Heidi Splete

Patients on immunosuppressive or immunomodulatory therapy should receive a third dose of either the Pfizer-BioNTech COVID-19 vaccine or the Moderna COVID-19 vaccine at least 28 days after the second dose of either of these two mRNA vaccines, according to updated recommendations from the American College of Rheumatology.

Mongkolchon Akesin/Getty Images

The update follows the Centers for Disease Control and Prevention’s recommendation that certain immunocompromised patients receive a third dose of an mRNA vaccine to reduce their risk of contracting COVID-19.

Individuals receiving the Pfizer vaccine must be aged 12 years and older, while those receiving the Moderna vaccine must be 18 years and older, the ACR emphasized.

“These statements were based upon a dearth of high-quality data and are not intended to replace clinical judgment,” the authors wrote. “Modifications made to treatment plans, particularly in complex rheumatic disease patients, are highly disease, patient, geography, and time specific and, therefore, must be individualized as part of a shared decision-making process.”

The task force recommended using the same mRNA vaccine booster as the patient received for their initial two-dose series when possible, but notes that either mRNA vaccine is acceptable, and recommends the mRNA vaccine for patients who have yet to receive any vaccine because of the availability of the booster. The task force emphasized that they achieved no consensus on recommending a booster mRNA vaccine to patients who received a single dose of Johnson & Johnson vaccine because the safety data are uncertain.

The updated guidance also identifies the Food and Drug Administration’s emergency use authorization in August for the use of REGEN-COV monoclonal antibody treatment for emergency postexposure prophylaxis for COVID-19 in adults and adolescents aged 12 years and older who weigh at least 40 kg and are at increased risk for severe COVID-19, which includes patients receiving immunosuppressive or immunomodulatory therapies other than hydroxychloroquine. Patients who have been exposed to an individual with COVID-19 should discuss this treatment with their health care provider as an added precaution; however, the guidance emphasized that the prophylactic treatment is not a substitute for COVID-19 vaccination.

The recommendations advise clinicians to counsel their patients to refrain from taking certain immunomodulatory or immunosuppressive medications for 1-2 weeks after booster vaccination if disease activity allows, with the exception of glucocorticoids and anticytokines such as tumor necrosis factor inhibitors and others including interleukin-17, IL-12/23, IL-23, IL-1R, IL-6R antagonists, for which the task force did not achieve a consensus recommendation.

The guidance notes that patients on rituximab or other anti-CD20 medications “should discuss the optimal timing [of the booster] with their rheumatology provider” and that some practitioners measure CD19 B cells as a tool with which to time the booster and subsequent rituximab dosing. For those who elect to dose without such information, or for whom such measurement is not available or feasible, provide the booster 2-4 weeks before next anticipated rituximab dose (e.g., at month 5.0 or 5.5 for patients on an every-6-month rituximab dosing schedule).”

There was strong consensus from the task force that health care providers “should not routinely order any lab testing (e.g., antibody tests for IgM and/or IgG to spike or nucleocapsid proteins) to assess immunity to COVID-19 post vaccination, nor to assess the need for vaccination in a yet-unvaccinated person.”

“The updated information from the ACR addresses not only booster vaccination but also other important and practical issues facing rheumatology providers and their patients related to the pandemic,” said task force chair Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, in an ACR statement announcing the updates.

“Although the guidance is issued in light of the best evidence available, the science regarding COVID-19 vaccination as it affects the practice of rheumatology is undergoing rapid evolution,” he noted. “We need direct evidence such as that from randomized trials to inform the best practices of what we can do to protect our patients from SARS-CoV-2.”

The update retains the current recommendations that rheumatology patients follow all public health guidelines regarding physical distancing and other preventive measures following vaccination, but the task force did not recommend exceeding current public health guidance. “The appropriateness for continued preventive measures (e.g., masking, physical distancing) should be discussed with patients as their rheumatology providers deem appropriate,” they wrote.

The full updated version of the ACR’s COVID-19 Vaccine Clinical Guidance for Patients with Rheumatic and Musculoskeletal Diseases will be published in Arthritis & Rheumatology. The summary was developed by the ACR COVID-19 Vaccine Clinical Guidance Task Force, which included 9 rheumatologists, 2 infectious disease specialists, and 2 public health experts with current or past employment history with the CDC.

The ACR encourages clinicians with questions or concerns to email [email protected] for support.

Patients on immunosuppressive or immunomodulatory therapy should receive a third dose of either the Pfizer-BioNTech COVID-19 vaccine or the Moderna COVID-19 vaccine at least 28 days after the second dose of either of these two mRNA vaccines, according to updated recommendations from the American College of Rheumatology.

Mongkolchon Akesin/Getty Images

The update follows the Centers for Disease Control and Prevention’s recommendation that certain immunocompromised patients receive a third dose of an mRNA vaccine to reduce their risk of contracting COVID-19.

Individuals receiving the Pfizer vaccine must be aged 12 years and older, while those receiving the Moderna vaccine must be 18 years and older, the ACR emphasized.

“These statements were based upon a dearth of high-quality data and are not intended to replace clinical judgment,” the authors wrote. “Modifications made to treatment plans, particularly in complex rheumatic disease patients, are highly disease, patient, geography, and time specific and, therefore, must be individualized as part of a shared decision-making process.”

The task force recommended using the same mRNA vaccine booster as the patient received for their initial two-dose series when possible, but notes that either mRNA vaccine is acceptable, and recommends the mRNA vaccine for patients who have yet to receive any vaccine because of the availability of the booster. The task force emphasized that they achieved no consensus on recommending a booster mRNA vaccine to patients who received a single dose of Johnson & Johnson vaccine because the safety data are uncertain.

The updated guidance also identifies the Food and Drug Administration’s emergency use authorization in August for the use of REGEN-COV monoclonal antibody treatment for emergency postexposure prophylaxis for COVID-19 in adults and adolescents aged 12 years and older who weigh at least 40 kg and are at increased risk for severe COVID-19, which includes patients receiving immunosuppressive or immunomodulatory therapies other than hydroxychloroquine. Patients who have been exposed to an individual with COVID-19 should discuss this treatment with their health care provider as an added precaution; however, the guidance emphasized that the prophylactic treatment is not a substitute for COVID-19 vaccination.

The recommendations advise clinicians to counsel their patients to refrain from taking certain immunomodulatory or immunosuppressive medications for 1-2 weeks after booster vaccination if disease activity allows, with the exception of glucocorticoids and anticytokines such as tumor necrosis factor inhibitors and others including interleukin-17, IL-12/23, IL-23, IL-1R, IL-6R antagonists, for which the task force did not achieve a consensus recommendation.

The guidance notes that patients on rituximab or other anti-CD20 medications “should discuss the optimal timing [of the booster] with their rheumatology provider” and that some practitioners measure CD19 B cells as a tool with which to time the booster and subsequent rituximab dosing. For those who elect to dose without such information, or for whom such measurement is not available or feasible, provide the booster 2-4 weeks before next anticipated rituximab dose (e.g., at month 5.0 or 5.5 for patients on an every-6-month rituximab dosing schedule).”

There was strong consensus from the task force that health care providers “should not routinely order any lab testing (e.g., antibody tests for IgM and/or IgG to spike or nucleocapsid proteins) to assess immunity to COVID-19 post vaccination, nor to assess the need for vaccination in a yet-unvaccinated person.”

“The updated information from the ACR addresses not only booster vaccination but also other important and practical issues facing rheumatology providers and their patients related to the pandemic,” said task force chair Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, in an ACR statement announcing the updates.

“Although the guidance is issued in light of the best evidence available, the science regarding COVID-19 vaccination as it affects the practice of rheumatology is undergoing rapid evolution,” he noted. “We need direct evidence such as that from randomized trials to inform the best practices of what we can do to protect our patients from SARS-CoV-2.”

The update retains the current recommendations that rheumatology patients follow all public health guidelines regarding physical distancing and other preventive measures following vaccination, but the task force did not recommend exceeding current public health guidance. “The appropriateness for continued preventive measures (e.g., masking, physical distancing) should be discussed with patients as their rheumatology providers deem appropriate,” they wrote.

The full updated version of the ACR’s COVID-19 Vaccine Clinical Guidance for Patients with Rheumatic and Musculoskeletal Diseases will be published in Arthritis & Rheumatology. The summary was developed by the ACR COVID-19 Vaccine Clinical Guidance Task Force, which included 9 rheumatologists, 2 infectious disease specialists, and 2 public health experts with current or past employment history with the CDC.

The ACR encourages clinicians with questions or concerns to email [email protected] for support.

Patients on immunosuppressive or immunomodulatory therapy should receive a third dose of either the Pfizer-BioNTech COVID-19 vaccine or the Moderna COVID-19 vaccine at least 28 days after the second dose of either of these two mRNA vaccines, according to updated recommendations from the American College of Rheumatology.

Mongkolchon Akesin/Getty Images

The update follows the Centers for Disease Control and Prevention’s recommendation that certain immunocompromised patients receive a third dose of an mRNA vaccine to reduce their risk of contracting COVID-19.

Individuals receiving the Pfizer vaccine must be aged 12 years and older, while those receiving the Moderna vaccine must be 18 years and older, the ACR emphasized.

“These statements were based upon a dearth of high-quality data and are not intended to replace clinical judgment,” the authors wrote. “Modifications made to treatment plans, particularly in complex rheumatic disease patients, are highly disease, patient, geography, and time specific and, therefore, must be individualized as part of a shared decision-making process.”

The task force recommended using the same mRNA vaccine booster as the patient received for their initial two-dose series when possible, but notes that either mRNA vaccine is acceptable, and recommends the mRNA vaccine for patients who have yet to receive any vaccine because of the availability of the booster. The task force emphasized that they achieved no consensus on recommending a booster mRNA vaccine to patients who received a single dose of Johnson & Johnson vaccine because the safety data are uncertain.

The updated guidance also identifies the Food and Drug Administration’s emergency use authorization in August for the use of REGEN-COV monoclonal antibody treatment for emergency postexposure prophylaxis for COVID-19 in adults and adolescents aged 12 years and older who weigh at least 40 kg and are at increased risk for severe COVID-19, which includes patients receiving immunosuppressive or immunomodulatory therapies other than hydroxychloroquine. Patients who have been exposed to an individual with COVID-19 should discuss this treatment with their health care provider as an added precaution; however, the guidance emphasized that the prophylactic treatment is not a substitute for COVID-19 vaccination.

The recommendations advise clinicians to counsel their patients to refrain from taking certain immunomodulatory or immunosuppressive medications for 1-2 weeks after booster vaccination if disease activity allows, with the exception of glucocorticoids and anticytokines such as tumor necrosis factor inhibitors and others including interleukin-17, IL-12/23, IL-23, IL-1R, IL-6R antagonists, for which the task force did not achieve a consensus recommendation.

The guidance notes that patients on rituximab or other anti-CD20 medications “should discuss the optimal timing [of the booster] with their rheumatology provider” and that some practitioners measure CD19 B cells as a tool with which to time the booster and subsequent rituximab dosing. For those who elect to dose without such information, or for whom such measurement is not available or feasible, provide the booster 2-4 weeks before next anticipated rituximab dose (e.g., at month 5.0 or 5.5 for patients on an every-6-month rituximab dosing schedule).”

There was strong consensus from the task force that health care providers “should not routinely order any lab testing (e.g., antibody tests for IgM and/or IgG to spike or nucleocapsid proteins) to assess immunity to COVID-19 post vaccination, nor to assess the need for vaccination in a yet-unvaccinated person.”

“The updated information from the ACR addresses not only booster vaccination but also other important and practical issues facing rheumatology providers and their patients related to the pandemic,” said task force chair Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, in an ACR statement announcing the updates.

“Although the guidance is issued in light of the best evidence available, the science regarding COVID-19 vaccination as it affects the practice of rheumatology is undergoing rapid evolution,” he noted. “We need direct evidence such as that from randomized trials to inform the best practices of what we can do to protect our patients from SARS-CoV-2.”

The update retains the current recommendations that rheumatology patients follow all public health guidelines regarding physical distancing and other preventive measures following vaccination, but the task force did not recommend exceeding current public health guidance. “The appropriateness for continued preventive measures (e.g., masking, physical distancing) should be discussed with patients as their rheumatology providers deem appropriate,” they wrote.

The full updated version of the ACR’s COVID-19 Vaccine Clinical Guidance for Patients with Rheumatic and Musculoskeletal Diseases will be published in Arthritis & Rheumatology. The summary was developed by the ACR COVID-19 Vaccine Clinical Guidance Task Force, which included 9 rheumatologists, 2 infectious disease specialists, and 2 public health experts with current or past employment history with the CDC.

The ACR encourages clinicians with questions or concerns to email [email protected] for support.

Death from COVID-19 was not more likely among patients with inflammatory bowel disease (IBD) who had COVID-19 who developed new GI symptoms after becoming infected, according to international registry data from nearly 3,000 adults.

Although GI symptoms may arise in the general population of COVID-19 patients, data on the association between GI symptoms and COVID-19 in patients with IBD are limited, as are data on the association of GI symptoms and COVID-19 outcomes in this population, Ryan C. Ungaro, MD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues wrote.

In a study published in Inflammatory Bowel Diseases, the researchers identified 2,917 adults with IBD who developed COVID-19 using the Surveillance Epidemiology of Coronavirus Under Research Exclusion in Inflammatory Bowel Disease (SECURE-IBD) database, a global registry created to understand COVID-19 outcomes in IBD patients.

The researchers recorded all new GI symptoms experienced by the patients while they were infected with COVID-19. Overall, 764 (26.2%) experienced new GI symptoms and 2,153 did not. The most common symptom was diarrhea, reported by 80% of the patients, followed by abdominal pain in 34%. Nausea and vomiting were reported by 24% and 12%, respectively, of all patients.

The average age of the patients was 43 years for those with no new GI symptoms and 40 for those without new GI symptoms; overall, approximately half were women and approximately three-quarters were White. Overall, 50% of those with new GI symptoms were in remission, as was the case for 58.4% of those without.

IBD patients who developed new GI symptoms were significantly more likely to be women, of Asian race, older, or have at least one comorbidity.

The researchers found no difference in new GI symptoms in patients with Crohn’s disease and ulcerative colitis. “Patients on any medication – but in particular [tumor necrosis factor] antagonist monotherapy – were less likely to report new GI symptoms.” they wrote.

Although IBD patients with new GI symptoms were significantly more likely than were those without new GI symptoms to be hospitalized for COVID-19 in bivariate analyses (31.4% vs. 19.2%; P < .001), they were not more likely to need a ventilator or intensive care (5.8% vs. 4.6%; P < .18). In a multivariate analysis, IBD patients with new GI symptoms had no greater risk of death from COVID-19 than did those without new GI symptoms (adjusted odds ratio, 0.72; 95% confidence interval, 0.38-1.36).

The new-onset GI symptoms common to IBD patients with COVID-19 are not likely caused by underlying disease activity, given the number of patients in remission who reported new GI symptoms, the researchers wrote.

The study findings were limited by several factors including the retrospective design, potential reporting bias, and reliance on physician global assessment for disease assessment, the researchers noted. However, the results were strengthened by the large sample size, by the ability to assess GI symptoms before and after COVID-19, and by the evaluation of GI symptoms and COVID-19 outcomes.

“In summary, new GI symptoms are common in IBD patients with COVID-19 and are not associated with an increased risk of death due to COVID-19,” the researchers concluded. “Our findings suggest that an increase in GI symptoms in IBD patients should prompt consideration of a COVID-19 diagnosis.”
 

Data to guide clinical care

“There are several potential causes for common GI symptoms, such as diarrhea and abdominal pain, among patients with IBD,” Shirley Cohen-Mekelburg, MD, of the University of Michigan, Ann Arbor, said in an interview. “These can be the initial presentation of an IBD flare, a noninflammatory cause such as irritable bowel syndrome, small intestinal bacterial overgrowth, or an infection such as Clostridioides difficile or SARS-CoV-2. Each of these diagnoses require different treatments. An IBD flare may require escalation of immunosuppressive medications such as biologics or corticosteroids, which can cause harm in the context of an untreated infection. Therefore, any guidance that will increase health care providers’ awareness of the possible causes of similar GI symptoms is important in caring for our patients with IBD. This is especially true in context of a newer entity such as COVID-19 with which we are overall less familiar.”

Dr. Cohen-Meckelburg said the lack of association between GI symptoms and death in IBD is reassuring. “It is interesting to note that GI symptoms, and particularly new diarrhea, were very common among patients with IBD and COVID-19,” she added.

