Conference Coverage

System-level changes to the way cancer care is delivered can help eliminate survival disparities between Black and White patients.

When barriers to completing radiation therapy were identified and addressed in a cohort of patients with early-stage lung and breast cancer, 5-year survival rates improved for all patients and closed the racial disparity gap, researchers reported at the annual meeting of the American Society for Radiation Oncology (ASTRO).

The findings come from the ACCURE clinical trial. This is the first prospective study designed to erase gaps in cancer treatment completion and survival among Black and White patient populations, explained lead author Matthew A. Manning, MD, a radiation oncologist and chief of oncology at Cone Health in Greensboro, N.C.

“Thousands of studies have looked at racial disparities in health care, but until recently, very few studies have implemented interventions to eliminate those disparities,” he said.

“This study shows that the implementation of ‘systems-change’ can eliminate racial disparities in cancer survival while improving survival for all,” he added.

“These results add to a growing body of evidence that health care disparities in cancer outcomes are eliminated or minimized by providing supportive, timely, and guideline-directed care,” said Lannis Hall, MD, MPH, director of radiation oncology, Siteman Cancer Center, and associate professor of radiation oncology at Washington University School of Medicine, St. Louis, who was approached for comment

“This research supports that access to care and timely treatment completion is critical to eliminating health care disparities,” she told this news organization. The system-based intervention in this trial was designed to reduce treatment delays and provide a supportive matrix for patients confronting real-world difficulties like transportation issues, childcare complications, and work absence, she explained.
 

Eliminating racial disparities

Previous findings from the ACCURE trial showed that it eliminated Black-White disparities in treatment completion rates, which was the study’s primary endpoint (Cancer Med. 2019;8:1095-1102). “It also improved treatment for all patients,” said Dr. Manning. “The current study is a follow-up on the survival of eligible patients treated during the ACCURE enrollment as compared to historical data.”

ACCURE was a multi-institutional trial designed to test a community-created intervention to reduce racial disparities. The intervention involved multiple changes to the way patients were supported while receiving cancer treatment and had four components: 

• an electronic health record with automatic alerts to flag missed appointments or unmet milestones in expected care 
• a nurse navigator trained in race-specific barriers to help patients overcome obstacles to care when alerts are flagged
• a physician champion to engage health care teams with race-related feedback on treatment completion
• regular health equity education training sessions for staff

The cohort was comprised of 1,413 patients with lung and breast cancer (stage 0-II) who were diagnosed from 2013-2015, and survival was compared to historical cases – 2,016 patients who had been treated from 2007-2011.

The results showed a significant improvement in survival for both Black and White patients with breast and lung cancer over time, and the racial gap in survival was reduced. 

The 5-year survival rate for breast cancer increased from 91% for White patients and 89% in Black patients in historical cases, to 94% for both during the study period.  

For patients with lung cancer, the 5-year survival rate improved from 43% in White patients and 37% in Black patients to 56% and 54%, respectively.

A subgroup analysis showed that patients with lung cancer who underwent surgery had 5-year survival rates of 78.5% for White and 70.1% for Black patients, whereas for those who underwent stereotactic body radiation therapy (SBRT) the rates were 41.9% and 50% respectively.

“We’ve shown it’s possible to eliminate disparities in cancer treatment completion and that this change has the potential to close cancer survival gaps downstream,” said Dr. Manning. “But we think the application can be much broader.” 

The ACCURE study was sponsored by the National Institutes of Health. Dr. Manning and Dr. Hall have disclosed no relevant financial relationships.

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

System-level changes to the way cancer care is delivered can help eliminate survival disparities between Black and White patients.

When barriers to completing radiation therapy were identified and addressed in a cohort of patients with early-stage lung and breast cancer, 5-year survival rates improved for all patients and closed the racial disparity gap, researchers reported at the annual meeting of the American Society for Radiation Oncology (ASTRO).

The findings come from the ACCURE clinical trial. This is the first prospective study designed to erase gaps in cancer treatment completion and survival among Black and White patient populations, explained lead author Matthew A. Manning, MD, a radiation oncologist and chief of oncology at Cone Health in Greensboro, N.C.

“Thousands of studies have looked at racial disparities in health care, but until recently, very few studies have implemented interventions to eliminate those disparities,” he said.

“This study shows that the implementation of ‘systems-change’ can eliminate racial disparities in cancer survival while improving survival for all,” he added.

“These results add to a growing body of evidence that health care disparities in cancer outcomes are eliminated or minimized by providing supportive, timely, and guideline-directed care,” said Lannis Hall, MD, MPH, director of radiation oncology, Siteman Cancer Center, and associate professor of radiation oncology at Washington University School of Medicine, St. Louis, who was approached for comment

“This research supports that access to care and timely treatment completion is critical to eliminating health care disparities,” she told this news organization. The system-based intervention in this trial was designed to reduce treatment delays and provide a supportive matrix for patients confronting real-world difficulties like transportation issues, childcare complications, and work absence, she explained.
 

Eliminating racial disparities

Previous findings from the ACCURE trial showed that it eliminated Black-White disparities in treatment completion rates, which was the study’s primary endpoint (Cancer Med. 2019;8:1095-1102). “It also improved treatment for all patients,” said Dr. Manning. “The current study is a follow-up on the survival of eligible patients treated during the ACCURE enrollment as compared to historical data.”

ACCURE was a multi-institutional trial designed to test a community-created intervention to reduce racial disparities. The intervention involved multiple changes to the way patients were supported while receiving cancer treatment and had four components: 

• an electronic health record with automatic alerts to flag missed appointments or unmet milestones in expected care 
• a nurse navigator trained in race-specific barriers to help patients overcome obstacles to care when alerts are flagged
• a physician champion to engage health care teams with race-related feedback on treatment completion
• regular health equity education training sessions for staff

The cohort was comprised of 1,413 patients with lung and breast cancer (stage 0-II) who were diagnosed from 2013-2015, and survival was compared to historical cases – 2,016 patients who had been treated from 2007-2011.

The results showed a significant improvement in survival for both Black and White patients with breast and lung cancer over time, and the racial gap in survival was reduced. 

The 5-year survival rate for breast cancer increased from 91% for White patients and 89% in Black patients in historical cases, to 94% for both during the study period.  

For patients with lung cancer, the 5-year survival rate improved from 43% in White patients and 37% in Black patients to 56% and 54%, respectively.

A subgroup analysis showed that patients with lung cancer who underwent surgery had 5-year survival rates of 78.5% for White and 70.1% for Black patients, whereas for those who underwent stereotactic body radiation therapy (SBRT) the rates were 41.9% and 50% respectively.

