to consider a diet’s entire antioxidant profile.

“Available evidence indicates that diet has an important role in developing H. pylori infection. Therefore, protective dietary factors are important from a public health point of view,” Farzad Shidfar, a professor of nutrition at the Iran University of Medical Sciences, Tehran, and member of the university’s colorectal research center, and colleagues write.

“While some nutritional research has widely focused on single nutrients or foods in diet-disease relations, the overall diet could be more informative because humans typically consume a combination of nutrients and foods,” they write. “Dietary indices such as DAI are one of the approaches for this purpose.”

The study was published online in BMC Gastroenterology.
 

Measuring antioxidant intake

Previous research has indicated an inverse association between the DAI and inflammatory diseases, the study authors write, including gastric cancer, colorectal cancer, nonalcoholic fatty liver disease, and obesity. Studies have also indicated that H. pylori infection is related to deficiencies in vitamins A, C, and E, which have antioxidant properties.

In a case-control study, the research team compared the dietary intake of 148 patients with H. pylori to 302 healthy controls without infection. The patients in the H. pylori–positive group were recruited between June 2021 and November 2021 from the gastroenterology clinic at Rasoul-e-Akram Hospital in Tehran, where they were newly diagnosed with active infection and not yet under treatment.

The researchers calculated the DAI based on dietary intake information from a validated, 168-item food frequency questionnaire used in Iran. The participants were asked about their dietary intake based on the average day, week, month, and year. They also discussed serving sizes of food items, and to increase the accuracy of estimates, interviewers showed household measurements or serving sizes to confirm the measurements with participants.

The average age of the study participants was 39 years, and about 60% were women. Compared with the healthy controls, those with H. pylori were significantly older, had higher body mass index, and smoked more.

Overall, patients with H. pylori had a significantly lower intake of vitamin A, vitamin E, manganese, and selenium. Other differences in dietary intake – for vitamin C and zinc – were not significant.

The average total DAI was significantly higher in the healthy controls, at 7.67, as compared with 3.57 in the patients with H. pylori. The risk for infection decreased as continuous DAI increased.

After adjusting for several variables, the researchers found that participants with less than the median DAI values had an increased risk of developing an H. pylori infection.

“A balanced diet, especially high consumption of fruits and vegetables, might protect people against the consequences of H. pylori infection,” the study authors write. “On the contrary, a diet full of carbohydrates and sweets is related to a higher H. pylori infection prevalence.”
 

Why a good diet may help combat infection

The findings are consistent with other studies that have noted a higher intake of fruits and vegetables among healthy people compared with those who have H. pylori infections, the study authors write. Animal studies have also indicated that taking vitamins A, C, and E and selenium can lead to a reduction in H. pylori growth.

“Several biologically plausible reasons may explain why dietary antioxidants might be, either directly or indirectly, a protective factor against H. pylori infection,” the researchers write. “It is well-known that antioxidants, with their free radical scavenging activities, can inhibit the growth of H. pylori.”

H. pylori is urease-positive and can synthesize a large amount of urease for ammonia production to neutralize gastric acid, which allows it to colonize in the stomach epithelium, the study authors write. Vitamin C inhibits urease activity and improves the stimulation of granulocytes, macrophages, lymphocytes, and immunoglobulin production. Other nutrients, such as zinc, may inhibit the urease enzyme and prevent H. pylori adhesion to gastric tissues, they write.

“Dietary elements have previously been shown to dramatically alter pathogenic responses to H. pylori infections,” Richard Peek Jr., MD, professor of medicine and director of gastroenterology at Vanderbilt University Medical Center, Nashville, Tenn., told this news organization.

Dr. Peek, who wasn’t involved with this study, and colleagues found that iron deficiency is linked with altered bile metabolism, which can promote H. pylori–induced gastric carcinogenesis.

“The current study is important, as it suggests that shifting to a diet rich in antioxidants may be beneficial in terms of H. pylori infection,” he said.

At the same time, Dr. Peek expressed caution about generalizing the results across populations.

“Most of the persons enrolled in this study were likely infected with H. pylori as children,” he noted. “Therefore, the inverse role of antioxidant-rich diets and H. pylori infection must be interpreted with caution.”

Future studies should confirm the findings in other groups and determine whether antioxidant-rich diets limit the diseases caused by H. pylori infection, Dr. Peek added.

The study was not funded by any research center, and the authors declared no conflicts of interest. Dr. Peek reported no relevant disclosures.

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