“Every study has its limitations, which need to be considered in interpreting findings,” Dr. Cohen-Meckelburg noted . “SECURE-IBD has provided great insight into COVID-19 infections among patients with IBD. However, the registry relies on individuals reporting cases, so there is the potential for underreporting, particularly with less symptomatic or subclinical cases.”

“Health care providers who treat patients with IBD should have a high-index of suspicion for SARS-CoV-2 infections when patients with IBD present with GI symptoms,” said Dr. Cohen-Meckelburg. “The data from the current study may help us to consider standard testing to rule out COVID-19 as an alternative diagnosis when considering whether to treat patients with IBD who develop new GI symptoms for an IBD flare. This would be similar to how we currently test for C. difficile and other enteric infections before treating IBD flares.

“This approach – considering the possibility of COVID-19 in the context of new GI symptoms – is consistent with the AGA’s published guidelines and best practices,” said David Leiman, MD, MSHP, of Duke University, Durham, N.C., and Chair of the AGA’s Quality Committee. “Clinicians should also be aware of the possibility for variation in implementation of this approach, with some patients potentially at risk for disparate testing practices.” As outlined by the AGA’s Quality Committee, tracking adherence to this clinical approach through ongoing quality improvement may limit the development of such gaps in care.

The study was supported in part by the Helmsley Charitable Trust with additional funding provided by Pfizer, Takeda, Janssen, AbbVie, Lilly, Genentech, Boehringer Ingelheim, Bristol-Myers Squibb, Celtrion, and Arenapharm. Lead author Dr. Ungaro disclosed serving as an advisory board member or consultant for AbbVie, Bristol-Myers Squibb, Janssen, Eli Lilly, Pfizer, and Takeda and research support from AbbVie, Boehringer Ingelheim, and Pfizer. Other coauthors disclosed similar relationships with other pharmaceutical companies. Dr. Cohen-Mekelburg and Dr. Leiman had no financial conflicts to disclose.

Death from COVID-19 was not more likely among patients with inflammatory bowel disease (IBD) who had COVID-19 who developed new GI symptoms after becoming infected, according to international registry data from nearly 3,000 adults.

Although GI symptoms may arise in the general population of COVID-19 patients, data on the association between GI symptoms and COVID-19 in patients with IBD are limited, as are data on the association of GI symptoms and COVID-19 outcomes in this population, Ryan C. Ungaro, MD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues wrote.

In a study published in Inflammatory Bowel Diseases, the researchers identified 2,917 adults with IBD who developed COVID-19 using the Surveillance Epidemiology of Coronavirus Under Research Exclusion in Inflammatory Bowel Disease (SECURE-IBD) database, a global registry created to understand COVID-19 outcomes in IBD patients.

The researchers recorded all new GI symptoms experienced by the patients while they were infected with COVID-19. Overall, 764 (26.2%) experienced new GI symptoms and 2,153 did not. The most common symptom was diarrhea, reported by 80% of the patients, followed by abdominal pain in 34%. Nausea and vomiting were reported by 24% and 12%, respectively, of all patients.

The average age of the patients was 43 years for those with no new GI symptoms and 40 for those without new GI symptoms; overall, approximately half were women and approximately three-quarters were White. Overall, 50% of those with new GI symptoms were in remission, as was the case for 58.4% of those without.

IBD patients who developed new GI symptoms were significantly more likely to be women, of Asian race, older, or have at least one comorbidity.

The researchers found no difference in new GI symptoms in patients with Crohn’s disease and ulcerative colitis. “Patients on any medication – but in particular [tumor necrosis factor] antagonist monotherapy – were less likely to report new GI symptoms.” they wrote.

Although IBD patients with new GI symptoms were significantly more likely than were those without new GI symptoms to be hospitalized for COVID-19 in bivariate analyses (31.4% vs. 19.2%; P < .001), they were not more likely to need a ventilator or intensive care (5.8% vs. 4.6%; P < .18). In a multivariate analysis, IBD patients with new GI symptoms had no greater risk of death from COVID-19 than did those without new GI symptoms (adjusted odds ratio, 0.72; 95% confidence interval, 0.38-1.36).

The new-onset GI symptoms common to IBD patients with COVID-19 are not likely caused by underlying disease activity, given the number of patients in remission who reported new GI symptoms, the researchers wrote.

The study findings were limited by several factors including the retrospective design, potential reporting bias, and reliance on physician global assessment for disease assessment, the researchers noted. However, the results were strengthened by the large sample size, by the ability to assess GI symptoms before and after COVID-19, and by the evaluation of GI symptoms and COVID-19 outcomes.

“In summary, new GI symptoms are common in IBD patients with COVID-19 and are not associated with an increased risk of death due to COVID-19,” the researchers concluded. “Our findings suggest that an increase in GI symptoms in IBD patients should prompt consideration of a COVID-19 diagnosis.”
 

Data to guide clinical care

“There are several potential causes for common GI symptoms, such as diarrhea and abdominal pain, among patients with IBD,” Shirley Cohen-Mekelburg, MD, of the University of Michigan, Ann Arbor, said in an interview. “These can be the initial presentation of an IBD flare, a noninflammatory cause such as irritable bowel syndrome, small intestinal bacterial overgrowth, or an infection such as Clostridioides difficile or SARS-CoV-2. Each of these diagnoses require different treatments. An IBD flare may require escalation of immunosuppressive medications such as biologics or corticosteroids, which can cause harm in the context of an untreated infection. Therefore, any guidance that will increase health care providers’ awareness of the possible causes of similar GI symptoms is important in caring for our patients with IBD. This is especially true in context of a newer entity such as COVID-19 with which we are overall less familiar.”

Dr. Cohen-Meckelburg said the lack of association between GI symptoms and death in IBD is reassuring. “It is interesting to note that GI symptoms, and particularly new diarrhea, were very common among patients with IBD and COVID-19,” she added.

“Every study has its limitations, which need to be considered in interpreting findings,” Dr. Cohen-Meckelburg noted . “SECURE-IBD has provided great insight into COVID-19 infections among patients with IBD. However, the registry relies on individuals reporting cases, so there is the potential for underreporting, particularly with less symptomatic or subclinical cases.”

“Health care providers who treat patients with IBD should have a high-index of suspicion for SARS-CoV-2 infections when patients with IBD present with GI symptoms,” said Dr. Cohen-Meckelburg. “The data from the current study may help us to consider standard testing to rule out COVID-19 as an alternative diagnosis when considering whether to treat patients with IBD who develop new GI symptoms for an IBD flare. This would be similar to how we currently test for C. difficile and other enteric infections before treating IBD flares.

“This approach – considering the possibility of COVID-19 in the context of new GI symptoms – is consistent with the AGA’s published guidelines and best practices,” said David Leiman, MD, MSHP, of Duke University, Durham, N.C., and Chair of the AGA’s Quality Committee. “Clinicians should also be aware of the possibility for variation in implementation of this approach, with some patients potentially at risk for disparate testing practices.” As outlined by the AGA’s Quality Committee, tracking adherence to this clinical approach through ongoing quality improvement may limit the development of such gaps in care.

The study was supported in part by the Helmsley Charitable Trust with additional funding provided by Pfizer, Takeda, Janssen, AbbVie, Lilly, Genentech, Boehringer Ingelheim, Bristol-Myers Squibb, Celtrion, and Arenapharm. Lead author Dr. Ungaro disclosed serving as an advisory board member or consultant for AbbVie, Bristol-Myers Squibb, Janssen, Eli Lilly, Pfizer, and Takeda and research support from AbbVie, Boehringer Ingelheim, and Pfizer. Other coauthors disclosed similar relationships with other pharmaceutical companies. Dr. Cohen-Mekelburg and Dr. Leiman had no financial conflicts to disclose.

Death from COVID-19 was not more likely among patients with inflammatory bowel disease (IBD) who had COVID-19 who developed new GI symptoms after becoming infected, according to international registry data from nearly 3,000 adults.

Although GI symptoms may arise in the general population of COVID-19 patients, data on the association between GI symptoms and COVID-19 in patients with IBD are limited, as are data on the association of GI symptoms and COVID-19 outcomes in this population, Ryan C. Ungaro, MD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues wrote.

In a study published in Inflammatory Bowel Diseases, the researchers identified 2,917 adults with IBD who developed COVID-19 using the Surveillance Epidemiology of Coronavirus Under Research Exclusion in Inflammatory Bowel Disease (SECURE-IBD) database, a global registry created to understand COVID-19 outcomes in IBD patients.

The researchers recorded all new GI symptoms experienced by the patients while they were infected with COVID-19. Overall, 764 (26.2%) experienced new GI symptoms and 2,153 did not. The most common symptom was diarrhea, reported by 80% of the patients, followed by abdominal pain in 34%. Nausea and vomiting were reported by 24% and 12%, respectively, of all patients.

The average age of the patients was 43 years for those with no new GI symptoms and 40 for those without new GI symptoms; overall, approximately half were women and approximately three-quarters were White. Overall, 50% of those with new GI symptoms were in remission, as was the case for 58.4% of those without.

IBD patients who developed new GI symptoms were significantly more likely to be women, of Asian race, older, or have at least one comorbidity.

The researchers found no difference in new GI symptoms in patients with Crohn’s disease and ulcerative colitis. “Patients on any medication – but in particular [tumor necrosis factor] antagonist monotherapy – were less likely to report new GI symptoms.” they wrote.

Although IBD patients with new GI symptoms were significantly more likely than were those without new GI symptoms to be hospitalized for COVID-19 in bivariate analyses (31.4% vs. 19.2%; P < .001), they were not more likely to need a ventilator or intensive care (5.8% vs. 4.6%; P < .18). In a multivariate analysis, IBD patients with new GI symptoms had no greater risk of death from COVID-19 than did those without new GI symptoms (adjusted odds ratio, 0.72; 95% confidence interval, 0.38-1.36).

The new-onset GI symptoms common to IBD patients with COVID-19 are not likely caused by underlying disease activity, given the number of patients in remission who reported new GI symptoms, the researchers wrote.

The study findings were limited by several factors including the retrospective design, potential reporting bias, and reliance on physician global assessment for disease assessment, the researchers noted. However, the results were strengthened by the large sample size, by the ability to assess GI symptoms before and after COVID-19, and by the evaluation of GI symptoms and COVID-19 outcomes.

“In summary, new GI symptoms are common in IBD patients with COVID-19 and are not associated with an increased risk of death due to COVID-19,” the researchers concluded. “Our findings suggest that an increase in GI symptoms in IBD patients should prompt consideration of a COVID-19 diagnosis.”
 

Data to guide clinical care

“There are several potential causes for common GI symptoms, such as diarrhea and abdominal pain, among patients with IBD,” Shirley Cohen-Mekelburg, MD, of the University of Michigan, Ann Arbor, said in an interview. “These can be the initial presentation of an IBD flare, a noninflammatory cause such as irritable bowel syndrome, small intestinal bacterial overgrowth, or an infection such as Clostridioides difficile or SARS-CoV-2. Each of these diagnoses require different treatments. An IBD flare may require escalation of immunosuppressive medications such as biologics or corticosteroids, which can cause harm in the context of an untreated infection. Therefore, any guidance that will increase health care providers’ awareness of the possible causes of similar GI symptoms is important in caring for our patients with IBD. This is especially true in context of a newer entity such as COVID-19 with which we are overall less familiar.”

Dr. Cohen-Meckelburg said the lack of association between GI symptoms and death in IBD is reassuring. “It is interesting to note that GI symptoms, and particularly new diarrhea, were very common among patients with IBD and COVID-19,” she added.

“Every study has its limitations, which need to be considered in interpreting findings,” Dr. Cohen-Meckelburg noted . “SECURE-IBD has provided great insight into COVID-19 infections among patients with IBD. However, the registry relies on individuals reporting cases, so there is the potential for underreporting, particularly with less symptomatic or subclinical cases.”

“Health care providers who treat patients with IBD should have a high-index of suspicion for SARS-CoV-2 infections when patients with IBD present with GI symptoms,” said Dr. Cohen-Meckelburg. “The data from the current study may help us to consider standard testing to rule out COVID-19 as an alternative diagnosis when considering whether to treat patients with IBD who develop new GI symptoms for an IBD flare. This would be similar to how we currently test for C. difficile and other enteric infections before treating IBD flares.

“This approach – considering the possibility of COVID-19 in the context of new GI symptoms – is consistent with the AGA’s published guidelines and best practices,” said David Leiman, MD, MSHP, of Duke University, Durham, N.C., and Chair of the AGA’s Quality Committee. “Clinicians should also be aware of the possibility for variation in implementation of this approach, with some patients potentially at risk for disparate testing practices.” As outlined by the AGA’s Quality Committee, tracking adherence to this clinical approach through ongoing quality improvement may limit the development of such gaps in care.

The study was supported in part by the Helmsley Charitable Trust with additional funding provided by Pfizer, Takeda, Janssen, AbbVie, Lilly, Genentech, Boehringer Ingelheim, Bristol-Myers Squibb, Celtrion, and Arenapharm. Lead author Dr. Ungaro disclosed serving as an advisory board member or consultant for AbbVie, Bristol-Myers Squibb, Janssen, Eli Lilly, Pfizer, and Takeda and research support from AbbVie, Boehringer Ingelheim, and Pfizer. Other coauthors disclosed similar relationships with other pharmaceutical companies. Dr. Cohen-Mekelburg and Dr. Leiman had no financial conflicts to disclose.

Death from COVID-19 was not more likely among patients with inflammatory bowel disease (IBD) who had COVID-19 who developed new GI symptoms after becoming infected, according to international registry data from nearly 3,000 adults.

Although GI symptoms may arise in the general population of COVID-19 patients, data on the association between GI symptoms and COVID-19 in patients with IBD are limited, as are data on the association of GI symptoms and COVID-19 outcomes in this population, Ryan C. Ungaro, MD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues wrote.

In a study published in Inflammatory Bowel Diseases, the researchers identified 2,917 adults with IBD who developed COVID-19 using the Surveillance Epidemiology of Coronavirus Under Research Exclusion in Inflammatory Bowel Disease (SECURE-IBD) database, a global registry created to understand COVID-19 outcomes in IBD patients.

The researchers recorded all new GI symptoms experienced by the patients while they were infected with COVID-19. Overall, 764 (26.2%) experienced new GI symptoms and 2,153 did not. The most common symptom was diarrhea, reported by 80% of the patients, followed by abdominal pain in 34%. Nausea and vomiting were reported by 24% and 12%, respectively, of all patients.

The average age of the patients was 43 years for those with no new GI symptoms and 40 for those without new GI symptoms; overall, approximately half were women and approximately three-quarters were White. Overall, 50% of those with new GI symptoms were in remission, as was the case for 58.4% of those without.

IBD patients who developed new GI symptoms were significantly more likely to be women, of Asian race, older, or have at least one comorbidity.

The researchers found no difference in new GI symptoms in patients with Crohn’s disease and ulcerative colitis. “Patients on any medication – but in particular [tumor necrosis factor] antagonist monotherapy – were less likely to report new GI symptoms.” they wrote.

Although IBD patients with new GI symptoms were significantly more likely than were those without new GI symptoms to be hospitalized for COVID-19 in bivariate analyses (31.4% vs. 19.2%; P < .001), they were not more likely to need a ventilator or intensive care (5.8% vs. 4.6%; P < .18). In a multivariate analysis, IBD patients with new GI symptoms had no greater risk of death from COVID-19 than did those without new GI symptoms (adjusted odds ratio, 0.72; 95% confidence interval, 0.38-1.36).

The new-onset GI symptoms common to IBD patients with COVID-19 are not likely caused by underlying disease activity, given the number of patients in remission who reported new GI symptoms, the researchers wrote.

The study findings were limited by several factors including the retrospective design, potential reporting bias, and reliance on physician global assessment for disease assessment, the researchers noted. However, the results were strengthened by the large sample size, by the ability to assess GI symptoms before and after COVID-19, and by the evaluation of GI symptoms and COVID-19 outcomes.

“In summary, new GI symptoms are common in IBD patients with COVID-19 and are not associated with an increased risk of death due to COVID-19,” the researchers concluded. “Our findings suggest that an increase in GI symptoms in IBD patients should prompt consideration of a COVID-19 diagnosis.”
 