“We’ve shown it’s possible to eliminate disparities in cancer treatment completion and that this change has the potential to close cancer survival gaps downstream,” said Dr. Manning. “But we think the application can be much broader.” 

The ACCURE study was sponsored by the National Institutes of Health. Dr. Manning and Dr. Hall have disclosed no relevant financial relationships.

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

System-level changes to the way cancer care is delivered can help eliminate survival disparities between Black and White patients.

When barriers to completing radiation therapy were identified and addressed in a cohort of patients with early-stage lung and breast cancer, 5-year survival rates improved for all patients and closed the racial disparity gap, researchers reported at the annual meeting of the American Society for Radiation Oncology (ASTRO).

The findings come from the ACCURE clinical trial. This is the first prospective study designed to erase gaps in cancer treatment completion and survival among Black and White patient populations, explained lead author Matthew A. Manning, MD, a radiation oncologist and chief of oncology at Cone Health in Greensboro, N.C.

“Thousands of studies have looked at racial disparities in health care, but until recently, very few studies have implemented interventions to eliminate those disparities,” he said.

“This study shows that the implementation of ‘systems-change’ can eliminate racial disparities in cancer survival while improving survival for all,” he added.

“These results add to a growing body of evidence that health care disparities in cancer outcomes are eliminated or minimized by providing supportive, timely, and guideline-directed care,” said Lannis Hall, MD, MPH, director of radiation oncology, Siteman Cancer Center, and associate professor of radiation oncology at Washington University School of Medicine, St. Louis, who was approached for comment

“This research supports that access to care and timely treatment completion is critical to eliminating health care disparities,” she told this news organization. The system-based intervention in this trial was designed to reduce treatment delays and provide a supportive matrix for patients confronting real-world difficulties like transportation issues, childcare complications, and work absence, she explained.
 

Eliminating racial disparities

Previous findings from the ACCURE trial showed that it eliminated Black-White disparities in treatment completion rates, which was the study’s primary endpoint (Cancer Med. 2019;8:1095-1102). “It also improved treatment for all patients,” said Dr. Manning. “The current study is a follow-up on the survival of eligible patients treated during the ACCURE enrollment as compared to historical data.”

ACCURE was a multi-institutional trial designed to test a community-created intervention to reduce racial disparities. The intervention involved multiple changes to the way patients were supported while receiving cancer treatment and had four components: 

• an electronic health record with automatic alerts to flag missed appointments or unmet milestones in expected care 
• a nurse navigator trained in race-specific barriers to help patients overcome obstacles to care when alerts are flagged
• a physician champion to engage health care teams with race-related feedback on treatment completion
• regular health equity education training sessions for staff

The cohort was comprised of 1,413 patients with lung and breast cancer (stage 0-II) who were diagnosed from 2013-2015, and survival was compared to historical cases – 2,016 patients who had been treated from 2007-2011.

The results showed a significant improvement in survival for both Black and White patients with breast and lung cancer over time, and the racial gap in survival was reduced. 

The 5-year survival rate for breast cancer increased from 91% for White patients and 89% in Black patients in historical cases, to 94% for both during the study period.  

For patients with lung cancer, the 5-year survival rate improved from 43% in White patients and 37% in Black patients to 56% and 54%, respectively.

A subgroup analysis showed that patients with lung cancer who underwent surgery had 5-year survival rates of 78.5% for White and 70.1% for Black patients, whereas for those who underwent stereotactic body radiation therapy (SBRT) the rates were 41.9% and 50% respectively.

“We’ve shown it’s possible to eliminate disparities in cancer treatment completion and that this change has the potential to close cancer survival gaps downstream,” said Dr. Manning. “But we think the application can be much broader.” 

The ACCURE study was sponsored by the National Institutes of Health. Dr. Manning and Dr. Hall have disclosed no relevant financial relationships.

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

Although genomic testing is useful when an interstitial lung disease diagnosis is uncertain, the testing results themselves aren’t sufficient to make the diagnosis, Daniel Dilling, MD, FCCP, said in a presentation at the annual meeting of the American College of Chest Physicians, which was held virtually.

The genomic classifier (Envisia, Veracyte) helps differentiate idiopathic pulmonary fibrosis (IPF) by detecting usual interstitial pneumonia (UIP), the hallmark pattern of this interstitial lung disease.

However, UIP is just one piece of the larger diagnostic puzzle, according to Dr. Dilling, professor of medicine in the interstitial lung disease program at Loyola University Medical Center in Maywood, Ill.

“Remember, it’s just a pattern, and not a diagnosis of IPF,” Dr. Dilling said in his presentation.

Genomic classifier results correlate well with both histologic and radiographic UIP pattern, studies show.

However, Dr. Dilling said the value of the genomic classifier is not in isolation.

“We don’t use this in a vacuum,” he said. “It increases our confidence and consensus, but it has to be incorporated into a multidisciplinary discussion group.”
 

Part of the diagnostic pathway

Dr. Dilling said the genomic classifier should be considered part of a diagnostic pathway in uncertain cases, particularly when the risk of surgical lung biopsy is high.

Current clinical practice guidelines recommend surgical lung biopsy for histopathologic diagnosis when clinical and radiologic findings are not definitive for IPF, the speaker said.

However, surgical lung biopsy carries some risk, and sometimes it can’t be done, he added.

In his presentation, Dr. Dilling cited a systematic review and meta-analysis of 23 studies looking at surgical lung biopsy for the diagnosis of interstitial lung diseases.

The postoperative mortality rate was 3.6% in that meta-analysis, published in 2015 in the Journal of Thoracic and Cardiovascular Surgery.

“The final decision regarding whether or not to perform a [surgical lung biopsy] must be based on the balance between benefits to establish a secure diagnosis and the potential risks,” authors wrote at the time.

Mortality risk is higher in immunocompromised and acutely ill patient populations, according to Dr. Dilling, who added that as many of 19% of patients will have complications from surgical lung biopsy.
 

Genomic classifier studies

In a proof-of-principle study, published in 2017 in the Annals of the American Thoracic Society, authors described how they used machine learning to train an algorithm to distinguish UIP from non-UIP pattern in tissue obtained by transbronchial biopsy (TBB).

The top-performing algorithm distinguished UIP from non-UIP conditions in single TBB samples with specificity of 86% and sensitivity of 63%, according to investigators, who said at the time that independent validation would be needed before the genomic classifier could be applied in clinical settings.

In a prospective validation study, published in 2019 in The Lancet Respiratory Medicine, the genomic classifier identified UIP in TBB samples from 49 patients with a specificity of 88% and sensitivity of 70%.

Excluding patients with definite or probable UIP as shown on high-resolution computed tomography, results show that the classifier had a sensitivity of 76%, specificity of 88%, and positive predictive value of 81%.