Data to guide clinical care

“There are several potential causes for common GI symptoms, such as diarrhea and abdominal pain, among patients with IBD,” Shirley Cohen-Mekelburg, MD, of the University of Michigan, Ann Arbor, said in an interview. “These can be the initial presentation of an IBD flare, a noninflammatory cause such as irritable bowel syndrome, small intestinal bacterial overgrowth, or an infection such as Clostridioides difficile or SARS-CoV-2. Each of these diagnoses require different treatments. An IBD flare may require escalation of immunosuppressive medications such as biologics or corticosteroids, which can cause harm in the context of an untreated infection. Therefore, any guidance that will increase health care providers’ awareness of the possible causes of similar GI symptoms is important in caring for our patients with IBD. This is especially true in context of a newer entity such as COVID-19 with which we are overall less familiar.”

Dr. Cohen-Meckelburg said the lack of association between GI symptoms and death in IBD is reassuring. “It is interesting to note that GI symptoms, and particularly new diarrhea, were very common among patients with IBD and COVID-19.

“Health care providers who treat patients with IBD should have a high-index of suspicion for SARS-CoV-2 infections when patients with IBD present with GI symptoms,” said Dr. Cohen-Meckelburg. “The data from the current study may help us to consider standard testing to rule out COVID-19 as an alternative diagnosis when considering whether to treat patients with IBD who develop new GI symptoms for an IBD flare. This would be similar to how we currently test for C. difficile and other enteric infections before treating IBD flares.

“Every study has its limitations, which need to be considered in interpreting findings,” Dr. Cohen-Meckelburg noted . “SECURE-IBD has provided great insight into COVID-19 infections among patients with IBD. However, the registry relies on individuals reporting cases, so there is the potential for underreporting, particularly with less symptomatic or subclinical cases.”

The study was supported in part by the Helmsley Charitable Trust with additional funding provided by Pfizer, Takeda, Janssen, AbbVie, Lilly, Genentech, Boehringer Ingelheim, Bristol-Myers Squibb, Celtrion, and Arenapharm. Lead author Dr. Ungaro disclosed serving as an advisory board member or consultant for AbbVie, Bristol-Myers Squibb, Janssen, Eli Lilly, Pfizer, and Takeda and research support from AbbVie, Boehringer Ingelheim, and Pfizer. Other coauthors disclosed similar relationships with other pharmaceutical companies. Dr. Cohen-Mekelburg had no financial conflicts to disclose.

Death from COVID-19 was not more likely among patients with inflammatory bowel disease (IBD) who had COVID-19 who developed new GI symptoms after becoming infected, according to international registry data from nearly 3,000 adults.

Although GI symptoms may arise in the general population of COVID-19 patients, data on the association between GI symptoms and COVID-19 in patients with IBD are limited, as are data on the association of GI symptoms and COVID-19 outcomes in this population, Ryan C. Ungaro, MD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues wrote.

In a study published in Inflammatory Bowel Diseases, the researchers identified 2,917 adults with IBD who developed COVID-19 using the Surveillance Epidemiology of Coronavirus Under Research Exclusion in Inflammatory Bowel Disease (SECURE-IBD) database, a global registry created to understand COVID-19 outcomes in IBD patients.

The researchers recorded all new GI symptoms experienced by the patients while they were infected with COVID-19. Overall, 764 (26.2%) experienced new GI symptoms and 2,153 did not. The most common symptom was diarrhea, reported by 80% of the patients, followed by abdominal pain in 34%. Nausea and vomiting were reported by 24% and 12%, respectively, of all patients.

The average age of the patients was 43 years for those with no new GI symptoms and 40 for those without new GI symptoms; overall, approximately half were women and approximately three-quarters were White. Overall, 50% of those with new GI symptoms were in remission, as was the case for 58.4% of those without.

IBD patients who developed new GI symptoms were significantly more likely to be women, of Asian race, older, or have at least one comorbidity.

The researchers found no difference in new GI symptoms in patients with Crohn’s disease and ulcerative colitis. “Patients on any medication – but in particular [tumor necrosis factor] antagonist monotherapy – were less likely to report new GI symptoms.” they wrote.

Although IBD patients with new GI symptoms were significantly more likely than were those without new GI symptoms to be hospitalized for COVID-19 in bivariate analyses (31.4% vs. 19.2%; P < .001), they were not more likely to need a ventilator or intensive care (5.8% vs. 4.6%; P < .18). In a multivariate analysis, IBD patients with new GI symptoms had no greater risk of death from COVID-19 than did those without new GI symptoms (adjusted odds ratio, 0.72; 95% confidence interval, 0.38-1.36).

The new-onset GI symptoms common to IBD patients with COVID-19 are not likely caused by underlying disease activity, given the number of patients in remission who reported new GI symptoms, the researchers wrote.

The study findings were limited by several factors including the retrospective design, potential reporting bias, and reliance on physician global assessment for disease assessment, the researchers noted. However, the results were strengthened by the large sample size, by the ability to assess GI symptoms before and after COVID-19, and by the evaluation of GI symptoms and COVID-19 outcomes.

“In summary, new GI symptoms are common in IBD patients with COVID-19 and are not associated with an increased risk of death due to COVID-19,” the researchers concluded. “Our findings suggest that an increase in GI symptoms in IBD patients should prompt consideration of a COVID-19 diagnosis.”
 

Data to guide clinical care

“There are several potential causes for common GI symptoms, such as diarrhea and abdominal pain, among patients with IBD,” Shirley Cohen-Mekelburg, MD, of the University of Michigan, Ann Arbor, said in an interview. “These can be the initial presentation of an IBD flare, a noninflammatory cause such as irritable bowel syndrome, small intestinal bacterial overgrowth, or an infection such as Clostridioides difficile or SARS-CoV-2. Each of these diagnoses require different treatments. An IBD flare may require escalation of immunosuppressive medications such as biologics or corticosteroids, which can cause harm in the context of an untreated infection. Therefore, any guidance that will increase health care providers’ awareness of the possible causes of similar GI symptoms is important in caring for our patients with IBD. This is especially true in context of a newer entity such as COVID-19 with which we are overall less familiar.”

Dr. Cohen-Meckelburg said the lack of association between GI symptoms and death in IBD is reassuring. “It is interesting to note that GI symptoms, and particularly new diarrhea, were very common among patients with IBD and COVID-19.

“Health care providers who treat patients with IBD should have a high-index of suspicion for SARS-CoV-2 infections when patients with IBD present with GI symptoms,” said Dr. Cohen-Meckelburg. “The data from the current study may help us to consider standard testing to rule out COVID-19 as an alternative diagnosis when considering whether to treat patients with IBD who develop new GI symptoms for an IBD flare. This would be similar to how we currently test for C. difficile and other enteric infections before treating IBD flares.

“Every study has its limitations, which need to be considered in interpreting findings,” Dr. Cohen-Meckelburg noted . “SECURE-IBD has provided great insight into COVID-19 infections among patients with IBD. However, the registry relies on individuals reporting cases, so there is the potential for underreporting, particularly with less symptomatic or subclinical cases.”

The study was supported in part by the Helmsley Charitable Trust with additional funding provided by Pfizer, Takeda, Janssen, AbbVie, Lilly, Genentech, Boehringer Ingelheim, Bristol-Myers Squibb, Celtrion, and Arenapharm. Lead author Dr. Ungaro disclosed serving as an advisory board member or consultant for AbbVie, Bristol-Myers Squibb, Janssen, Eli Lilly, Pfizer, and Takeda and research support from AbbVie, Boehringer Ingelheim, and Pfizer. Other coauthors disclosed similar relationships with other pharmaceutical companies. Dr. Cohen-Mekelburg had no financial conflicts to disclose.

Death from COVID-19 was not more likely among patients with inflammatory bowel disease (IBD) who had COVID-19 who developed new GI symptoms after becoming infected, according to international registry data from nearly 3,000 adults.

Although GI symptoms may arise in the general population of COVID-19 patients, data on the association between GI symptoms and COVID-19 in patients with IBD are limited, as are data on the association of GI symptoms and COVID-19 outcomes in this population, Ryan C. Ungaro, MD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues wrote.

In a study published in Inflammatory Bowel Diseases, the researchers identified 2,917 adults with IBD who developed COVID-19 using the Surveillance Epidemiology of Coronavirus Under Research Exclusion in Inflammatory Bowel Disease (SECURE-IBD) database, a global registry created to understand COVID-19 outcomes in IBD patients.

The researchers recorded all new GI symptoms experienced by the patients while they were infected with COVID-19. Overall, 764 (26.2%) experienced new GI symptoms and 2,153 did not. The most common symptom was diarrhea, reported by 80% of the patients, followed by abdominal pain in 34%. Nausea and vomiting were reported by 24% and 12%, respectively, of all patients.

The average age of the patients was 43 years for those with no new GI symptoms and 40 for those without new GI symptoms; overall, approximately half were women and approximately three-quarters were White. Overall, 50% of those with new GI symptoms were in remission, as was the case for 58.4% of those without.

IBD patients who developed new GI symptoms were significantly more likely to be women, of Asian race, older, or have at least one comorbidity.

The researchers found no difference in new GI symptoms in patients with Crohn’s disease and ulcerative colitis. “Patients on any medication – but in particular [tumor necrosis factor] antagonist monotherapy – were less likely to report new GI symptoms.” they wrote.

Although IBD patients with new GI symptoms were significantly more likely than were those without new GI symptoms to be hospitalized for COVID-19 in bivariate analyses (31.4% vs. 19.2%; P < .001), they were not more likely to need a ventilator or intensive care (5.8% vs. 4.6%; P < .18). In a multivariate analysis, IBD patients with new GI symptoms had no greater risk of death from COVID-19 than did those without new GI symptoms (adjusted odds ratio, 0.72; 95% confidence interval, 0.38-1.36).

The new-onset GI symptoms common to IBD patients with COVID-19 are not likely caused by underlying disease activity, given the number of patients in remission who reported new GI symptoms, the researchers wrote.

The study findings were limited by several factors including the retrospective design, potential reporting bias, and reliance on physician global assessment for disease assessment, the researchers noted. However, the results were strengthened by the large sample size, by the ability to assess GI symptoms before and after COVID-19, and by the evaluation of GI symptoms and COVID-19 outcomes.

“In summary, new GI symptoms are common in IBD patients with COVID-19 and are not associated with an increased risk of death due to COVID-19,” the researchers concluded. “Our findings suggest that an increase in GI symptoms in IBD patients should prompt consideration of a COVID-19 diagnosis.”
 

Data to guide clinical care

“There are several potential causes for common GI symptoms, such as diarrhea and abdominal pain, among patients with IBD,” Shirley Cohen-Mekelburg, MD, of the University of Michigan, Ann Arbor, said in an interview. “These can be the initial presentation of an IBD flare, a noninflammatory cause such as irritable bowel syndrome, small intestinal bacterial overgrowth, or an infection such as Clostridioides difficile or SARS-CoV-2. Each of these diagnoses require different treatments. An IBD flare may require escalation of immunosuppressive medications such as biologics or corticosteroids, which can cause harm in the context of an untreated infection. Therefore, any guidance that will increase health care providers’ awareness of the possible causes of similar GI symptoms is important in caring for our patients with IBD. This is especially true in context of a newer entity such as COVID-19 with which we are overall less familiar.”

Dr. Cohen-Meckelburg said the lack of association between GI symptoms and death in IBD is reassuring. “It is interesting to note that GI symptoms, and particularly new diarrhea, were very common among patients with IBD and COVID-19.

“Health care providers who treat patients with IBD should have a high-index of suspicion for SARS-CoV-2 infections when patients with IBD present with GI symptoms,” said Dr. Cohen-Meckelburg. “The data from the current study may help us to consider standard testing to rule out COVID-19 as an alternative diagnosis when considering whether to treat patients with IBD who develop new GI symptoms for an IBD flare. This would be similar to how we currently test for C. difficile and other enteric infections before treating IBD flares.

“Every study has its limitations, which need to be considered in interpreting findings,” Dr. Cohen-Meckelburg noted . “SECURE-IBD has provided great insight into COVID-19 infections among patients with IBD. However, the registry relies on individuals reporting cases, so there is the potential for underreporting, particularly with less symptomatic or subclinical cases.”

The study was supported in part by the Helmsley Charitable Trust with additional funding provided by Pfizer, Takeda, Janssen, AbbVie, Lilly, Genentech, Boehringer Ingelheim, Bristol-Myers Squibb, Celtrion, and Arenapharm. Lead author Dr. Ungaro disclosed serving as an advisory board member or consultant for AbbVie, Bristol-Myers Squibb, Janssen, Eli Lilly, Pfizer, and Takeda and research support from AbbVie, Boehringer Ingelheim, and Pfizer. Other coauthors disclosed similar relationships with other pharmaceutical companies. Dr. Cohen-Mekelburg had no financial conflicts to disclose.

Most instances of stent misdeployment in cases of endoscopic ultrasound–guided gastroenterostomy (EUS-GE) can be managed endoscopically, based on data from 16 tertiary care centers in the United States and Europe.

EUS-GE provides a viable alternative to traditional surgical gastroenterostomy and stent placement for patients with gastric outlet obstruction (GOO), but the potential for stent misdeployment has limited adoption of the procedure because it remains the most common cause of technical failures and adverse events, Bachir Ghandour, MD, of Johns Hopkins University, Baltimore, and colleagues wrote.

However, data on outcomes and management of stent misdeployment during EUS-GE are limited, and the researchers hypothesized that most stent misdeployments could be managed endoscopically.

In a retrospective study published in Gastrointestinal Endoscopy, the researchers reviewed data from 467 EUS-GE procedures performed for gastric outlet obstruction between March 2015 and December 2020 at eight centers in the United States and eight in Europe. The primary outcome was the rate and severity of stent misdeployment.

Stent misdeployment occurred in 46 patients (9.9%). Of these, 73.2% occurred during the operators’ first 13 cases.

The researchers created a classification system of stent misdeployment according to type, depending on which flange was misdeployed.

Type I was the most common, and occurred in 29 patients; this type was defined as “the deployment of the distal flange in the peritoneum and proximal flange in the stomach without evidence of a resulting enterotomy”; type II (14 patients) was defined as “the deployment of the distal flange in the peritoneum and proximal flange in the stomach despite an enterotomy (i.e., visual confirmation of stent having penetrated targeted small bowel, under EUS or fluoroscopy, but migrated out on deployment)”; type III (1 patient) was defined as “the deployment of the distal flange in the small bowel and proximal flange in the peritoneum”; and type IV (2 patients) was defined as “the deployment of the distal flange in the colon and proximal flange in the stomach resulting in a gastrocolic anastomosis,” the researchers wrote.

The researchers also classified the stent misdeployment in terms of severity as mild (28 patients), moderate (11 patients), severe (6 cases) or fatal (1 case) based on the American Society for Gastrointestinal Endoscopy lexicon.

Overall, type I was significantly more likely to be mild in severity, compared with type II (75.9% vs. 42.9%; P = .04), although the rate of surgical repair was similar between these two types (10.3% vs. 7.1%). Rates of ICU admission were approximately 7% in patients with type I and type II stent misdeployments, and the median postprocedural stay was 4 days for these two groups.

Same-session salvage management of GOO was achieved by EUS/endoscopic-GE in 24 patients, duodenal stent placement in 6 patients, duodenal dilation in 1 patient, and gastroenterostomy with natural orifice transluminal endoscopic surgery in 3 patients. Of the remaining 12 patients, GOO was managed with subsequent EUS-GE in 6 patients and surgical GI in 6 patients.

The study findings were limited by several factors including the retrospective design and inclusion of a time period that encompassed changes and improvements in the EUS-GE, the researchers noted. The small sample size of type III and IV stent misdeployments prohibited comparison with other types.

However, the cohort size was relatively large, compared with previous studies, and included a range of centers and countries with different strategies for managing stent misdeployments. Given the steep learning curve for EUS-GE, the study findings may help endoscopists better understand the implications and potential consequences of stent misdeployment by classifying the misdeployments into types. “We believe that such a classification or categorization of the different types is important because patient outcomes vary depending on the specific [stent misdeployment] subtype and site of injury. Such a classification will also be very helpful for future research by standardizing the terminology,” the researchers said.

“Although [stent misdeployment] is not infrequent during EUS-GE, with a rate of approximately 10%, the majority of cases are mild in severity and can be managed or repaired endoscopically without ill consequences,” they concluded. “Surgical intervention is required in less than 11% of the cases.”
 

Data support safe stent use in GI disease

“The lines continue to be blurred between surgical and endoscopic management of gastrointestinal disease, especially with a rise in therapeutic EUS,” Gyanprakash A. Ketwaroo, MD, of Baylor College of Medicine, Houston, said in an interview.

“Stent misdeployment has been commonly reported during EUS-GE and may limit uptake of this more technically challenging procedure,” Dr. Ketwaroo said. “A comprehensive assessment of stent misdeployment, with suggestions for management and a classification system that predicts outcomes, can help practitioners to more confidently perform this procedure.”

Risks associated with misdeployed stents include “inability to perform the endoscopic management of gastric outlet obstruction, as well as adverse events such as peritonitis,” said Dr. Ketwaroo. He noted that, in most cases, the defect was closed and same-session salvage was performed, primarily by repeat EUS-GE.

Dr. Ketwaroo highlighted one challenge to endoscopic management of stent misdeployment. “If the proximal flange is deployed/slips into peritoneum (type III by currently proposed classification system), it can be more difficult to retrieve the stent,” but “this complication was treated with surgery, and it was very rare – only one case of this in the study,” he explained. “This is a large retrospective multicenter study, which adds validity to the generalizability of the study.” However, prospective studies will be needed as EUS-GE is more widely adopted, he added.

The study received no outside funding. Lead author Dr. Ghandour had no financial conflicts to disclose. Other authors disclosed industry relationships, such as consulting for Boston Scientific, Apollo, Olympus America, Medtronic, and GI Supply. Dr. Ketwaroo had no financial conflicts to disclose, but serves as a member of the GI & Hepatology News editorial advisory board.

Most instances of stent misdeployment in cases of endoscopic ultrasound–guided gastroenterostomy (EUS-GE) can be managed endoscopically, based on data from 16 tertiary care centers in the United States and Europe.

EUS-GE provides a viable alternative to traditional surgical gastroenterostomy and stent placement for patients with gastric outlet obstruction (GOO), but the potential for stent misdeployment has limited adoption of the procedure because it remains the most common cause of technical failures and adverse events, Bachir Ghandour, MD, of Johns Hopkins University, Baltimore, and colleagues wrote.

However, data on outcomes and management of stent misdeployment during EUS-GE are limited, and the researchers hypothesized that most stent misdeployments could be managed endoscopically.

In a retrospective study published in Gastrointestinal Endoscopy, the researchers reviewed data from 467 EUS-GE procedures performed for gastric outlet obstruction between March 2015 and December 2020 at eight centers in the United States and eight in Europe. The primary outcome was the rate and severity of stent misdeployment.

Stent misdeployment occurred in 46 patients (9.9%). Of these, 73.2% occurred during the operators’ first 13 cases.

The researchers created a classification system of stent misdeployment according to type, depending on which flange was misdeployed.

Type I was the most common, and occurred in 29 patients; this type was defined as “the deployment of the distal flange in the peritoneum and proximal flange in the stomach without evidence of a resulting enterotomy”; type II (14 patients) was defined as “the deployment of the distal flange in the peritoneum and proximal flange in the stomach despite an enterotomy (i.e., visual confirmation of stent having penetrated targeted small bowel, under EUS or fluoroscopy, but migrated out on deployment)”; type III (1 patient) was defined as “the deployment of the distal flange in the small bowel and proximal flange in the peritoneum”; and type IV (2 patients) was defined as “the deployment of the distal flange in the colon and proximal flange in the stomach resulting in a gastrocolic anastomosis,” the researchers wrote.

The researchers also classified the stent misdeployment in terms of severity as mild (28 patients), moderate (11 patients), severe (6 cases) or fatal (1 case) based on the American Society for Gastrointestinal Endoscopy lexicon.

Overall, type I was significantly more likely to be mild in severity, compared with type II (75.9% vs. 42.9%; P = .04), although the rate of surgical repair was similar between these two types (10.3% vs. 7.1%). Rates of ICU admission were approximately 7% in patients with type I and type II stent misdeployments, and the median postprocedural stay was 4 days for these two groups.

Same-session salvage management of GOO was achieved by EUS/endoscopic-GE in 24 patients, duodenal stent placement in 6 patients, duodenal dilation in 1 patient, and gastroenterostomy with natural orifice transluminal endoscopic surgery in 3 patients. Of the remaining 12 patients, GOO was managed with subsequent EUS-GE in 6 patients and surgical GI in 6 patients.

The study findings were limited by several factors including the retrospective design and inclusion of a time period that encompassed changes and improvements in the EUS-GE, the researchers noted. The small sample size of type III and IV stent misdeployments prohibited comparison with other types.

However, the cohort size was relatively large, compared with previous studies, and included a range of centers and countries with different strategies for managing stent misdeployments. Given the steep learning curve for EUS-GE, the study findings may help endoscopists better understand the implications and potential consequences of stent misdeployment by classifying the misdeployments into types. “We believe that such a classification or categorization of the different types is important because patient outcomes vary depending on the specific [stent misdeployment] subtype and site of injury. Such a classification will also be very helpful for future research by standardizing the terminology,” the researchers said.

“Although [stent misdeployment] is not infrequent during EUS-GE, with a rate of approximately 10%, the majority of cases are mild in severity and can be managed or repaired endoscopically without ill consequences,” they concluded. “Surgical intervention is required in less than 11% of the cases.”
 

Data support safe stent use in GI disease

“The lines continue to be blurred between surgical and endoscopic management of gastrointestinal disease, especially with a rise in therapeutic EUS,” Gyanprakash A. Ketwaroo, MD, of Baylor College of Medicine, Houston, said in an interview.

“Stent misdeployment has been commonly reported during EUS-GE and may limit uptake of this more technically challenging procedure,” Dr. Ketwaroo said. “A comprehensive assessment of stent misdeployment, with suggestions for management and a classification system that predicts outcomes, can help practitioners to more confidently perform this procedure.”

Risks associated with misdeployed stents include “inability to perform the endoscopic management of gastric outlet obstruction, as well as adverse events such as peritonitis,” said Dr. Ketwaroo. He noted that, in most cases, the defect was closed and same-session salvage was performed, primarily by repeat EUS-GE.

Dr. Ketwaroo highlighted one challenge to endoscopic management of stent misdeployment. “If the proximal flange is deployed/slips into peritoneum (type III by currently proposed classification system), it can be more difficult to retrieve the stent,” but “this complication was treated with surgery, and it was very rare – only one case of this in the study,” he explained. “This is a large retrospective multicenter study, which adds validity to the generalizability of the study.” However, prospective studies will be needed as EUS-GE is more widely adopted, he added.

The study received no outside funding. Lead author Dr. Ghandour had no financial conflicts to disclose. Other authors disclosed industry relationships, such as consulting for Boston Scientific, Apollo, Olympus America, Medtronic, and GI Supply. Dr. Ketwaroo had no financial conflicts to disclose, but serves as a member of the GI & Hepatology News editorial advisory board.

Most instances of stent misdeployment in cases of endoscopic ultrasound–guided gastroenterostomy (EUS-GE) can be managed endoscopically, based on data from 16 tertiary care centers in the United States and Europe.

EUS-GE provides a viable alternative to traditional surgical gastroenterostomy and stent placement for patients with gastric outlet obstruction (GOO), but the potential for stent misdeployment has limited adoption of the procedure because it remains the most common cause of technical failures and adverse events, Bachir Ghandour, MD, of Johns Hopkins University, Baltimore, and colleagues wrote.

However, data on outcomes and management of stent misdeployment during EUS-GE are limited, and the researchers hypothesized that most stent misdeployments could be managed endoscopically.

In a retrospective study published in Gastrointestinal Endoscopy, the researchers reviewed data from 467 EUS-GE procedures performed for gastric outlet obstruction between March 2015 and December 2020 at eight centers in the United States and eight in Europe. The primary outcome was the rate and severity of stent misdeployment.

Stent misdeployment occurred in 46 patients (9.9%). Of these, 73.2% occurred during the operators’ first 13 cases.

The researchers created a classification system of stent misdeployment according to type, depending on which flange was misdeployed.

Type I was the most common, and occurred in 29 patients; this type was defined as “the deployment of the distal flange in the peritoneum and proximal flange in the stomach without evidence of a resulting enterotomy”; type II (14 patients) was defined as “the deployment of the distal flange in the peritoneum and proximal flange in the stomach despite an enterotomy (i.e., visual confirmation of stent having penetrated targeted small bowel, under EUS or fluoroscopy, but migrated out on deployment)”; type III (1 patient) was defined as “the deployment of the distal flange in the small bowel and proximal flange in the peritoneum”; and type IV (2 patients) was defined as “the deployment of the distal flange in the colon and proximal flange in the stomach resulting in a gastrocolic anastomosis,” the researchers wrote.

The researchers also classified the stent misdeployment in terms of severity as mild (28 patients), moderate (11 patients), severe (6 cases) or fatal (1 case) based on the American Society for Gastrointestinal Endoscopy lexicon.

Overall, type I was significantly more likely to be mild in severity, compared with type II (75.9% vs. 42.9%; P = .04), although the rate of surgical repair was similar between these two types (10.3% vs. 7.1%). Rates of ICU admission were approximately 7% in patients with type I and type II stent misdeployments, and the median postprocedural stay was 4 days for these two groups.

Same-session salvage management of GOO was achieved by EUS/endoscopic-GE in 24 patients, duodenal stent placement in 6 patients, duodenal dilation in 1 patient, and gastroenterostomy with natural orifice transluminal endoscopic surgery in 3 patients. Of the remaining 12 patients, GOO was managed with subsequent EUS-GE in 6 patients and surgical GI in 6 patients.

The study findings were limited by several factors including the retrospective design and inclusion of a time period that encompassed changes and improvements in the EUS-GE, the researchers noted. The small sample size of type III and IV stent misdeployments prohibited comparison with other types.

However, the cohort size was relatively large, compared with previous studies, and included a range of centers and countries with different strategies for managing stent misdeployments. Given the steep learning curve for EUS-GE, the study findings may help endoscopists better understand the implications and potential consequences of stent misdeployment by classifying the misdeployments into types. “We believe that such a classification or categorization of the different types is important because patient outcomes vary depending on the specific [stent misdeployment] subtype and site of injury. Such a classification will also be very helpful for future research by standardizing the terminology,” the researchers said.

“Although [stent misdeployment] is not infrequent during EUS-GE, with a rate of approximately 10%, the majority of cases are mild in severity and can be managed or repaired endoscopically without ill consequences,” they concluded. “Surgical intervention is required in less than 11% of the cases.”
 

Data support safe stent use in GI disease

“The lines continue to be blurred between surgical and endoscopic management of gastrointestinal disease, especially with a rise in therapeutic EUS,” Gyanprakash A. Ketwaroo, MD, of Baylor College of Medicine, Houston, said in an interview.

“Stent misdeployment has been commonly reported during EUS-GE and may limit uptake of this more technically challenging procedure,” Dr. Ketwaroo said. “A comprehensive assessment of stent misdeployment, with suggestions for management and a classification system that predicts outcomes, can help practitioners to more confidently perform this procedure.”

Risks associated with misdeployed stents include “inability to perform the endoscopic management of gastric outlet obstruction, as well as adverse events such as peritonitis,” said Dr. Ketwaroo. He noted that, in most cases, the defect was closed and same-session salvage was performed, primarily by repeat EUS-GE.

Dr. Ketwaroo highlighted one challenge to endoscopic management of stent misdeployment. “If the proximal flange is deployed/slips into peritoneum (type III by currently proposed classification system), it can be more difficult to retrieve the stent,” but “this complication was treated with surgery, and it was very rare – only one case of this in the study,” he explained. “This is a large retrospective multicenter study, which adds validity to the generalizability of the study.” However, prospective studies will be needed as EUS-GE is more widely adopted, he added.

The study received no outside funding. Lead author Dr. Ghandour had no financial conflicts to disclose. Other authors disclosed industry relationships, such as consulting for Boston Scientific, Apollo, Olympus America, Medtronic, and GI Supply. Dr. Ketwaroo had no financial conflicts to disclose, but serves as a member of the GI & Hepatology News editorial advisory board.

Bimekizumab has been approved by the European Commission for the treatment of moderate to severe plaque psoriasis in adults, according to a statement from the manufacturer.

Bimekizumab (Bimzelx), a humanized IgG1 monoclonal antibody, is the first approved treatment for moderate to severe plaque psoriasis that selectively inhibits interleukin (IL)–17A and IL-17F, the statement from UCB said.

In the United States, the Food and Drug Administration is expected to make a decision on approval of bimekizumab for treating psoriasis on Oct. 15.

Approval in the EU was based on data from three phase 3 trials including a total of 1,480 adult patients with moderate to severe psoriasis, which found that those treated with bimekizumab experienced significantly greater skin clearance, compared with placebo, ustekinumab, and adalimumab, with a favorable safety profile, according to the company.

In all three studies (BE VIVID, BE READY, and BE SURE), more than 80% of patients treated with bimekizumab showed improved skin clearance after 16 weeks, significantly more than those treated with ustekinumab, placebo, or adalimumab, based on an improvement of at least 90% in the Psoriasis Area & Severity Index (PASI 90) and an Investigator’s Global Assessment (IGA) response of clear or almost clear skin (IGA 0/1). In all three studies, these clinical responses persisted after 1 year.

The recommended dose of bimekizumab is 320 mg, given in two subcutaneous injections every 4 weeks to week 16, then every 8 weeks. However, for “some patients” weighing 120 kg or more who have not achieved complete skin clearance at 16 weeks, 320 mg every 4 weeks after that time may improve response to treatment, according to the company statement.

The most common treatment-related adverse events in the studies were upper respiratory tract infections (a majority of which were nasopharyngitis), reported by 14.5% of patients, followed by oral candidiasis, reported by 7.3%.

Results of BE READY and BE VIVID were published in The Lancet. Results of the BE SURE study were published in The New England Journal of Medicine.

Bimekizumab is contraindicated for individuals with clinically important active infections such as tuberculosis, and for individuals with any hypersensitivity to the active substance. More details on bimekizumab are available on the website of the European Medicines Agency.

Bimekizumab has been approved by the European Commission for the treatment of moderate to severe plaque psoriasis in adults, according to a statement from the manufacturer.

Bimekizumab (Bimzelx), a humanized IgG1 monoclonal antibody, is the first approved treatment for moderate to severe plaque psoriasis that selectively inhibits interleukin (IL)–17A and IL-17F, the statement from UCB said.

In the United States, the Food and Drug Administration is expected to make a decision on approval of bimekizumab for treating psoriasis on Oct. 15.

Approval in the EU was based on data from three phase 3 trials including a total of 1,480 adult patients with moderate to severe psoriasis, which found that those treated with bimekizumab experienced significantly greater skin clearance, compared with placebo, ustekinumab, and adalimumab, with a favorable safety profile, according to the company.

In all three studies (BE VIVID, BE READY, and BE SURE), more than 80% of patients treated with bimekizumab showed improved skin clearance after 16 weeks, significantly more than those treated with ustekinumab, placebo, or adalimumab, based on an improvement of at least 90% in the Psoriasis Area & Severity Index (PASI 90) and an Investigator’s Global Assessment (IGA) response of clear or almost clear skin (IGA 0/1). In all three studies, these clinical responses persisted after 1 year.

The recommended dose of bimekizumab is 320 mg, given in two subcutaneous injections every 4 weeks to week 16, then every 8 weeks. However, for “some patients” weighing 120 kg or more who have not achieved complete skin clearance at 16 weeks, 320 mg every 4 weeks after that time may improve response to treatment, according to the company statement.

The most common treatment-related adverse events in the studies were upper respiratory tract infections (a majority of which were nasopharyngitis), reported by 14.5% of patients, followed by oral candidiasis, reported by 7.3%.

Results of BE READY and BE VIVID were published in The Lancet. Results of the BE SURE study were published in The New England Journal of Medicine.

Bimekizumab is contraindicated for individuals with clinically important active infections such as tuberculosis, and for individuals with any hypersensitivity to the active substance. More details on bimekizumab are available on the website of the European Medicines Agency.

Bimekizumab has been approved by the European Commission for the treatment of moderate to severe plaque psoriasis in adults, according to a statement from the manufacturer.

Bimekizumab (Bimzelx), a humanized IgG1 monoclonal antibody, is the first approved treatment for moderate to severe plaque psoriasis that selectively inhibits interleukin (IL)–17A and IL-17F, the statement from UCB said.

In the United States, the Food and Drug Administration is expected to make a decision on approval of bimekizumab for treating psoriasis on Oct. 15.

Approval in the EU was based on data from three phase 3 trials including a total of 1,480 adult patients with moderate to severe psoriasis, which found that those treated with bimekizumab experienced significantly greater skin clearance, compared with placebo, ustekinumab, and adalimumab, with a favorable safety profile, according to the company.