“The performance of the test is good, even in that scenario,” Dr. Dilling said.
 

Real-world results

Dr. Dilling also highlighted a “real-world” study, published earlier in 2021, demonstrating that UIP pattern recognized by a genomic classifier had encouraging sensitivity and specificity when combined with high-resolution CT and clinical factors.

That study included 96 patients who had both diagnostic lung pathology and a transbronchial lung biopsy for molecular testing with the classifier.

The classifier had a sensitivity of 60.3% and a specificity of 92.1% for histology-proven UIP pattern, investigators said in their report, which appears in the American Journal of Respiratory and Critical Care Medicine.

Local radiologists identified UIP with a sensitivity of 34.0% and specificity of 96.9%. But adding genomic classifier testing to local radiology testing increased the diagnostic yield, investigators said, with a sensitivity of 79.2% and specificity of 90.6%.

“This might suggest that the implementation of this into a local [multidisciplinary discussion] with your local radiology expertise might really improve your recognition of UIP,” Dr. Dilling said.

Dr. Dilling reported disclosures related to Bellerophon, Boehringer Ingelheim, Genentech, Nitto Denko, and Lung Bioengineering.

Although genomic testing is useful when an interstitial lung disease diagnosis is uncertain, the testing results themselves aren’t sufficient to make the diagnosis, Daniel Dilling, MD, FCCP, said in a presentation at the annual meeting of the American College of Chest Physicians, which was held virtually.

The genomic classifier (Envisia, Veracyte) helps differentiate idiopathic pulmonary fibrosis (IPF) by detecting usual interstitial pneumonia (UIP), the hallmark pattern of this interstitial lung disease.

However, UIP is just one piece of the larger diagnostic puzzle, according to Dr. Dilling, professor of medicine in the interstitial lung disease program at Loyola University Medical Center in Maywood, Ill.

“Remember, it’s just a pattern, and not a diagnosis of IPF,” Dr. Dilling said in his presentation.

Genomic classifier results correlate well with both histologic and radiographic UIP pattern, studies show.

However, Dr. Dilling said the value of the genomic classifier is not in isolation.

“We don’t use this in a vacuum,” he said. “It increases our confidence and consensus, but it has to be incorporated into a multidisciplinary discussion group.”
 

Part of the diagnostic pathway

Dr. Dilling said the genomic classifier should be considered part of a diagnostic pathway in uncertain cases, particularly when the risk of surgical lung biopsy is high.

Current clinical practice guidelines recommend surgical lung biopsy for histopathologic diagnosis when clinical and radiologic findings are not definitive for IPF, the speaker said.

However, surgical lung biopsy carries some risk, and sometimes it can’t be done, he added.

In his presentation, Dr. Dilling cited a systematic review and meta-analysis of 23 studies looking at surgical lung biopsy for the diagnosis of interstitial lung diseases.

The postoperative mortality rate was 3.6% in that meta-analysis, published in 2015 in the Journal of Thoracic and Cardiovascular Surgery.

“The final decision regarding whether or not to perform a [surgical lung biopsy] must be based on the balance between benefits to establish a secure diagnosis and the potential risks,” authors wrote at the time.

Mortality risk is higher in immunocompromised and acutely ill patient populations, according to Dr. Dilling, who added that as many of 19% of patients will have complications from surgical lung biopsy.
 

Genomic classifier studies

In a proof-of-principle study, published in 2017 in the Annals of the American Thoracic Society, authors described how they used machine learning to train an algorithm to distinguish UIP from non-UIP pattern in tissue obtained by transbronchial biopsy (TBB).

The top-performing algorithm distinguished UIP from non-UIP conditions in single TBB samples with specificity of 86% and sensitivity of 63%, according to investigators, who said at the time that independent validation would be needed before the genomic classifier could be applied in clinical settings.

In a prospective validation study, published in 2019 in The Lancet Respiratory Medicine, the genomic classifier identified UIP in TBB samples from 49 patients with a specificity of 88% and sensitivity of 70%.

Excluding patients with definite or probable UIP as shown on high-resolution computed tomography, results show that the classifier had a sensitivity of 76%, specificity of 88%, and positive predictive value of 81%.

“The performance of the test is good, even in that scenario,” Dr. Dilling said.
 

Real-world results

Dr. Dilling also highlighted a “real-world” study, published earlier in 2021, demonstrating that UIP pattern recognized by a genomic classifier had encouraging sensitivity and specificity when combined with high-resolution CT and clinical factors.

That study included 96 patients who had both diagnostic lung pathology and a transbronchial lung biopsy for molecular testing with the classifier.

The classifier had a sensitivity of 60.3% and a specificity of 92.1% for histology-proven UIP pattern, investigators said in their report, which appears in the American Journal of Respiratory and Critical Care Medicine.

Local radiologists identified UIP with a sensitivity of 34.0% and specificity of 96.9%. But adding genomic classifier testing to local radiology testing increased the diagnostic yield, investigators said, with a sensitivity of 79.2% and specificity of 90.6%.

“This might suggest that the implementation of this into a local [multidisciplinary discussion] with your local radiology expertise might really improve your recognition of UIP,” Dr. Dilling said.

Dr. Dilling reported disclosures related to Bellerophon, Boehringer Ingelheim, Genentech, Nitto Denko, and Lung Bioengineering.

Although genomic testing is useful when an interstitial lung disease diagnosis is uncertain, the testing results themselves aren’t sufficient to make the diagnosis, Daniel Dilling, MD, FCCP, said in a presentation at the annual meeting of the American College of Chest Physicians, which was held virtually.

The genomic classifier (Envisia, Veracyte) helps differentiate idiopathic pulmonary fibrosis (IPF) by detecting usual interstitial pneumonia (UIP), the hallmark pattern of this interstitial lung disease.

However, UIP is just one piece of the larger diagnostic puzzle, according to Dr. Dilling, professor of medicine in the interstitial lung disease program at Loyola University Medical Center in Maywood, Ill.

“Remember, it’s just a pattern, and not a diagnosis of IPF,” Dr. Dilling said in his presentation.

Genomic classifier results correlate well with both histologic and radiographic UIP pattern, studies show.

However, Dr. Dilling said the value of the genomic classifier is not in isolation.

“We don’t use this in a vacuum,” he said. “It increases our confidence and consensus, but it has to be incorporated into a multidisciplinary discussion group.”
 

Part of the diagnostic pathway

Dr. Dilling said the genomic classifier should be considered part of a diagnostic pathway in uncertain cases, particularly when the risk of surgical lung biopsy is high.

Current clinical practice guidelines recommend surgical lung biopsy for histopathologic diagnosis when clinical and radiologic findings are not definitive for IPF, the speaker said.