In all three studies (BE VIVID, BE READY, and BE SURE), more than 80% of patients treated with bimekizumab showed improved skin clearance after 16 weeks, significantly more than those treated with ustekinumab, placebo, or adalimumab, based on an improvement of at least 90% in the Psoriasis Area & Severity Index (PASI 90) and an Investigator’s Global Assessment (IGA) response of clear or almost clear skin (IGA 0/1). In all three studies, these clinical responses persisted after 1 year.

The recommended dose of bimekizumab is 320 mg, given in two subcutaneous injections every 4 weeks to week 16, then every 8 weeks. However, for “some patients” weighing 120 kg or more who have not achieved complete skin clearance at 16 weeks, 320 mg every 4 weeks after that time may improve response to treatment, according to the company statement.

The most common treatment-related adverse events in the studies were upper respiratory tract infections (a majority of which were nasopharyngitis), reported by 14.5% of patients, followed by oral candidiasis, reported by 7.3%.

Results of BE READY and BE VIVID were published in The Lancet. Results of the BE SURE study were published in The New England Journal of Medicine.

Bimekizumab is contraindicated for individuals with clinically important active infections such as tuberculosis, and for individuals with any hypersensitivity to the active substance. More details on bimekizumab are available on the website of the European Medicines Agency.

Parkinson’s disease patients who develop anxiety early in their disease are at risk for reduced physical activity, which promotes further anxiety and cognitive decline, data from nearly 500 individuals show.

Anxiety occurs in 20%-60% of Parkinson’s disease (PD) patients but often goes undiagnosed, wrote Jacob D. Jones, PhD, of California State University, San Bernardino, and colleagues.

“Anxiety can attenuate motivation to engage in physical activity leading to more anxiety and other negative cognitive outcomes,” although physical activity has been shown to improve cognitive function in PD patients, they said. However, physical activity as a mediator between anxiety and cognitive function in PD has not been well studied, they noted.

In a study published in Mental Health and Physical Activity the researchers identified 487 adults with newly diagnosed PD within the past 2 years who were enrolled in the Parkinson’s Progression Markers Initiative. Participants were followed for up to 5 years and completed neuropsychological tests, tests of motor severity, and self-reports on anxiety and physical activity. Anxiety was assessed using the State-Trait Anxiety Inventory-Trait (STAI-T) subscale. Physical activity was assessed using the Physical Activity Scale for the Elderly (PASE). Motor severity was assessed using the Unified Parkinson’s Disease Rating Scale-Part III (UPDRS). The average age of the participants was 61 years, 65% were men, and 96% were White.

Using a direct-effect model, the researchers found that individuals whose anxiety increased during the study period also showed signs of cognitive decline. A significant between-person effect showed that individuals who were generally more anxious also scored lower on cognitive tests over the 5-year study period.

In a mediation model computed with structural equation modeling, physical activity mediated the link between anxiety and cognition, most notably household activity.

“There was a significant within-person association between anxiety and household activities, meaning that individuals who became more anxious over the 5-year study also became less active in the home,” reported Dr. Jones and colleagues.

However, no significant indirect effect was noted regarding the between-person findings of the impact of physical activity on anxiety and cognitive decline. Although more severe anxiety was associated with less activity, cognitive performance was not associated with either type of physical activity.

The presence of a within-person effect “suggests that reductions in physical activity, specifically within the first 5 years of disease onset, may be detrimental to mental health,” the researchers emphasized. Given that the study population was newly diagnosed with PD “it is likely the within-person terms are more sensitive to changes in anxiety, physical activity, and cognition that are more directly the result of the PD process, as opposed to lifestyle/preexisting traits,” they said.

The study findings were limited by several factors, including the use of self-reports to measure physical activity, and the lack of granular information about the details of physical activity, the researchers noted. Another limitation was the inclusion of only newly diagnosed PD patients, which might limit generalizability.

“Future research is warranted to understand if other modes, intensities, or complexities of physical activity impact individuals with PD in a different manner in relation to cognition,” they said.

Dr. Jones and colleagues had no disclosures. The PPMI is supported by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, including numerous pharmaceutical companies.

Parkinson’s disease patients who develop anxiety early in their disease are at risk for reduced physical activity, which promotes further anxiety and cognitive decline, data from nearly 500 individuals show.

Anxiety occurs in 20%-60% of Parkinson’s disease (PD) patients but often goes undiagnosed, wrote Jacob D. Jones, PhD, of California State University, San Bernardino, and colleagues.

“Anxiety can attenuate motivation to engage in physical activity leading to more anxiety and other negative cognitive outcomes,” although physical activity has been shown to improve cognitive function in PD patients, they said. However, physical activity as a mediator between anxiety and cognitive function in PD has not been well studied, they noted.

In a study published in Mental Health and Physical Activity the researchers identified 487 adults with newly diagnosed PD within the past 2 years who were enrolled in the Parkinson’s Progression Markers Initiative. Participants were followed for up to 5 years and completed neuropsychological tests, tests of motor severity, and self-reports on anxiety and physical activity. Anxiety was assessed using the State-Trait Anxiety Inventory-Trait (STAI-T) subscale. Physical activity was assessed using the Physical Activity Scale for the Elderly (PASE). Motor severity was assessed using the Unified Parkinson’s Disease Rating Scale-Part III (UPDRS). The average age of the participants was 61 years, 65% were men, and 96% were White.

Using a direct-effect model, the researchers found that individuals whose anxiety increased during the study period also showed signs of cognitive decline. A significant between-person effect showed that individuals who were generally more anxious also scored lower on cognitive tests over the 5-year study period.

In a mediation model computed with structural equation modeling, physical activity mediated the link between anxiety and cognition, most notably household activity.

“There was a significant within-person association between anxiety and household activities, meaning that individuals who became more anxious over the 5-year study also became less active in the home,” reported Dr. Jones and colleagues.

However, no significant indirect effect was noted regarding the between-person findings of the impact of physical activity on anxiety and cognitive decline. Although more severe anxiety was associated with less activity, cognitive performance was not associated with either type of physical activity.

The presence of a within-person effect “suggests that reductions in physical activity, specifically within the first 5 years of disease onset, may be detrimental to mental health,” the researchers emphasized. Given that the study population was newly diagnosed with PD “it is likely the within-person terms are more sensitive to changes in anxiety, physical activity, and cognition that are more directly the result of the PD process, as opposed to lifestyle/preexisting traits,” they said.

The study findings were limited by several factors, including the use of self-reports to measure physical activity, and the lack of granular information about the details of physical activity, the researchers noted. Another limitation was the inclusion of only newly diagnosed PD patients, which might limit generalizability.

“Future research is warranted to understand if other modes, intensities, or complexities of physical activity impact individuals with PD in a different manner in relation to cognition,” they said.

Dr. Jones and colleagues had no disclosures. The PPMI is supported by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, including numerous pharmaceutical companies.

Parkinson’s disease patients who develop anxiety early in their disease are at risk for reduced physical activity, which promotes further anxiety and cognitive decline, data from nearly 500 individuals show.

Anxiety occurs in 20%-60% of Parkinson’s disease (PD) patients but often goes undiagnosed, wrote Jacob D. Jones, PhD, of California State University, San Bernardino, and colleagues.

“Anxiety can attenuate motivation to engage in physical activity leading to more anxiety and other negative cognitive outcomes,” although physical activity has been shown to improve cognitive function in PD patients, they said. However, physical activity as a mediator between anxiety and cognitive function in PD has not been well studied, they noted.

In a study published in Mental Health and Physical Activity the researchers identified 487 adults with newly diagnosed PD within the past 2 years who were enrolled in the Parkinson’s Progression Markers Initiative. Participants were followed for up to 5 years and completed neuropsychological tests, tests of motor severity, and self-reports on anxiety and physical activity. Anxiety was assessed using the State-Trait Anxiety Inventory-Trait (STAI-T) subscale. Physical activity was assessed using the Physical Activity Scale for the Elderly (PASE). Motor severity was assessed using the Unified Parkinson’s Disease Rating Scale-Part III (UPDRS). The average age of the participants was 61 years, 65% were men, and 96% were White.

Using a direct-effect model, the researchers found that individuals whose anxiety increased during the study period also showed signs of cognitive decline. A significant between-person effect showed that individuals who were generally more anxious also scored lower on cognitive tests over the 5-year study period.

In a mediation model computed with structural equation modeling, physical activity mediated the link between anxiety and cognition, most notably household activity.

“There was a significant within-person association between anxiety and household activities, meaning that individuals who became more anxious over the 5-year study also became less active in the home,” reported Dr. Jones and colleagues.

However, no significant indirect effect was noted regarding the between-person findings of the impact of physical activity on anxiety and cognitive decline. Although more severe anxiety was associated with less activity, cognitive performance was not associated with either type of physical activity.

The presence of a within-person effect “suggests that reductions in physical activity, specifically within the first 5 years of disease onset, may be detrimental to mental health,” the researchers emphasized. Given that the study population was newly diagnosed with PD “it is likely the within-person terms are more sensitive to changes in anxiety, physical activity, and cognition that are more directly the result of the PD process, as opposed to lifestyle/preexisting traits,” they said.

The study findings were limited by several factors, including the use of self-reports to measure physical activity, and the lack of granular information about the details of physical activity, the researchers noted. Another limitation was the inclusion of only newly diagnosed PD patients, which might limit generalizability.

“Future research is warranted to understand if other modes, intensities, or complexities of physical activity impact individuals with PD in a different manner in relation to cognition,” they said.

Dr. Jones and colleagues had no disclosures. The PPMI is supported by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, including numerous pharmaceutical companies.

Adults aged 65 years and older who develop psychotic manifestations are significantly more likely than those without such manifestations to develop prodromal Parkinson’s disease, data from 925 individuals suggest.

“The presence of perceptual abnormalities and/or delusional ideation among community-dwelling elderly individuals is more widespread than considered in the past,” wrote Ioanna Pachi, MD, of National and Kapodistrian University of Athens Medical School and colleagues. However, those psychoses and their potential impact on prodromal Parkinson’s disease (PD) have not been well studied in community-dwelling populations, they noted in the study, published in Parkinsonism and Related Disorders.

In the study, Dr. Pachi and colleagues reviewed data from 914 participants in the Hellenic Longitudinal Investigation of Aging and Diet study (HELIAD), a cross-sectional, population-based cohort study of older adults in Greece. The average age of the participants was 76 years, and 41% were men. Participants had no delusional features at baseline; delusional features were assessed using the Neuropsychiatric Inventory scale and the Columbia University Scale for Psychopathology in Alzheimer’s disease. The researchers calculated the probability of prodromal PD (pPD) for each participant based on the 2019 International Parkinson and Movement Disorders Society research criteria for prodromal PD.

Over a 3-year follow-up period, 20 participants developed psychotic manifestations and were 1.3 times more likely to have pPD, compared with those without psychoses (P = .006). Those with new-onset psychotic features were categorized together as the NPSY group, regardless of symptom severity or frequency; those with no symptoms at either baseline or during follow-up were categorized as unaffected (UPSY). Most of the NPSY participants showed isolated delusional features, although some expressed hallucinations. Most symptoms were mild.

New-onset psychosis was associated with a fivefold increased risk of both subthreshold parkinsonism and depression (adjusted odds ratios, 4.5 and 5.0, respectively) and with a threefold increased risk of constipation (aOR 2.6). Other factors, including nonsmoking, global cognitive deficit, and anxiety were not significantly associated with new-onset psychotic symptoms after adjusting for confounding factors.

Although the mechanism behind the association remains unclear, “the parallel evolution of psychotic features and prodromal PD could be related to the spreading pattern of neuronal damage that occurs in PD,” the researchers wrote.

The study findings were limited by several factors, including the administration of neuropsychiatric questionnaires by nonpsychiatrists, and lack of detailed psychiatric history, including complete information on medication use, the researchers noted. The small size of the NPSY group also prevented evaluation of the potential associations between pPD and different modalities of hallucinations, they said.

However, the results were strengthened by the overall large and population-based sample size, and the comprehensive evaluation of psychotic features, they wrote. More follow-up evaluations in the HELIAD cohort are planned to further explore the underlying mechanism of the association between late-life psychosis and pPD.

“Provided that these results are confirmed in other community cohorts of elderly subjects, psychotic features may be added to the list of manifestations of pPD,” they concluded.

The study was supported in part by grants from the Alzheimer’s Association, ARISTEIA, and the ESPA-EU program Excellence Grant. It was cofunded by the European Social Fund and Greek National resources, the Ministry for Health and Social Solidarity, Greece, and the Greek State Scholarships Foundation. Dr. Pachi had no disclosures.

Adults aged 65 years and older who develop psychotic manifestations are significantly more likely than those without such manifestations to develop prodromal Parkinson’s disease, data from 925 individuals suggest.

“The presence of perceptual abnormalities and/or delusional ideation among community-dwelling elderly individuals is more widespread than considered in the past,” wrote Ioanna Pachi, MD, of National and Kapodistrian University of Athens Medical School and colleagues. However, those psychoses and their potential impact on prodromal Parkinson’s disease (PD) have not been well studied in community-dwelling populations, they noted in the study, published in Parkinsonism and Related Disorders.

In the study, Dr. Pachi and colleagues reviewed data from 914 participants in the Hellenic Longitudinal Investigation of Aging and Diet study (HELIAD), a cross-sectional, population-based cohort study of older adults in Greece. The average age of the participants was 76 years, and 41% were men. Participants had no delusional features at baseline; delusional features were assessed using the Neuropsychiatric Inventory scale and the Columbia University Scale for Psychopathology in Alzheimer’s disease. The researchers calculated the probability of prodromal PD (pPD) for each participant based on the 2019 International Parkinson and Movement Disorders Society research criteria for prodromal PD.

Over a 3-year follow-up period, 20 participants developed psychotic manifestations and were 1.3 times more likely to have pPD, compared with those without psychoses (P = .006). Those with new-onset psychotic features were categorized together as the NPSY group, regardless of symptom severity or frequency; those with no symptoms at either baseline or during follow-up were categorized as unaffected (UPSY). Most of the NPSY participants showed isolated delusional features, although some expressed hallucinations. Most symptoms were mild.

New-onset psychosis was associated with a fivefold increased risk of both subthreshold parkinsonism and depression (adjusted odds ratios, 4.5 and 5.0, respectively) and with a threefold increased risk of constipation (aOR 2.6). Other factors, including nonsmoking, global cognitive deficit, and anxiety were not significantly associated with new-onset psychotic symptoms after adjusting for confounding factors.

Although the mechanism behind the association remains unclear, “the parallel evolution of psychotic features and prodromal PD could be related to the spreading pattern of neuronal damage that occurs in PD,” the researchers wrote.

The study findings were limited by several factors, including the administration of neuropsychiatric questionnaires by nonpsychiatrists, and lack of detailed psychiatric history, including complete information on medication use, the researchers noted. The small size of the NPSY group also prevented evaluation of the potential associations between pPD and different modalities of hallucinations, they said.

However, the results were strengthened by the overall large and population-based sample size, and the comprehensive evaluation of psychotic features, they wrote. More follow-up evaluations in the HELIAD cohort are planned to further explore the underlying mechanism of the association between late-life psychosis and pPD.

“Provided that these results are confirmed in other community cohorts of elderly subjects, psychotic features may be added to the list of manifestations of pPD,” they concluded.

The study was supported in part by grants from the Alzheimer’s Association, ARISTEIA, and the ESPA-EU program Excellence Grant. It was cofunded by the European Social Fund and Greek National resources, the Ministry for Health and Social Solidarity, Greece, and the Greek State Scholarships Foundation. Dr. Pachi had no disclosures.

Adults aged 65 years and older who develop psychotic manifestations are significantly more likely than those without such manifestations to develop prodromal Parkinson’s disease, data from 925 individuals suggest.

“The presence of perceptual abnormalities and/or delusional ideation among community-dwelling elderly individuals is more widespread than considered in the past,” wrote Ioanna Pachi, MD, of National and Kapodistrian University of Athens Medical School and colleagues. However, those psychoses and their potential impact on prodromal Parkinson’s disease (PD) have not been well studied in community-dwelling populations, they noted in the study, published in Parkinsonism and Related Disorders.

In the study, Dr. Pachi and colleagues reviewed data from 914 participants in the Hellenic Longitudinal Investigation of Aging and Diet study (HELIAD), a cross-sectional, population-based cohort study of older adults in Greece. The average age of the participants was 76 years, and 41% were men. Participants had no delusional features at baseline; delusional features were assessed using the Neuropsychiatric Inventory scale and the Columbia University Scale for Psychopathology in Alzheimer’s disease. The researchers calculated the probability of prodromal PD (pPD) for each participant based on the 2019 International Parkinson and Movement Disorders Society research criteria for prodromal PD.