However, surgical lung biopsy carries some risk, and sometimes it can’t be done, he added.

In his presentation, Dr. Dilling cited a systematic review and meta-analysis of 23 studies looking at surgical lung biopsy for the diagnosis of interstitial lung diseases.

The postoperative mortality rate was 3.6% in that meta-analysis, published in 2015 in the Journal of Thoracic and Cardiovascular Surgery.

“The final decision regarding whether or not to perform a [surgical lung biopsy] must be based on the balance between benefits to establish a secure diagnosis and the potential risks,” authors wrote at the time.

Mortality risk is higher in immunocompromised and acutely ill patient populations, according to Dr. Dilling, who added that as many of 19% of patients will have complications from surgical lung biopsy.
 

Genomic classifier studies

In a proof-of-principle study, published in 2017 in the Annals of the American Thoracic Society, authors described how they used machine learning to train an algorithm to distinguish UIP from non-UIP pattern in tissue obtained by transbronchial biopsy (TBB).

The top-performing algorithm distinguished UIP from non-UIP conditions in single TBB samples with specificity of 86% and sensitivity of 63%, according to investigators, who said at the time that independent validation would be needed before the genomic classifier could be applied in clinical settings.

In a prospective validation study, published in 2019 in The Lancet Respiratory Medicine, the genomic classifier identified UIP in TBB samples from 49 patients with a specificity of 88% and sensitivity of 70%.

Excluding patients with definite or probable UIP as shown on high-resolution computed tomography, results show that the classifier had a sensitivity of 76%, specificity of 88%, and positive predictive value of 81%.

“The performance of the test is good, even in that scenario,” Dr. Dilling said.
 

Real-world results

Dr. Dilling also highlighted a “real-world” study, published earlier in 2021, demonstrating that UIP pattern recognized by a genomic classifier had encouraging sensitivity and specificity when combined with high-resolution CT and clinical factors.

That study included 96 patients who had both diagnostic lung pathology and a transbronchial lung biopsy for molecular testing with the classifier.

The classifier had a sensitivity of 60.3% and a specificity of 92.1% for histology-proven UIP pattern, investigators said in their report, which appears in the American Journal of Respiratory and Critical Care Medicine.

Local radiologists identified UIP with a sensitivity of 34.0% and specificity of 96.9%. But adding genomic classifier testing to local radiology testing increased the diagnostic yield, investigators said, with a sensitivity of 79.2% and specificity of 90.6%.

“This might suggest that the implementation of this into a local [multidisciplinary discussion] with your local radiology expertise might really improve your recognition of UIP,” Dr. Dilling said.

Dr. Dilling reported disclosures related to Bellerophon, Boehringer Ingelheim, Genentech, Nitto Denko, and Lung Bioengineering.

Initiating treatment of polyarticular juvenile idiopathic arthritis (polyJIA) with both a conventional synthetic disease-modifying antirheumatic drug and a biologic DMARD resulted in more patients achieving clinical inactive disease 2 years later than did starting with only a csDMARD and stepping up to a biologic, according to data presented at the virtual annual meeting of the American College of Rheumatology.

“The 24-month results support the 12-month primary results that suggested that the early-combination group was superior and that, at 24 months, more early combination CTP [consensus treatment plan] patients achieve CID [clinical inactive disease], compared to step up,” Yukiko Kimura, MD, division chief of pediatric rheumatology at HMH Hackensack (N.J.) University Medical Center, told attendees. “This suggests that starting biologics early in polyJIA may lead to better long-term outcomes in many patients.”

Dr. Kimura noted that polyarticular JIA patients are already at risk for poor outcomes, and initial therapy can especially impact outcomes. Further, little evidence exists to suggest when the best time is to start biologics, a gap this study aimed to address.

Diane Brown, MD, PhD, a pediatric rheumatologist at Children’s Hospital Los Angeles who was not involved in the study, was pleased to see the results, which she said support her own preferences and practice patterns.

“Starting sooner with combination therapy, taking advantage of the advances with biologics and our long history with methotrexate at the same time, gives better outcomes for the long run,” Dr. Brown said in an interview. “Having studies like this to back up my own recommendations can be very powerful when talking to families, and it is absolutely invaluable when battling with insurance companies who always want you to take the cheapest road.”
 

Study details

The findings were an update of 12-month results in the CARRA STOP-JIA study that enrolled 400 untreated patients with polyJIA and compared three Childhood Arthritis and Rheumatology Research Alliance (CARRA) CTPs. Overall, 49.5% of participants received biologics within 3 months of starting the study. For these updated results, 275 participants had complete data at 24 months for the three CTPs:

• A step-up group of 177 patients who started therapy with a csDMARD and added a biologic if needed at least 3 months later
• An early-combination group of 73 patients who started therapy with a csDMARD and biologic together
• A biologic-first group of 25 patients who started with biologic monotherapy, adding a csDMARD only if needed at least 3 months later.

The primary outcome was the percentage of participants who reached CID without taking glucocorticoids at 24 months. Since the participants were not randomized, the researchers made adjustments to account for baseline differences between the groups, including differences in JIA categories, number of active joints, physician global assessment of disease activity, and the clinical Juvenile Arthritis Disease Activity Score based on 10 joints (cJADAS10).

At 24 months in an intention to treat analysis, 59.4% of the early-combination group had achieved CID, compared with 48% of the biologic-first group and 40.1% of the step-up group (P = .009 for early combination vs. step up). All three groups had improved since the 12-month time point, when 37% of the early-combination group, 24% of the biologic-first group, and 32% of the step-up group had reached CID.

There were no significant differences between the groups in secondary outcomes of achieving cJADAS10 inactive disease of 2.5 or less or 70% improvement in pediatric ACR response criteria at 24 months. All groups improved in PROMIS pain interference or mobility measures from baseline. Most of the 17 severe adverse events were infections.
 

Moving from step-up therapy to early-combination treatment

Dr. Brown said that she spent many years in her practice using the step-up therapy because it was difficult to get insurance companies to pay for biologics without first showing that methotrexate was insufficient.

”But methotrexate takes so long to control the disease that you need a lot of steroids, with all of their side effects, at least temporarily, or you must simply accept a longer period of active and symptomatic disease before you get to that desired state of clinically inactive disease,” Dr. Brown said. “And during that time, you can be accumulating what may be permanent damage to joints, as well as increase in risk of contractures and deconditioning for that child who is too uncomfortable to move and exercise and play normally.”

Dr. Brown is also wary of using a biologic as an initial therapy by itself because the actions of biologics are so specific. ”I like to back up the powerful, rapid, and specific actions of a biologic with the broader, if slower, action of methotrexate to minimize chances that the immune system is going to find a way around blockade of a single cytokine by your biologic,” she said.

While patient preference will also play a role in what CTP patients with polyJIA start with, Dr. Brown said that she believes more medication upfront can result in less medication and better outcomes in the long run, as the findings of this study suggest. The results here are helpful when speaking with families who are anxious about “so much medicine” or “such powerful medicines,” she said. ”I hope it will also help ease the fears of other providers who share the same concerns about ‘so much medicine.’ ”

The study’s biggest limitation is not being a randomized, controlled trial, but Dr. Brown said the researchers demonstrated effectively that the disease burden remains similar across the groups at baseline.

”It would also be useful to have a clear breakdown of adverse events and opportunistic infections because an excess of opportunistic infections would be a key concern with early combination therapy,” she said, although she added that the study overall was a ”beautiful example of the value of registry data.”

Dr. Kimura emphasized that polyJIA remains a challenging disease to treat, with 40%-60% of participants not reaching CID at 24 months. The registry follow-up will continue for up to 10 years to hopefully provide more information about longer-term outcomes from different treatments.

The research was funded by a grant from Genentech to CARRA. Dr. Kimura reported royalties from UpToDate and salary support from CARRA. Dr. Brown had no disclosures.

Initiating treatment of polyarticular juvenile idiopathic arthritis (polyJIA) with both a conventional synthetic disease-modifying antirheumatic drug and a biologic DMARD resulted in more patients achieving clinical inactive disease 2 years later than did starting with only a csDMARD and stepping up to a biologic, according to data presented at the virtual annual meeting of the American College of Rheumatology.

“The 24-month results support the 12-month primary results that suggested that the early-combination group was superior and that, at 24 months, more early combination CTP [consensus treatment plan] patients achieve CID [clinical inactive disease], compared to step up,” Yukiko Kimura, MD, division chief of pediatric rheumatology at HMH Hackensack (N.J.) University Medical Center, told attendees. “This suggests that starting biologics early in polyJIA may lead to better long-term outcomes in many patients.”

Dr. Kimura noted that polyarticular JIA patients are already at risk for poor outcomes, and initial therapy can especially impact outcomes. Further, little evidence exists to suggest when the best time is to start biologics, a gap this study aimed to address.

Diane Brown, MD, PhD, a pediatric rheumatologist at Children’s Hospital Los Angeles who was not involved in the study, was pleased to see the results, which she said support her own preferences and practice patterns.

“Starting sooner with combination therapy, taking advantage of the advances with biologics and our long history with methotrexate at the same time, gives better outcomes for the long run,” Dr. Brown said in an interview. “Having studies like this to back up my own recommendations can be very powerful when talking to families, and it is absolutely invaluable when battling with insurance companies who always want you to take the cheapest road.”
 

Study details

The findings were an update of 12-month results in the CARRA STOP-JIA study that enrolled 400 untreated patients with polyJIA and compared three Childhood Arthritis and Rheumatology Research Alliance (CARRA) CTPs. Overall, 49.5% of participants received biologics within 3 months of starting the study. For these updated results, 275 participants had complete data at 24 months for the three CTPs:

• A step-up group of 177 patients who started therapy with a csDMARD and added a biologic if needed at least 3 months later
• An early-combination group of 73 patients who started therapy with a csDMARD and biologic together
• A biologic-first group of 25 patients who started with biologic monotherapy, adding a csDMARD only if needed at least 3 months later.

The primary outcome was the percentage of participants who reached CID without taking glucocorticoids at 24 months. Since the participants were not randomized, the researchers made adjustments to account for baseline differences between the groups, including differences in JIA categories, number of active joints, physician global assessment of disease activity, and the clinical Juvenile Arthritis Disease Activity Score based on 10 joints (cJADAS10).

At 24 months in an intention to treat analysis, 59.4% of the early-combination group had achieved CID, compared with 48% of the biologic-first group and 40.1% of the step-up group (P = .009 for early combination vs. step up). All three groups had improved since the 12-month time point, when 37% of the early-combination group, 24% of the biologic-first group, and 32% of the step-up group had reached CID.

There were no significant differences between the groups in secondary outcomes of achieving cJADAS10 inactive disease of 2.5 or less or 70% improvement in pediatric ACR response criteria at 24 months. All groups improved in PROMIS pain interference or mobility measures from baseline. Most of the 17 severe adverse events were infections.
 

Moving from step-up therapy to early-combination treatment

Dr. Brown said that she spent many years in her practice using the step-up therapy because it was difficult to get insurance companies to pay for biologics without first showing that methotrexate was insufficient.

”But methotrexate takes so long to control the disease that you need a lot of steroids, with all of their side effects, at least temporarily, or you must simply accept a longer period of active and symptomatic disease before you get to that desired state of clinically inactive disease,” Dr. Brown said. “And during that time, you can be accumulating what may be permanent damage to joints, as well as increase in risk of contractures and deconditioning for that child who is too uncomfortable to move and exercise and play normally.”

Dr. Brown is also wary of using a biologic as an initial therapy by itself because the actions of biologics are so specific. ”I like to back up the powerful, rapid, and specific actions of a biologic with the broader, if slower, action of methotrexate to minimize chances that the immune system is going to find a way around blockade of a single cytokine by your biologic,” she said.

While patient preference will also play a role in what CTP patients with polyJIA start with, Dr. Brown said that she believes more medication upfront can result in less medication and better outcomes in the long run, as the findings of this study suggest. The results here are helpful when speaking with families who are anxious about “so much medicine” or “such powerful medicines,” she said. ”I hope it will also help ease the fears of other providers who share the same concerns about ‘so much medicine.’ ”

The study’s biggest limitation is not being a randomized, controlled trial, but Dr. Brown said the researchers demonstrated effectively that the disease burden remains similar across the groups at baseline.

”It would also be useful to have a clear breakdown of adverse events and opportunistic infections because an excess of opportunistic infections would be a key concern with early combination therapy,” she said, although she added that the study overall was a ”beautiful example of the value of registry data.”

Dr. Kimura emphasized that polyJIA remains a challenging disease to treat, with 40%-60% of participants not reaching CID at 24 months. The registry follow-up will continue for up to 10 years to hopefully provide more information about longer-term outcomes from different treatments.

The research was funded by a grant from Genentech to CARRA. Dr. Kimura reported royalties from UpToDate and salary support from CARRA. Dr. Brown had no disclosures.

Initiating treatment of polyarticular juvenile idiopathic arthritis (polyJIA) with both a conventional synthetic disease-modifying antirheumatic drug and a biologic DMARD resulted in more patients achieving clinical inactive disease 2 years later than did starting with only a csDMARD and stepping up to a biologic, according to data presented at the virtual annual meeting of the American College of Rheumatology.