Over a 3-year follow-up period, 20 participants developed psychotic manifestations and were 1.3 times more likely to have pPD, compared with those without psychoses (P = .006). Those with new-onset psychotic features were categorized together as the NPSY group, regardless of symptom severity or frequency; those with no symptoms at either baseline or during follow-up were categorized as unaffected (UPSY). Most of the NPSY participants showed isolated delusional features, although some expressed hallucinations. Most symptoms were mild.

New-onset psychosis was associated with a fivefold increased risk of both subthreshold parkinsonism and depression (adjusted odds ratios, 4.5 and 5.0, respectively) and with a threefold increased risk of constipation (aOR 2.6). Other factors, including nonsmoking, global cognitive deficit, and anxiety were not significantly associated with new-onset psychotic symptoms after adjusting for confounding factors.

Although the mechanism behind the association remains unclear, “the parallel evolution of psychotic features and prodromal PD could be related to the spreading pattern of neuronal damage that occurs in PD,” the researchers wrote.

The study findings were limited by several factors, including the administration of neuropsychiatric questionnaires by nonpsychiatrists, and lack of detailed psychiatric history, including complete information on medication use, the researchers noted. The small size of the NPSY group also prevented evaluation of the potential associations between pPD and different modalities of hallucinations, they said.

However, the results were strengthened by the overall large and population-based sample size, and the comprehensive evaluation of psychotic features, they wrote. More follow-up evaluations in the HELIAD cohort are planned to further explore the underlying mechanism of the association between late-life psychosis and pPD.

“Provided that these results are confirmed in other community cohorts of elderly subjects, psychotic features may be added to the list of manifestations of pPD,” they concluded.

The study was supported in part by grants from the Alzheimer’s Association, ARISTEIA, and the ESPA-EU program Excellence Grant. It was cofunded by the European Social Fund and Greek National resources, the Ministry for Health and Social Solidarity, Greece, and the Greek State Scholarships Foundation. Dr. Pachi had no disclosures.

The use fluoroquinolones or macrolides reduced immunogenicity risk in inflammatory bowel disease (IBD) patients on anti–tumor necrosis factor (anti-TNF) therapy, according to data from nearly 2,000 individuals.

luchschen/Thinkstock

Anti-TNF therapy with monoclonal antibodies is an established treatment for Crohn’s disease and ulcerative colitis, but approximately 40% of patients fail to respond initially and even more fail to achieve complete remission, wrote Yuri Gorelik, MD, of Rambam Health Care Campus, Haifa, Israel, and colleagues.

“Immunogenicity, which refers to the development of antidrug antibodies [ADA] is considered as the main factor driving secondary loss of response and is likely involved in primary nonresponse as well,” but data on how to predict the risk for ADA formation are limited, they said.

In a study published in Gut, the researchers identified data from 1,946 IBD patients using the epi-IIRN (epidemiology group of the Israeli IBD research nucleus), a nationwide registry of all IBD patients in Israel.

A total of 363 patients had positive ADA after a median follow-up period of 651 days after starting therapy. Overall, the risk of ADA development was significantly higher in patients on cephalosporins (adjusted hazard ratio, 1.97; 95% confidence interval, 1.58-2.44) or penicillin with beta-lactamase inhibitors (BLIs) (aHR, 1.38; 95% CI, 1.13-1.74) during anti-TNF therapy, and it was higher still for patients using both. By contrast, the risk was lower in patients on macrolides (aHR, 0.36; 95% CI, 0.16-0.82) or fluoroquinolones (aHR, 0.20; 95% CI; 95% CI, 0.12-0.35). All P values were less than .05 when compared with nontreated groups.

In the same study, the researchers reported data on mice treated with antibiotics and challenged with infliximab to evaluate the causative effect of antibiotics and the associated disruption to the gut microbiome on the formation of ADA. After 14 days, the researchers found significantly increased ADA production in mice treated with cephalosporins, compared with those treated with macrolides, but germ-free mice produced no ADA, which supports the role of microbial composition on ADA production.

The investigators cited previous research into the microbiome as a biomarker for prediction response to anti-TNF therapy; past results have also suggested that the effect of cephalosporins and penicillin-BLIs could be explained by the particular dysbiosis induced by those agents.

The study findings were limited by several factors including the retrospective design and potential for selection bias, as well as the inability to adjust antibiotic exposure according to type and severity of infection, they noted. However, “this is the first large scale study that extensively evaluated the effect of different antibiotic classes on immunogenicity of anti-TNF therapy,” and the results suggest that ADA development during anti-TNF therapy may to reduced by the use of fluoroquinolones and macrolides.

“Specific microbial manipulation may serve as a tool to modify immunogenicity which is preferably turned on for protective immunizations and off for biological therapy,” they noted. “Further studies involving detailed analysis of the antibiotic effects on the human microbiome and immune milieu are needed, as well as comparative experiments with other medications used to reduce immunogenicity.”
 

Unexpected findings may drive future drug choices

“Development of antidrug antibodies in patients on biologics for inflammatory bowel disease is an important mechanism for loss of response to a therapeutic agent,” Kim L. Isaacs, MD, AGAF, of the University of North Carolina at Chapel Hill, said in an interview. “To date the causes of development of ADAs is relatively understudied. Our approach to prevent ADA includes increasing immunosuppression in patients most commonly with combination therapy with thiopurines. If factors that provoke or prevent antibody formation are elucidated, therapy can be tailored to prevent ADAs and maximize the duration of response of many of our biologic therapies.”

A prior study performed by the ABIRISK European consortium demonstrated associations with antibiotics. “In the current study, there was a differential effect of cephalosporins/penicillins (increased immunogenicity) and macrolides (decreased immunogenicity),” she said. “These studies suggest that the microbiome may be important in ADA formation to biologics – this is a concept that is novel and unexpected.

“The rationale for the choice of antibiotics in the population studied is not known, and it is possible that different infections may have led to different antibiotic choices, which in turn may have affected immunogenicity,” said Dr. Isaacs. However, clinicians might be able to tailor antibiotic choice in the future if the microbiome is playing a major role in risk for development of ADA.

“Further research is needed to further correlate microbiome changes with immunogenicity, to look at other classes of antibiotics and their role in immunogenicity, and to clarify the infections or reasons that these patients are receiving antibiotics,” Dr. Isaacs concluded.
 

Understanding the microbiome

Recent observations have shown associations between clinical response to anti-TNF and gut microbiota composition, noted Jatin Roper, MD, of Duke University, Durham, N.C. “More broadly, a growing body of evidence suggests that the gut microbiota modulates the metabolism of many therapeutic agents, as well as immune responses to infections.”

That said, Dr. Roper was surprised that “clinical use of different antibiotics, often short term, had such distinct effects on ADA levels.” Furthermore, “these findings suggest that distinct microbiota or microbial metabolic products impact antibody development to common immunomodulatory therapies in opposite ways,” which is itself a surprising finding.

Such antibodies to anti-TNF therapy are common in IBD, he said, but one implication of the study is how antibiotics could be carefully used “to reduce risk of ADAs and enhance efficacy of anti-TNF therapy.”

However, because any antibiotic therapy will modify the gut microbiome and lead to unwanted effects, “further research is needed on how these agents impact the gut microbiome, with the ultimate goal of identifying specific microbiota or microbial metabolic products that can reproduce the intriguing findings of this paper.”

The study was supported in part by the Leona M. and Harry B. Helmsley Charitable Trust and the Israeli Ministry of Science and Technology. Dr. Gorelik had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple pharmaceutical companies including AbbVie, CytoReason, Takeda, and Pfizer. Dr. Isaacs had no financial conflicts to disclose, but serves on the GI&Hepatology News board of editors. Dr. Roper had no relevant disclosures.

Help your patients better understand their IBD treatment options by sharing AGA’s patient education, “Living with IBD,” in the AGA GI Patient Center at www.gastro.org/IBD. 

The use fluoroquinolones or macrolides reduced immunogenicity risk in inflammatory bowel disease (IBD) patients on anti–tumor necrosis factor (anti-TNF) therapy, according to data from nearly 2,000 individuals.

luchschen/Thinkstock

Anti-TNF therapy with monoclonal antibodies is an established treatment for Crohn’s disease and ulcerative colitis, but approximately 40% of patients fail to respond initially and even more fail to achieve complete remission, wrote Yuri Gorelik, MD, of Rambam Health Care Campus, Haifa, Israel, and colleagues.

“Immunogenicity, which refers to the development of antidrug antibodies [ADA] is considered as the main factor driving secondary loss of response and is likely involved in primary nonresponse as well,” but data on how to predict the risk for ADA formation are limited, they said.

In a study published in Gut, the researchers identified data from 1,946 IBD patients using the epi-IIRN (epidemiology group of the Israeli IBD research nucleus), a nationwide registry of all IBD patients in Israel.

A total of 363 patients had positive ADA after a median follow-up period of 651 days after starting therapy. Overall, the risk of ADA development was significantly higher in patients on cephalosporins (adjusted hazard ratio, 1.97; 95% confidence interval, 1.58-2.44) or penicillin with beta-lactamase inhibitors (BLIs) (aHR, 1.38; 95% CI, 1.13-1.74) during anti-TNF therapy, and it was higher still for patients using both. By contrast, the risk was lower in patients on macrolides (aHR, 0.36; 95% CI, 0.16-0.82) or fluoroquinolones (aHR, 0.20; 95% CI; 95% CI, 0.12-0.35). All P values were less than .05 when compared with nontreated groups.

In the same study, the researchers reported data on mice treated with antibiotics and challenged with infliximab to evaluate the causative effect of antibiotics and the associated disruption to the gut microbiome on the formation of ADA. After 14 days, the researchers found significantly increased ADA production in mice treated with cephalosporins, compared with those treated with macrolides, but germ-free mice produced no ADA, which supports the role of microbial composition on ADA production.

The investigators cited previous research into the microbiome as a biomarker for prediction response to anti-TNF therapy; past results have also suggested that the effect of cephalosporins and penicillin-BLIs could be explained by the particular dysbiosis induced by those agents.

The study findings were limited by several factors including the retrospective design and potential for selection bias, as well as the inability to adjust antibiotic exposure according to type and severity of infection, they noted. However, “this is the first large scale study that extensively evaluated the effect of different antibiotic classes on immunogenicity of anti-TNF therapy,” and the results suggest that ADA development during anti-TNF therapy may to reduced by the use of fluoroquinolones and macrolides.

“Specific microbial manipulation may serve as a tool to modify immunogenicity which is preferably turned on for protective immunizations and off for biological therapy,” they noted. “Further studies involving detailed analysis of the antibiotic effects on the human microbiome and immune milieu are needed, as well as comparative experiments with other medications used to reduce immunogenicity.”
 

Unexpected findings may drive future drug choices

“Development of antidrug antibodies in patients on biologics for inflammatory bowel disease is an important mechanism for loss of response to a therapeutic agent,” Kim L. Isaacs, MD, AGAF, of the University of North Carolina at Chapel Hill, said in an interview. “To date the causes of development of ADAs is relatively understudied. Our approach to prevent ADA includes increasing immunosuppression in patients most commonly with combination therapy with thiopurines. If factors that provoke or prevent antibody formation are elucidated, therapy can be tailored to prevent ADAs and maximize the duration of response of many of our biologic therapies.”

A prior study performed by the ABIRISK European consortium demonstrated associations with antibiotics. “In the current study, there was a differential effect of cephalosporins/penicillins (increased immunogenicity) and macrolides (decreased immunogenicity),” she said. “These studies suggest that the microbiome may be important in ADA formation to biologics – this is a concept that is novel and unexpected.

“The rationale for the choice of antibiotics in the population studied is not known, and it is possible that different infections may have led to different antibiotic choices, which in turn may have affected immunogenicity,” said Dr. Isaacs. However, clinicians might be able to tailor antibiotic choice in the future if the microbiome is playing a major role in risk for development of ADA.

“Further research is needed to further correlate microbiome changes with immunogenicity, to look at other classes of antibiotics and their role in immunogenicity, and to clarify the infections or reasons that these patients are receiving antibiotics,” Dr. Isaacs concluded.
 

Understanding the microbiome

Recent observations have shown associations between clinical response to anti-TNF and gut microbiota composition, noted Jatin Roper, MD, of Duke University, Durham, N.C. “More broadly, a growing body of evidence suggests that the gut microbiota modulates the metabolism of many therapeutic agents, as well as immune responses to infections.”

That said, Dr. Roper was surprised that “clinical use of different antibiotics, often short term, had such distinct effects on ADA levels.” Furthermore, “these findings suggest that distinct microbiota or microbial metabolic products impact antibody development to common immunomodulatory therapies in opposite ways,” which is itself a surprising finding.

Such antibodies to anti-TNF therapy are common in IBD, he said, but one implication of the study is how antibiotics could be carefully used “to reduce risk of ADAs and enhance efficacy of anti-TNF therapy.”

However, because any antibiotic therapy will modify the gut microbiome and lead to unwanted effects, “further research is needed on how these agents impact the gut microbiome, with the ultimate goal of identifying specific microbiota or microbial metabolic products that can reproduce the intriguing findings of this paper.”

The study was supported in part by the Leona M. and Harry B. Helmsley Charitable Trust and the Israeli Ministry of Science and Technology. Dr. Gorelik had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple pharmaceutical companies including AbbVie, CytoReason, Takeda, and Pfizer. Dr. Isaacs had no financial conflicts to disclose, but serves on the GI&Hepatology News board of editors. Dr. Roper had no relevant disclosures.

Help your patients better understand their IBD treatment options by sharing AGA’s patient education, “Living with IBD,” in the AGA GI Patient Center at www.gastro.org/IBD. 

The use fluoroquinolones or macrolides reduced immunogenicity risk in inflammatory bowel disease (IBD) patients on anti–tumor necrosis factor (anti-TNF) therapy, according to data from nearly 2,000 individuals.

luchschen/Thinkstock

Anti-TNF therapy with monoclonal antibodies is an established treatment for Crohn’s disease and ulcerative colitis, but approximately 40% of patients fail to respond initially and even more fail to achieve complete remission, wrote Yuri Gorelik, MD, of Rambam Health Care Campus, Haifa, Israel, and colleagues.

“Immunogenicity, which refers to the development of antidrug antibodies [ADA] is considered as the main factor driving secondary loss of response and is likely involved in primary nonresponse as well,” but data on how to predict the risk for ADA formation are limited, they said.

In a study published in Gut, the researchers identified data from 1,946 IBD patients using the epi-IIRN (epidemiology group of the Israeli IBD research nucleus), a nationwide registry of all IBD patients in Israel.

A total of 363 patients had positive ADA after a median follow-up period of 651 days after starting therapy. Overall, the risk of ADA development was significantly higher in patients on cephalosporins (adjusted hazard ratio, 1.97; 95% confidence interval, 1.58-2.44) or penicillin with beta-lactamase inhibitors (BLIs) (aHR, 1.38; 95% CI, 1.13-1.74) during anti-TNF therapy, and it was higher still for patients using both. By contrast, the risk was lower in patients on macrolides (aHR, 0.36; 95% CI, 0.16-0.82) or fluoroquinolones (aHR, 0.20; 95% CI; 95% CI, 0.12-0.35). All P values were less than .05 when compared with nontreated groups.

In the same study, the researchers reported data on mice treated with antibiotics and challenged with infliximab to evaluate the causative effect of antibiotics and the associated disruption to the gut microbiome on the formation of ADA. After 14 days, the researchers found significantly increased ADA production in mice treated with cephalosporins, compared with those treated with macrolides, but germ-free mice produced no ADA, which supports the role of microbial composition on ADA production.

The investigators cited previous research into the microbiome as a biomarker for prediction response to anti-TNF therapy; past results have also suggested that the effect of cephalosporins and penicillin-BLIs could be explained by the particular dysbiosis induced by those agents.

The study findings were limited by several factors including the retrospective design and potential for selection bias, as well as the inability to adjust antibiotic exposure according to type and severity of infection, they noted. However, “this is the first large scale study that extensively evaluated the effect of different antibiotic classes on immunogenicity of anti-TNF therapy,” and the results suggest that ADA development during anti-TNF therapy may to reduced by the use of fluoroquinolones and macrolides.

“Specific microbial manipulation may serve as a tool to modify immunogenicity which is preferably turned on for protective immunizations and off for biological therapy,” they noted. “Further studies involving detailed analysis of the antibiotic effects on the human microbiome and immune milieu are needed, as well as comparative experiments with other medications used to reduce immunogenicity.”
 