“The 24-month results support the 12-month primary results that suggested that the early-combination group was superior and that, at 24 months, more early combination CTP [consensus treatment plan] patients achieve CID [clinical inactive disease], compared to step up,” Yukiko Kimura, MD, division chief of pediatric rheumatology at HMH Hackensack (N.J.) University Medical Center, told attendees. “This suggests that starting biologics early in polyJIA may lead to better long-term outcomes in many patients.”

Dr. Kimura noted that polyarticular JIA patients are already at risk for poor outcomes, and initial therapy can especially impact outcomes. Further, little evidence exists to suggest when the best time is to start biologics, a gap this study aimed to address.

Diane Brown, MD, PhD, a pediatric rheumatologist at Children’s Hospital Los Angeles who was not involved in the study, was pleased to see the results, which she said support her own preferences and practice patterns.

“Starting sooner with combination therapy, taking advantage of the advances with biologics and our long history with methotrexate at the same time, gives better outcomes for the long run,” Dr. Brown said in an interview. “Having studies like this to back up my own recommendations can be very powerful when talking to families, and it is absolutely invaluable when battling with insurance companies who always want you to take the cheapest road.”
 

Study details

The findings were an update of 12-month results in the CARRA STOP-JIA study that enrolled 400 untreated patients with polyJIA and compared three Childhood Arthritis and Rheumatology Research Alliance (CARRA) CTPs. Overall, 49.5% of participants received biologics within 3 months of starting the study. For these updated results, 275 participants had complete data at 24 months for the three CTPs:

• A step-up group of 177 patients who started therapy with a csDMARD and added a biologic if needed at least 3 months later
• An early-combination group of 73 patients who started therapy with a csDMARD and biologic together
• A biologic-first group of 25 patients who started with biologic monotherapy, adding a csDMARD only if needed at least 3 months later.

The primary outcome was the percentage of participants who reached CID without taking glucocorticoids at 24 months. Since the participants were not randomized, the researchers made adjustments to account for baseline differences between the groups, including differences in JIA categories, number of active joints, physician global assessment of disease activity, and the clinical Juvenile Arthritis Disease Activity Score based on 10 joints (cJADAS10).

At 24 months in an intention to treat analysis, 59.4% of the early-combination group had achieved CID, compared with 48% of the biologic-first group and 40.1% of the step-up group (P = .009 for early combination vs. step up). All three groups had improved since the 12-month time point, when 37% of the early-combination group, 24% of the biologic-first group, and 32% of the step-up group had reached CID.

There were no significant differences between the groups in secondary outcomes of achieving cJADAS10 inactive disease of 2.5 or less or 70% improvement in pediatric ACR response criteria at 24 months. All groups improved in PROMIS pain interference or mobility measures from baseline. Most of the 17 severe adverse events were infections.
 

Moving from step-up therapy to early-combination treatment

Dr. Brown said that she spent many years in her practice using the step-up therapy because it was difficult to get insurance companies to pay for biologics without first showing that methotrexate was insufficient.

”But methotrexate takes so long to control the disease that you need a lot of steroids, with all of their side effects, at least temporarily, or you must simply accept a longer period of active and symptomatic disease before you get to that desired state of clinically inactive disease,” Dr. Brown said. “And during that time, you can be accumulating what may be permanent damage to joints, as well as increase in risk of contractures and deconditioning for that child who is too uncomfortable to move and exercise and play normally.”

Dr. Brown is also wary of using a biologic as an initial therapy by itself because the actions of biologics are so specific. ”I like to back up the powerful, rapid, and specific actions of a biologic with the broader, if slower, action of methotrexate to minimize chances that the immune system is going to find a way around blockade of a single cytokine by your biologic,” she said.

While patient preference will also play a role in what CTP patients with polyJIA start with, Dr. Brown said that she believes more medication upfront can result in less medication and better outcomes in the long run, as the findings of this study suggest. The results here are helpful when speaking with families who are anxious about “so much medicine” or “such powerful medicines,” she said. ”I hope it will also help ease the fears of other providers who share the same concerns about ‘so much medicine.’ ”

The study’s biggest limitation is not being a randomized, controlled trial, but Dr. Brown said the researchers demonstrated effectively that the disease burden remains similar across the groups at baseline.

”It would also be useful to have a clear breakdown of adverse events and opportunistic infections because an excess of opportunistic infections would be a key concern with early combination therapy,” she said, although she added that the study overall was a ”beautiful example of the value of registry data.”

Dr. Kimura emphasized that polyJIA remains a challenging disease to treat, with 40%-60% of participants not reaching CID at 24 months. The registry follow-up will continue for up to 10 years to hopefully provide more information about longer-term outcomes from different treatments.

The research was funded by a grant from Genentech to CARRA. Dr. Kimura reported royalties from UpToDate and salary support from CARRA. Dr. Brown had no disclosures.

LAS VEGAS – Risankizumab (Skyrizi, AbbVie) provides early and lasting benefits for patients with Crohn’s disease, phase 3 trials indicate.

Based on these and other recent findings, the drug could be used as a first-line treatment and even displace ustekinumab (Stelara, Janssen), which itself was approved by the Food and Drug Administration for Crohn’s disease in 2016, according to David Rubin, MD, the Joseph B. Kirsner Professor of Medicine at the University of Chicago.

“The drug works fast,” Dr. Rubin said in an interview. “If you start this therapy in patients with moderate to severe Crohn’s disease, they’re likely to feel better within the first few weeks.”

Dr. Rubin presented the findings on the drug’s early onset at the annual meeting of the American College of Gastroenterology. A related trial presented at the meeting showed the drug continuing to perform well up to 52 weeks.

Advances in immunomodulation have allowed drug companies to feed multiple new therapies into the pipeline for Crohn’s disease and related conditions in recent years, giving hope to the many patients who have not been able to benefit from older classes of drugs, such as biologics.

A humanized immunoglobulin G1 (IgG1) monoclonal antibody, risankizumab blocks interleukin (IL) 23 by binding to its p19 subunit. IL-23 is a cytokine implicated in several chronic immune disorders, including Crohn’s disease and psoriasis. Researchers hope that risankizumab will prove more selective, with a better safety profile, than previous drugs in its class. The FDA approved risankizumab in April 2019 for the treatment of moderate to severe plaque psoriasis.
 

MOTIVATE and ADVANCE studies

The two induction trials for Crohn’s disease enrolled slightly different populations.

The MOTIVATE study enrolled patients who had responded inadequately or were intolerant to biologic therapy. In this trial, the investigators assigned 205 patients to 1,200 mg of risankizumab, 206 patients to 600 mg of risankizumab, and 207 patients to placebo.

The ADVANCE study enrolled patients who had responded inadequately or could not tolerate either biologic or conventional therapy. In this trial, investigators randomly assigned 372 patients to 1,200 mg of risankizumab, 373 patients to 600 mg of risankizumab, and 186 patients to placebo.

In both trials, intravenous injections were given at weeks 0, 4, and 8.

The researchers defined a Crohn’s Disease Activity Index (CDAI) clinical remission as a score less than 150. They defined a Stool Frequency and Abdominal Pain Score (SF/APS) clinical remission as a soft stool frequency of no more than 2.8, and an abdominal pain score of no more than 1 and not worse than baseline.

A CDAI clinical response was at least a 100-point decrease from baseline. The SF/APS enhanced clinical response was at least a 60% decrease in average daily stool frequency or at least a 35% decrease in average daily abdominal pain, with both not worse than baseline.

At 4 weeks, the researchers found that the percentage of patients who achieved CDAI clinical remission in both risankizumab groups of both studies was greater than in the placebo group. The difference was statistically significant (P ≤ .01 in ADVANCE and P ≤ .05 in MOTIVATE), and it continued to grow at 8 weeks and 12 weeks.

By 12 weeks in the ADVANCE trial, according to a press release from AbbVie, 45% of patients on the 600-mg dose of risankizumab and 42% on the 1,200-mg dose of risankizumab had achieved CDAI clinical remission, compared with 25% of those on placebo, which was statistically significant (P < .001). For the MOTIVATE trial, the results were significantly better for patients in the risankizumab groups than for those in the placebo group.

In both trials, the treated groups continued to improve faster than the placebo groups through 12 weeks. Improvements in SF/APS enhanced clinical response largely paralleled those for CDAI clinical remission.

“It did show very good results,” session moderator Jonathan Leighton, MD, professor of medicine and chair of the division of gastroenterology at Mayo Clinic in Phoenix, Ariz., said in an interview with Medscape Medical News. “But basically, it’s so early that we don’t have all the data.” In particular, he would have liked to see whether patients responded to the drug before week 4.
 

FORTIFY study

In FORTIFY, the maintenance trial that followed, the researchers rerandomized those patients who had responded to risankizumab into three groups. Two groups received subcutaneous injections of risankizumab, with 179 patients getting 360 mg and another 179 patients getting 180 mg. The placebo group included the remaining 184 patients.

At week 52, 40.9% of patients in the placebo group were in clinical remission, compared with 52.2% in the 360-mg group and 55.4% in the 180-mg group, which was statistically significant (P = .005 for 360 mg, and P = .003 for 180 mg.)

“It showed us that [risankizumab] could achieve deep remission, which means patients achieving remission endoscopically in combination with clinical remission,” the presenter, Marla Dubinsky, MD, professor of pediatrics and medicine in the division of pediatric gastroenterology at Icahn School of Medicine at Mount Sinai in New York, said in an interview.

Over the 52 weeks, deep remission and endoscopic remission rates increased in the 360-mg group, held steady in the 180-mg group, and decreased in the placebo group. Mean fecal calprotectin and C-reactive protein levels decreased in the risankizumab groups and increased in the placebo group.

There were more total treatment-emergent adverse events per 100 patient-years in the placebo group (339.7) than in the 360-mg group (269.3) or the 180-mg group (283.5). The same difference between groups was true of severe treatment-emergent adverse events. Serious events and events leading to discontinuation were similar in the three groups.

Dr. Leighton reports financial relationships to Olympus and Pfizer. Dr. Rubin reports financial relationships to AbbVie, AltruBio, Allergan, Arena Pharmaceuticals, Athos Therapeutics, Bellatrix, Boehringer Ingelheim, Bristol Myers Squibb, Celgene/Syneos, Connect Biopharma, GalenPharma/Atlantica, Genentech/Roche, Gilead, InDex Pharmaceuticals, Ironwood, Iterative Scopes, Janssen, Lilly, Materia Prima Farmaceutica, Pfizer, Prometheus Biosciences, Reistone, Takeda, and TECHLAB. Dr. Dubinsky reports financial relationships to all or most of the companies making drugs for inflammatory bowel disease. The studies were funded by AbbVie.

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

LAS VEGAS – Risankizumab (Skyrizi, AbbVie) provides early and lasting benefits for patients with Crohn’s disease, phase 3 trials indicate.

Based on these and other recent findings, the drug could be used as a first-line treatment and even displace ustekinumab (Stelara, Janssen), which itself was approved by the Food and Drug Administration for Crohn’s disease in 2016, according to David Rubin, MD, the Joseph B. Kirsner Professor of Medicine at the University of Chicago.

“The drug works fast,” Dr. Rubin said in an interview. “If you start this therapy in patients with moderate to severe Crohn’s disease, they’re likely to feel better within the first few weeks.”

Dr. Rubin presented the findings on the drug’s early onset at the annual meeting of the American College of Gastroenterology. A related trial presented at the meeting showed the drug continuing to perform well up to 52 weeks.

Advances in immunomodulation have allowed drug companies to feed multiple new therapies into the pipeline for Crohn’s disease and related conditions in recent years, giving hope to the many patients who have not been able to benefit from older classes of drugs, such as biologics.

A humanized immunoglobulin G1 (IgG1) monoclonal antibody, risankizumab blocks interleukin (IL) 23 by binding to its p19 subunit. IL-23 is a cytokine implicated in several chronic immune disorders, including Crohn’s disease and psoriasis. Researchers hope that risankizumab will prove more selective, with a better safety profile, than previous drugs in its class. The FDA approved risankizumab in April 2019 for the treatment of moderate to severe plaque psoriasis.
 

MOTIVATE and ADVANCE studies

The two induction trials for Crohn’s disease enrolled slightly different populations.

The MOTIVATE study enrolled patients who had responded inadequately or were intolerant to biologic therapy. In this trial, the investigators assigned 205 patients to 1,200 mg of risankizumab, 206 patients to 600 mg of risankizumab, and 207 patients to placebo.

The ADVANCE study enrolled patients who had responded inadequately or could not tolerate either biologic or conventional therapy. In this trial, investigators randomly assigned 372 patients to 1,200 mg of risankizumab, 373 patients to 600 mg of risankizumab, and 186 patients to placebo.

In both trials, intravenous injections were given at weeks 0, 4, and 8.

The researchers defined a Crohn’s Disease Activity Index (CDAI) clinical remission as a score less than 150. They defined a Stool Frequency and Abdominal Pain Score (SF/APS) clinical remission as a soft stool frequency of no more than 2.8, and an abdominal pain score of no more than 1 and not worse than baseline.