Unexpected findings may drive future drug choices

“Development of antidrug antibodies in patients on biologics for inflammatory bowel disease is an important mechanism for loss of response to a therapeutic agent,” Kim L. Isaacs, MD, AGAF, of the University of North Carolina at Chapel Hill, said in an interview. “To date the causes of development of ADAs is relatively understudied. Our approach to prevent ADA includes increasing immunosuppression in patients most commonly with combination therapy with thiopurines. If factors that provoke or prevent antibody formation are elucidated, therapy can be tailored to prevent ADAs and maximize the duration of response of many of our biologic therapies.”

A prior study performed by the ABIRISK European consortium demonstrated associations with antibiotics. “In the current study, there was a differential effect of cephalosporins/penicillins (increased immunogenicity) and macrolides (decreased immunogenicity),” she said. “These studies suggest that the microbiome may be important in ADA formation to biologics – this is a concept that is novel and unexpected.

“The rationale for the choice of antibiotics in the population studied is not known, and it is possible that different infections may have led to different antibiotic choices, which in turn may have affected immunogenicity,” said Dr. Isaacs. However, clinicians might be able to tailor antibiotic choice in the future if the microbiome is playing a major role in risk for development of ADA.

“Further research is needed to further correlate microbiome changes with immunogenicity, to look at other classes of antibiotics and their role in immunogenicity, and to clarify the infections or reasons that these patients are receiving antibiotics,” Dr. Isaacs concluded.
 

Understanding the microbiome

Recent observations have shown associations between clinical response to anti-TNF and gut microbiota composition, noted Jatin Roper, MD, of Duke University, Durham, N.C. “More broadly, a growing body of evidence suggests that the gut microbiota modulates the metabolism of many therapeutic agents, as well as immune responses to infections.”

That said, Dr. Roper was surprised that “clinical use of different antibiotics, often short term, had such distinct effects on ADA levels.” Furthermore, “these findings suggest that distinct microbiota or microbial metabolic products impact antibody development to common immunomodulatory therapies in opposite ways,” which is itself a surprising finding.

Such antibodies to anti-TNF therapy are common in IBD, he said, but one implication of the study is how antibiotics could be carefully used “to reduce risk of ADAs and enhance efficacy of anti-TNF therapy.”

However, because any antibiotic therapy will modify the gut microbiome and lead to unwanted effects, “further research is needed on how these agents impact the gut microbiome, with the ultimate goal of identifying specific microbiota or microbial metabolic products that can reproduce the intriguing findings of this paper.”

The study was supported in part by the Leona M. and Harry B. Helmsley Charitable Trust and the Israeli Ministry of Science and Technology. Dr. Gorelik had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple pharmaceutical companies including AbbVie, CytoReason, Takeda, and Pfizer. Dr. Isaacs had no financial conflicts to disclose, but serves on the GI&Hepatology News board of editors. Dr. Roper had no relevant disclosures.

Help your patients better understand their IBD treatment options by sharing AGA’s patient education, “Living with IBD,” in the AGA GI Patient Center at www.gastro.org/IBD. 

The use fluoroquinolones or macrolides reduced immunogenicity risk in inflammatory bowel disease (IBD) patients on anti–tumor necrosis factor (anti-TNF) therapy, according to data from nearly 2,000 individuals.

luchschen/Thinkstock

Anti-TNF therapy with monoclonal antibodies is an established treatment for Crohn’s disease and ulcerative colitis, but approximately 40% of patients fail to respond initially and even more fail to achieve complete remission, wrote Yuri Gorelik, MD, of Rambam Health Care Campus, Haifa, Israel, and colleagues.

“Immunogenicity, which refers to the development of antidrug antibodies [ADA] is considered as the main factor driving secondary loss of response and is likely involved in primary nonresponse as well,” but data on how to predict the risk for ADA formation are limited, they said.

In a study published in Gut, the researchers identified data from 1,946 IBD patients using the epi-IIRN (epidemiology group of the Israeli IBD research nucleus), a nationwide registry of all IBD patients in Israel.

A total of 363 patients had positive ADA after a median follow-up period of 651 days after starting therapy. Overall, the risk of ADA development was significantly higher in patients on cephalosporins (adjusted hazard ratio, 1.97; 95% confidence interval, 1.58-2.44) or penicillin with beta-lactamase inhibitors (BLIs) (aHR, 1.38; 95% CI, 1.13-1.74) during anti-TNF therapy, and it was higher still for patients using both. By contrast, the risk was lower in patients on macrolides (aHR, 0.36; 95% CI, 0.16-0.82) or fluoroquinolones (aHR, 0.20; 95% CI; 95% CI, 0.12-0.35). All P values were less than .05 when compared with nontreated groups.

In the same study, the researchers reported data on mice treated with antibiotics and challenged with infliximab to evaluate the causative effect of antibiotics and the associated disruption to the gut microbiome on the formation of ADA. After 14 days, the researchers found significantly increased ADA production in mice treated with cephalosporins, compared with those treated with macrolides, but germ-free mice produced no ADA, which supports the role of microbial composition on ADA production.

The investigators cited previous research into the microbiome as a biomarker for prediction response to anti-TNF therapy; past results have also suggested that the effect of cephalosporins and penicillin-BLIs could be explained by the particular dysbiosis induced by those agents.

The study findings were limited by several factors including the retrospective design and potential for selection bias, as well as the inability to adjust antibiotic exposure according to type and severity of infection, they noted. However, “this is the first large scale study that extensively evaluated the effect of different antibiotic classes on immunogenicity of anti-TNF therapy,” and the results suggest that ADA development during anti-TNF therapy may to reduced by the use of fluoroquinolones and macrolides.

“Specific microbial manipulation may serve as a tool to modify immunogenicity which is preferably turned on for protective immunizations and off for biological therapy,” they noted. “Further studies involving detailed analysis of the antibiotic effects on the human microbiome and immune milieu are needed, as well as comparative experiments with other medications used to reduce immunogenicity.”
 

Unexpected findings may drive future drug choices

“Development of antidrug antibodies in patients on biologics for inflammatory bowel disease is an important mechanism for loss of response to a therapeutic agent,” Kim L. Isaacs, MD, AGAF, of the University of North Carolina at Chapel Hill, said in an interview. “To date the causes of development of ADAs is relatively understudied. Our approach to prevent ADA includes increasing immunosuppression in patients most commonly with combination therapy with thiopurines. If factors that provoke or prevent antibody formation are elucidated, therapy can be tailored to prevent ADAs and maximize the duration of response of many of our biologic therapies.”

A prior study performed by the ABIRISK European consortium demonstrated associations with antibiotics. “In this study, there was a differential effect of cephalosporins/penicillins (increased immunogenicity) and macrolides (decreased immunogenicity),” she said. “These studies suggest that the microbiome may be important in ADA formation to biologics – this is a concept that is novel and unexpected.

“The rationale for the choice of antibiotics in the population studied is not known, and it is possible that different infections may have led to different antibiotic choices, which in turn may have affected immunogenicity,” said Dr. Isaacs. However, clinicians might be able to tailor antibiotic choice in the future if the microbiome is playing a major role in risk for development of ADA.

“Further research is needed to further correlate microbiome changes with immunogenicity, to look at other classes of antibiotics and their role in immunogenicity, and to clarify the infections or reasons that these patients are receiving antibiotics,” Dr. Isaacs concluded.
 

Understanding the microbiome

Recent observations have shown associations between clinical response to anti-TNF and gut microbiota composition, noted Jatin Roper, MD, of Duke University, Durham, N.C. “More broadly, a growing body of evidence suggests that the gut microbiota modulates the metabolism of many therapeutic agents, as well as immune responses to infections.”

That said, Dr. Roper was surprised that “clinical use of different antibiotics, often short term, had such distinct effects on ADA levels.” Furthermore, “these findings suggest that distinct microbiota or microbial metabolic products impact antibody development to common immunomodulatory therapies in opposite ways,” which is itself a surprising finding.

Such antibodies to anti-TNF therapy are common in IBD, he said, but one implication of the study is how antibiotics could be carefully used "to reduce risk of ADAs and enhance efficacy of anti-TNF therapy."

However, because any antibiotic therapy will modify the gut microbiome and lead to unwanted effects, “further research is needed on how these agents impact the gut microbiome, with the ultimate goal of identifying specific microbiota or microbial metabolic products that can reproduce the intriguing findings of this paper.”

The study was supported in part by the Leona M. and Harry B. Helmsley Charitable Trust and the Israeli Ministry of Science and Technology. Dr. Gorelik had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple pharmaceutical companies including AbbVie, CytoReason, Takeda, and Pfizer. Dr. Isaacs had no financial conflicts to disclose, but serves on the GI&Hepatology News board of editors. Dr. Roper had no relevant disclosures.

The use fluoroquinolones or macrolides reduced immunogenicity risk in inflammatory bowel disease (IBD) patients on anti–tumor necrosis factor (anti-TNF) therapy, according to data from nearly 2,000 individuals.

luchschen/Thinkstock

Anti-TNF therapy with monoclonal antibodies is an established treatment for Crohn’s disease and ulcerative colitis, but approximately 40% of patients fail to respond initially and even more fail to achieve complete remission, wrote Yuri Gorelik, MD, of Rambam Health Care Campus, Haifa, Israel, and colleagues.

“Immunogenicity, which refers to the development of antidrug antibodies [ADA] is considered as the main factor driving secondary loss of response and is likely involved in primary nonresponse as well,” but data on how to predict the risk for ADA formation are limited, they said.

In a study published in Gut, the researchers identified data from 1,946 IBD patients using the epi-IIRN (epidemiology group of the Israeli IBD research nucleus), a nationwide registry of all IBD patients in Israel.

A total of 363 patients had positive ADA after a median follow-up period of 651 days after starting therapy. Overall, the risk of ADA development was significantly higher in patients on cephalosporins (adjusted hazard ratio, 1.97; 95% confidence interval, 1.58-2.44) or penicillin with beta-lactamase inhibitors (BLIs) (aHR, 1.38; 95% CI, 1.13-1.74) during anti-TNF therapy, and it was higher still for patients using both. By contrast, the risk was lower in patients on macrolides (aHR, 0.36; 95% CI, 0.16-0.82) or fluoroquinolones (aHR, 0.20; 95% CI; 95% CI, 0.12-0.35). All P values were less than .05 when compared with nontreated groups.

In the same study, the researchers reported data on mice treated with antibiotics and challenged with infliximab to evaluate the causative effect of antibiotics and the associated disruption to the gut microbiome on the formation of ADA. After 14 days, the researchers found significantly increased ADA production in mice treated with cephalosporins, compared with those treated with macrolides, but germ-free mice produced no ADA, which supports the role of microbial composition on ADA production.

The investigators cited previous research into the microbiome as a biomarker for prediction response to anti-TNF therapy; past results have also suggested that the effect of cephalosporins and penicillin-BLIs could be explained by the particular dysbiosis induced by those agents.

The study findings were limited by several factors including the retrospective design and potential for selection bias, as well as the inability to adjust antibiotic exposure according to type and severity of infection, they noted. However, “this is the first large scale study that extensively evaluated the effect of different antibiotic classes on immunogenicity of anti-TNF therapy,” and the results suggest that ADA development during anti-TNF therapy may to reduced by the use of fluoroquinolones and macrolides.

“Specific microbial manipulation may serve as a tool to modify immunogenicity which is preferably turned on for protective immunizations and off for biological therapy,” they noted. “Further studies involving detailed analysis of the antibiotic effects on the human microbiome and immune milieu are needed, as well as comparative experiments with other medications used to reduce immunogenicity.”
 

Unexpected findings may drive future drug choices

“Development of antidrug antibodies in patients on biologics for inflammatory bowel disease is an important mechanism for loss of response to a therapeutic agent,” Kim L. Isaacs, MD, AGAF, of the University of North Carolina at Chapel Hill, said in an interview. “To date the causes of development of ADAs is relatively understudied. Our approach to prevent ADA includes increasing immunosuppression in patients most commonly with combination therapy with thiopurines. If factors that provoke or prevent antibody formation are elucidated, therapy can be tailored to prevent ADAs and maximize the duration of response of many of our biologic therapies.”

A prior study performed by the ABIRISK European consortium demonstrated associations with antibiotics. “In this study, there was a differential effect of cephalosporins/penicillins (increased immunogenicity) and macrolides (decreased immunogenicity),” she said. “These studies suggest that the microbiome may be important in ADA formation to biologics – this is a concept that is novel and unexpected.

“The rationale for the choice of antibiotics in the population studied is not known, and it is possible that different infections may have led to different antibiotic choices, which in turn may have affected immunogenicity,” said Dr. Isaacs. However, clinicians might be able to tailor antibiotic choice in the future if the microbiome is playing a major role in risk for development of ADA.

“Further research is needed to further correlate microbiome changes with immunogenicity, to look at other classes of antibiotics and their role in immunogenicity, and to clarify the infections or reasons that these patients are receiving antibiotics,” Dr. Isaacs concluded.
 

Understanding the microbiome

Recent observations have shown associations between clinical response to anti-TNF and gut microbiota composition, noted Jatin Roper, MD, of Duke University, Durham, N.C. “More broadly, a growing body of evidence suggests that the gut microbiota modulates the metabolism of many therapeutic agents, as well as immune responses to infections.”

That said, Dr. Roper was surprised that “clinical use of different antibiotics, often short term, had such distinct effects on ADA levels.” Furthermore, “these findings suggest that distinct microbiota or microbial metabolic products impact antibody development to common immunomodulatory therapies in opposite ways,” which is itself a surprising finding.

Such antibodies to anti-TNF therapy are common in IBD, he said, but one implication of the study is how antibiotics could be carefully used "to reduce risk of ADAs and enhance efficacy of anti-TNF therapy."

However, because any antibiotic therapy will modify the gut microbiome and lead to unwanted effects, “further research is needed on how these agents impact the gut microbiome, with the ultimate goal of identifying specific microbiota or microbial metabolic products that can reproduce the intriguing findings of this paper.”

The study was supported in part by the Leona M. and Harry B. Helmsley Charitable Trust and the Israeli Ministry of Science and Technology. Dr. Gorelik had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple pharmaceutical companies including AbbVie, CytoReason, Takeda, and Pfizer. Dr. Isaacs had no financial conflicts to disclose, but serves on the GI&Hepatology News board of editors. Dr. Roper had no relevant disclosures.

The use fluoroquinolones or macrolides reduced immunogenicity risk in inflammatory bowel disease (IBD) patients on anti–tumor necrosis factor (anti-TNF) therapy, according to data from nearly 2,000 individuals.

luchschen/Thinkstock

Anti-TNF therapy with monoclonal antibodies is an established treatment for Crohn’s disease and ulcerative colitis, but approximately 40% of patients fail to respond initially and even more fail to achieve complete remission, wrote Yuri Gorelik, MD, of Rambam Health Care Campus, Haifa, Israel, and colleagues.

“Immunogenicity, which refers to the development of antidrug antibodies [ADA] is considered as the main factor driving secondary loss of response and is likely involved in primary nonresponse as well,” but data on how to predict the risk for ADA formation are limited, they said.

In a study published in Gut, the researchers identified data from 1,946 IBD patients using the epi-IIRN (epidemiology group of the Israeli IBD research nucleus), a nationwide registry of all IBD patients in Israel.

A total of 363 patients had positive ADA after a median follow-up period of 651 days after starting therapy. Overall, the risk of ADA development was significantly higher in patients on cephalosporins (adjusted hazard ratio, 1.97; 95% confidence interval, 1.58-2.44) or penicillin with beta-lactamase inhibitors (BLIs) (aHR, 1.38; 95% CI, 1.13-1.74) during anti-TNF therapy, and it was higher still for patients using both. By contrast, the risk was lower in patients on macrolides (aHR, 0.36; 95% CI, 0.16-0.82) or fluoroquinolones (aHR, 0.20; 95% CI; 95% CI, 0.12-0.35). All P values were less than .05 when compared with nontreated groups.

In the same study, the researchers reported data on mice treated with antibiotics and challenged with infliximab to evaluate the causative effect of antibiotics and the associated disruption to the gut microbiome on the formation of ADA. After 14 days, the researchers found significantly increased ADA production in mice treated with cephalosporins, compared with those treated with macrolides, but germ-free mice produced no ADA, which supports the role of microbial composition on ADA production.

The investigators cited previous research into the microbiome as a biomarker for prediction response to anti-TNF therapy; past results have also suggested that the effect of cephalosporins and penicillin-BLIs could be explained by the particular dysbiosis induced by those agents.

The study findings were limited by several factors including the retrospective design and potential for selection bias, as well as the inability to adjust antibiotic exposure according to type and severity of infection, they noted. However, “this is the first large scale study that extensively evaluated the effect of different antibiotic classes on immunogenicity of anti-TNF therapy,” and the results suggest that ADA development during anti-TNF therapy may to reduced by the use of fluoroquinolones and macrolides.

“Specific microbial manipulation may serve as a tool to modify immunogenicity which is preferably turned on for protective immunizations and off for biological therapy,” they noted. “Further studies involving detailed analysis of the antibiotic effects on the human microbiome and immune milieu are needed, as well as comparative experiments with other medications used to reduce immunogenicity.”
 

Unexpected findings may drive future drug choices

“Development of antidrug antibodies in patients on biologics for inflammatory bowel disease is an important mechanism for loss of response to a therapeutic agent,” Kim L. Isaacs, MD, AGAF, of the University of North Carolina at Chapel Hill, said in an interview. “To date the causes of development of ADAs is relatively understudied. Our approach to prevent ADA includes increasing immunosuppression in patients most commonly with combination therapy with thiopurines. If factors that provoke or prevent antibody formation are elucidated, therapy can be tailored to prevent ADAs and maximize the duration of response of many of our biologic therapies.”

A prior study performed by the ABIRISK European consortium demonstrated associations with antibiotics. “In this study, there was a differential effect of cephalosporins/penicillins (increased immunogenicity) and macrolides (decreased immunogenicity),” she said. “These studies suggest that the microbiome may be important in ADA formation to biologics – this is a concept that is novel and unexpected.

“The rationale for the choice of antibiotics in the population studied is not known, and it is possible that different infections may have led to different antibiotic choices, which in turn may have affected immunogenicity,” said Dr. Isaacs. However, clinicians might be able to tailor antibiotic choice in the future if the microbiome is playing a major role in risk for development of ADA.

“Further research is needed to further correlate microbiome changes with immunogenicity, to look at other classes of antibiotics and their role in immunogenicity, and to clarify the infections or reasons that these patients are receiving antibiotics,” Dr. Isaacs concluded.
 

Understanding the microbiome

Recent observations have shown associations between clinical response to anti-TNF and gut microbiota composition, noted Jatin Roper, MD, of Duke University, Durham, N.C. “More broadly, a growing body of evidence suggests that the gut microbiota modulates the metabolism of many therapeutic agents, as well as immune responses to infections.”

That said, Dr. Roper was surprised that “clinical use of different antibiotics, often short term, had such distinct effects on ADA levels.” Furthermore, “these findings suggest that distinct microbiota or microbial metabolic products impact antibody development to common immunomodulatory therapies in opposite ways,” which is itself a surprising finding.

Such antibodies to anti-TNF therapy are common in IBD, he said, but one implication of the study is how antibiotics could be carefully used "to reduce risk of ADAs and enhance efficacy of anti-TNF therapy."

However, because any antibiotic therapy will modify the gut microbiome and lead to unwanted effects, “further research is needed on how these agents impact the gut microbiome, with the ultimate goal of identifying specific microbiota or microbial metabolic products that can reproduce the intriguing findings of this paper.”

The study was supported in part by the Leona M. and Harry B. Helmsley Charitable Trust and the Israeli Ministry of Science and Technology. Dr. Gorelik had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple pharmaceutical companies including AbbVie, CytoReason, Takeda, and Pfizer. Dr. Isaacs had no financial conflicts to disclose, but serves on the GI&Hepatology News board of editors. Dr. Roper had no relevant disclosures.

Structural racism and implicit bias are connected, and both must be addressed to move from awareness of racism to action, said Nathan Chomilo, MD, of HealthPartners/Park Nicollet, Brooklyn Center, Minn., in a presentation at the virtual Pediatric Hospital Medicine annual conference.

“We need pediatricians with the courage to address racism head on,” he said.

One step in moving from awareness to action against structural and institutional racism in medicine is examining policies, Dr. Chomilo said. He cited the creation of Medicare and Medicaid in 1965 as examples of how policy changes can make a difference, illustrated by data from 1955-1975 that showed a significant decrease in infant deaths among Black infants in Mississippi after 1965.

Medicaid expansion has helped to narrow, but not eliminate, racial disparities in health care, Dr. Chomilo said. The impact of Medicare and Medicaid is evident in the current COVID-19 pandemic, as county level data show that areas where more than 25% of the population are uninsured have higher rates of COVID-19 infections, said Dr. Chomilo. Policies that impact access to care also impact their incidence of chronic diseases and risk for severe disease, he noted.

“If you don’t have ready access to a health care provider, you don’t have access to the vaccine, and you don’t have information that would inform your getting the vaccine,” he added.
 

Prioritizing the power of voting

“Voting is one of many ways we can impact structural racism in health care policy,” Dr. Chomilo emphasized.

However, voting inequity remains a challenge, Dr. Chomilo noted. Community level disparities lead to inequity in voting access and subsequent disparities in voter participation, he said. “Leaders are less responsive to nonvoting constituents,” which can result in policies that impact health inequitably, and loop back to community level health disparities, he explained.

Historically, physicians have had an 8%-9% lower voter turnout than the general public, although this may have changed in recent elections, Dr. Chomilo said. He encouraged all clinicians to set an example and vote, and to empower their patients to vote. Evidence shows that enfranchisement of Black voters is associated with reductions in education gaps for Blacks and Whites, and that enfranchisement of women is associated with increased spending on children and lower child mortality, he said. Dr. Chomilo encouraged pediatricians and all clinicians to take advantage of the resources on voting available from the American Academy of Pediatrics (aap.org/votekids).

“When we see more people in a community vote, leaders are more responsive to their needs,” he said.
 

Informing racial identity

“Racial identity is informed by racial socialization,” Dr. Chomilo said. “All of us are socialized along the lines of race; it happens in conversations with parents, family, peers, community.” Another point in moving from awareness to action in eliminating structural racism is recognizing that children are not too young to talk about race, Dr. Chomilo emphasized.

Children start to navigate racial identity and to take note of other differences at an early age. For example, a 3-year-old might ask, “why does that person talk funny, why is that person being pushed in a chair?” Dr. Chomilo said, and it is important for parents and as pediatricians to be prepared for these questions, which are part of normal development. As children get older, they start to reflect on what differences mean for them, which is not rooted in anything negative, he noted.

Children first develop racial identity at home, but children solidify their identities in child care and school settings, Dr. Chomilo said. The American Academy of Pediatrics has acknowledged the potential for racial bias in education and child care, and said in a statement that, “it is critical for pediatricians to recognize the institutional personally mediated, and internalized levels of racism that occur in the educational setting, because education is a critical social determinant of health for children.” In fact, data from children in preschool show that they use racial categories to identify themselves and others, to include or exclude children from activities, and to negotiate power in their social and play networks.

Early intervention matters in educating children about racism, Dr. Chomilo said. “If we were not taught to talk about race, it is on us to learn about it ourselves as well,” he said.

Ultimately, the goal is to create active antiracism among adults and children, said Dr. Chomilo. He encouraged pediatricians and parents not to shut down or discourage children when they raise questions of race, but to take the opportunity to teach. “There may be hurt feelings around what a child said, even if they didn’t mean to offend someone,” he noted. Take the topic seriously, and make racism conversations ongoing; teach children to safely oppose negative messages and behaviors in others, and replace them with something positive, he emphasized.
 

Addressing bias in clinical settings

Dr. Chomilo also encouraged hospitalists to consider internalized racism in clinical settings and take action to build confidence and cultural pride in all patients by ensuring that a pediatric hospital unit is welcoming and representative of the diversity in a given community, with appropriate options for books, movies, and toys. He also encouraged pediatric hospitalists to assess children for experiences of racism as part of a social assessment. Be aware of signs of posttraumatic stress, anxiety, depression, or grief that might have a racial component, he said.

Dr. Chomilo had no financial conflicts to disclose.

Structural racism and implicit bias are connected, and both must be addressed to move from awareness of racism to action, said Nathan Chomilo, MD, of HealthPartners/Park Nicollet, Brooklyn Center, Minn., in a presentation at the virtual Pediatric Hospital Medicine annual conference.

“We need pediatricians with the courage to address racism head on,” he said.

One step in moving from awareness to action against structural and institutional racism in medicine is examining policies, Dr. Chomilo said. He cited the creation of Medicare and Medicaid in 1965 as examples of how policy changes can make a difference, illustrated by data from 1955-1975 that showed a significant decrease in infant deaths among Black infants in Mississippi after 1965.

Medicaid expansion has helped to narrow, but not eliminate, racial disparities in health care, Dr. Chomilo said. The impact of Medicare and Medicaid is evident in the current COVID-19 pandemic, as county level data show that areas where more than 25% of the population are uninsured have higher rates of COVID-19 infections, said Dr. Chomilo. Policies that impact access to care also impact their incidence of chronic diseases and risk for severe disease, he noted.

“If you don’t have ready access to a health care provider, you don’t have access to the vaccine, and you don’t have information that would inform your getting the vaccine,” he added.
 

Prioritizing the power of voting

“Voting is one of many ways we can impact structural racism in health care policy,” Dr. Chomilo emphasized.

However, voting inequity remains a challenge, Dr. Chomilo noted. Community level disparities lead to inequity in voting access and subsequent disparities in voter participation, he said. “Leaders are less responsive to nonvoting constituents,” which can result in policies that impact health inequitably, and loop back to community level health disparities, he explained.

Historically, physicians have had an 8%-9% lower voter turnout than the general public, although this may have changed in recent elections, Dr. Chomilo said. He encouraged all clinicians to set an example and vote, and to empower their patients to vote. Evidence shows that enfranchisement of Black voters is associated with reductions in education gaps for Blacks and Whites, and that enfranchisement of women is associated with increased spending on children and lower child mortality, he said. Dr. Chomilo encouraged pediatricians and all clinicians to take advantage of the resources on voting available from the American Academy of Pediatrics (aap.org/votekids).

“When we see more people in a community vote, leaders are more responsive to their needs,” he said.
 

Informing racial identity

“Racial identity is informed by racial socialization,” Dr. Chomilo said. “All of us are socialized along the lines of race; it happens in conversations with parents, family, peers, community.” Another point in moving from awareness to action in eliminating structural racism is recognizing that children are not too young to talk about race, Dr. Chomilo emphasized.

Children start to navigate racial identity and to take note of other differences at an early age. For example, a 3-year-old might ask, “why does that person talk funny, why is that person being pushed in a chair?” Dr. Chomilo said, and it is important for parents and as pediatricians to be prepared for these questions, which are part of normal development. As children get older, they start to reflect on what differences mean for them, which is not rooted in anything negative, he noted.

Children first develop racial identity at home, but children solidify their identities in child care and school settings, Dr. Chomilo said. The American Academy of Pediatrics has acknowledged the potential for racial bias in education and child care, and said in a statement that, “it is critical for pediatricians to recognize the institutional personally mediated, and internalized levels of racism that occur in the educational setting, because education is a critical social determinant of health for children.” In fact, data from children in preschool show that they use racial categories to identify themselves and others, to include or exclude children from activities, and to negotiate power in their social and play networks.

Early intervention matters in educating children about racism, Dr. Chomilo said. “If we were not taught to talk about race, it is on us to learn about it ourselves as well,” he said.

Ultimately, the goal is to create active antiracism among adults and children, said Dr. Chomilo. He encouraged pediatricians and parents not to shut down or discourage children when they raise questions of race, but to take the opportunity to teach. “There may be hurt feelings around what a child said, even if they didn’t mean to offend someone,” he noted. Take the topic seriously, and make racism conversations ongoing; teach children to safely oppose negative messages and behaviors in others, and replace them with something positive, he emphasized.
 

Addressing bias in clinical settings

Dr. Chomilo also encouraged hospitalists to consider internalized racism in clinical settings and take action to build confidence and cultural pride in all patients by ensuring that a pediatric hospital unit is welcoming and representative of the diversity in a given community, with appropriate options for books, movies, and toys. He also encouraged pediatric hospitalists to assess children for experiences of racism as part of a social assessment. Be aware of signs of posttraumatic stress, anxiety, depression, or grief that might have a racial component, he said.

Dr. Chomilo had no financial conflicts to disclose.

Structural racism and implicit bias are connected, and both must be addressed to move from awareness of racism to action, said Nathan Chomilo, MD, of HealthPartners/Park Nicollet, Brooklyn Center, Minn., in a presentation at the virtual Pediatric Hospital Medicine annual conference.

“We need pediatricians with the courage to address racism head on,” he said.

One step in moving from awareness to action against structural and institutional racism in medicine is examining policies, Dr. Chomilo said. He cited the creation of Medicare and Medicaid in 1965 as examples of how policy changes can make a difference, illustrated by data from 1955-1975 that showed a significant decrease in infant deaths among Black infants in Mississippi after 1965.

Medicaid expansion has helped to narrow, but not eliminate, racial disparities in health care, Dr. Chomilo said. The impact of Medicare and Medicaid is evident in the current COVID-19 pandemic, as county level data show that areas where more than 25% of the population are uninsured have higher rates of COVID-19 infections, said Dr. Chomilo. Policies that impact access to care also impact their incidence of chronic diseases and risk for severe disease, he noted.

“If you don’t have ready access to a health care provider, you don’t have access to the vaccine, and you don’t have information that would inform your getting the vaccine,” he added.
 

Prioritizing the power of voting

“Voting is one of many ways we can impact structural racism in health care policy,” Dr. Chomilo emphasized.

However, voting inequity remains a challenge, Dr. Chomilo noted. Community level disparities lead to inequity in voting access and subsequent disparities in voter participation, he said. “Leaders are less responsive to nonvoting constituents,” which can result in policies that impact health inequitably, and loop back to community level health disparities, he explained.

Historically, physicians have had an 8%-9% lower voter turnout than the general public, although this may have changed in recent elections, Dr. Chomilo said. He encouraged all clinicians to set an example and vote, and to empower their patients to vote. Evidence shows that enfranchisement of Black voters is associated with reductions in education gaps for Blacks and Whites, and that enfranchisement of women is associated with increased spending on children and lower child mortality, he said. Dr. Chomilo encouraged pediatricians and all clinicians to take advantage of the resources on voting available from the American Academy of Pediatrics (aap.org/votekids).

“When we see more people in a community vote, leaders are more responsive to their needs,” he said.
 

Informing racial identity

“Racial identity is informed by racial socialization,” Dr. Chomilo said. “All of us are socialized along the lines of race; it happens in conversations with parents, family, peers, community.” Another point in moving from awareness to action in eliminating structural racism is recognizing that children are not too young to talk about race, Dr. Chomilo emphasized.

Children start to navigate racial identity and to take note of other differences at an early age. For example, a 3-year-old might ask, “why does that person talk funny, why is that person being pushed in a chair?” Dr. Chomilo said, and it is important for parents and as pediatricians to be prepared for these questions, which are part of normal development. As children get older, they start to reflect on what differences mean for them, which is not rooted in anything negative, he noted.

Children first develop racial identity at home, but children solidify their identities in child care and school settings, Dr. Chomilo said. The American Academy of Pediatrics has acknowledged the potential for racial bias in education and child care, and said in a statement that, “it is critical for pediatricians to recognize the institutional personally mediated, and internalized levels of racism that occur in the educational setting, because education is a critical social determinant of health for children.” In fact, data from children in preschool show that they use racial categories to identify themselves and others, to include or exclude children from activities, and to negotiate power in their social and play networks.

Early intervention matters in educating children about racism, Dr. Chomilo said. “If we were not taught to talk about race, it is on us to learn about it ourselves as well,” he said.

Ultimately, the goal is to create active antiracism among adults and children, said Dr. Chomilo. He encouraged pediatricians and parents not to shut down or discourage children when they raise questions of race, but to take the opportunity to teach. “There may be hurt feelings around what a child said, even if they didn’t mean to offend someone,” he noted. Take the topic seriously, and make racism conversations ongoing; teach children to safely oppose negative messages and behaviors in others, and replace them with something positive, he emphasized.
 

Addressing bias in clinical settings

Dr. Chomilo also encouraged hospitalists to consider internalized racism in clinical settings and take action to build confidence and cultural pride in all patients by ensuring that a pediatric hospital unit is welcoming and representative of the diversity in a given community, with appropriate options for books, movies, and toys. He also encouraged pediatric hospitalists to assess children for experiences of racism as part of a social assessment. Be aware of signs of posttraumatic stress, anxiety, depression, or grief that might have a racial component, he said.

Dr. Chomilo had no financial conflicts to disclose.