A CDAI clinical response was at least a 100-point decrease from baseline. The SF/APS enhanced clinical response was at least a 60% decrease in average daily stool frequency or at least a 35% decrease in average daily abdominal pain, with both not worse than baseline.

At 4 weeks, the researchers found that the percentage of patients who achieved CDAI clinical remission in both risankizumab groups of both studies was greater than in the placebo group. The difference was statistically significant (P ≤ .01 in ADVANCE and P ≤ .05 in MOTIVATE), and it continued to grow at 8 weeks and 12 weeks.

By 12 weeks in the ADVANCE trial, according to a press release from AbbVie, 45% of patients on the 600-mg dose of risankizumab and 42% on the 1,200-mg dose of risankizumab had achieved CDAI clinical remission, compared with 25% of those on placebo, which was statistically significant (P < .001). For the MOTIVATE trial, the results were significantly better for patients in the risankizumab groups than for those in the placebo group.

In both trials, the treated groups continued to improve faster than the placebo groups through 12 weeks. Improvements in SF/APS enhanced clinical response largely paralleled those for CDAI clinical remission.

“It did show very good results,” session moderator Jonathan Leighton, MD, professor of medicine and chair of the division of gastroenterology at Mayo Clinic in Phoenix, Ariz., said in an interview with Medscape Medical News. “But basically, it’s so early that we don’t have all the data.” In particular, he would have liked to see whether patients responded to the drug before week 4.
 

FORTIFY study

In FORTIFY, the maintenance trial that followed, the researchers rerandomized those patients who had responded to risankizumab into three groups. Two groups received subcutaneous injections of risankizumab, with 179 patients getting 360 mg and another 179 patients getting 180 mg. The placebo group included the remaining 184 patients.

At week 52, 40.9% of patients in the placebo group were in clinical remission, compared with 52.2% in the 360-mg group and 55.4% in the 180-mg group, which was statistically significant (P = .005 for 360 mg, and P = .003 for 180 mg.)

“It showed us that [risankizumab] could achieve deep remission, which means patients achieving remission endoscopically in combination with clinical remission,” the presenter, Marla Dubinsky, MD, professor of pediatrics and medicine in the division of pediatric gastroenterology at Icahn School of Medicine at Mount Sinai in New York, said in an interview.

Over the 52 weeks, deep remission and endoscopic remission rates increased in the 360-mg group, held steady in the 180-mg group, and decreased in the placebo group. Mean fecal calprotectin and C-reactive protein levels decreased in the risankizumab groups and increased in the placebo group.

There were more total treatment-emergent adverse events per 100 patient-years in the placebo group (339.7) than in the 360-mg group (269.3) or the 180-mg group (283.5). The same difference between groups was true of severe treatment-emergent adverse events. Serious events and events leading to discontinuation were similar in the three groups.

Dr. Leighton reports financial relationships to Olympus and Pfizer. Dr. Rubin reports financial relationships to AbbVie, AltruBio, Allergan, Arena Pharmaceuticals, Athos Therapeutics, Bellatrix, Boehringer Ingelheim, Bristol Myers Squibb, Celgene/Syneos, Connect Biopharma, GalenPharma/Atlantica, Genentech/Roche, Gilead, InDex Pharmaceuticals, Ironwood, Iterative Scopes, Janssen, Lilly, Materia Prima Farmaceutica, Pfizer, Prometheus Biosciences, Reistone, Takeda, and TECHLAB. Dr. Dubinsky reports financial relationships to all or most of the companies making drugs for inflammatory bowel disease. The studies were funded by AbbVie.

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

LAS VEGAS – Risankizumab (Skyrizi, AbbVie) provides early and lasting benefits for patients with Crohn’s disease, phase 3 trials indicate.

Based on these and other recent findings, the drug could be used as a first-line treatment and even displace ustekinumab (Stelara, Janssen), which itself was approved by the Food and Drug Administration for Crohn’s disease in 2016, according to David Rubin, MD, the Joseph B. Kirsner Professor of Medicine at the University of Chicago.

“The drug works fast,” Dr. Rubin said in an interview. “If you start this therapy in patients with moderate to severe Crohn’s disease, they’re likely to feel better within the first few weeks.”

Dr. Rubin presented the findings on the drug’s early onset at the annual meeting of the American College of Gastroenterology. A related trial presented at the meeting showed the drug continuing to perform well up to 52 weeks.

Advances in immunomodulation have allowed drug companies to feed multiple new therapies into the pipeline for Crohn’s disease and related conditions in recent years, giving hope to the many patients who have not been able to benefit from older classes of drugs, such as biologics.

A humanized immunoglobulin G1 (IgG1) monoclonal antibody, risankizumab blocks interleukin (IL) 23 by binding to its p19 subunit. IL-23 is a cytokine implicated in several chronic immune disorders, including Crohn’s disease and psoriasis. Researchers hope that risankizumab will prove more selective, with a better safety profile, than previous drugs in its class. The FDA approved risankizumab in April 2019 for the treatment of moderate to severe plaque psoriasis.
 

MOTIVATE and ADVANCE studies

The two induction trials for Crohn’s disease enrolled slightly different populations.

The MOTIVATE study enrolled patients who had responded inadequately or were intolerant to biologic therapy. In this trial, the investigators assigned 205 patients to 1,200 mg of risankizumab, 206 patients to 600 mg of risankizumab, and 207 patients to placebo.

The ADVANCE study enrolled patients who had responded inadequately or could not tolerate either biologic or conventional therapy. In this trial, investigators randomly assigned 372 patients to 1,200 mg of risankizumab, 373 patients to 600 mg of risankizumab, and 186 patients to placebo.

In both trials, intravenous injections were given at weeks 0, 4, and 8.

The researchers defined a Crohn’s Disease Activity Index (CDAI) clinical remission as a score less than 150. They defined a Stool Frequency and Abdominal Pain Score (SF/APS) clinical remission as a soft stool frequency of no more than 2.8, and an abdominal pain score of no more than 1 and not worse than baseline.

A CDAI clinical response was at least a 100-point decrease from baseline. The SF/APS enhanced clinical response was at least a 60% decrease in average daily stool frequency or at least a 35% decrease in average daily abdominal pain, with both not worse than baseline.

At 4 weeks, the researchers found that the percentage of patients who achieved CDAI clinical remission in both risankizumab groups of both studies was greater than in the placebo group. The difference was statistically significant (P ≤ .01 in ADVANCE and P ≤ .05 in MOTIVATE), and it continued to grow at 8 weeks and 12 weeks.

By 12 weeks in the ADVANCE trial, according to a press release from AbbVie, 45% of patients on the 600-mg dose of risankizumab and 42% on the 1,200-mg dose of risankizumab had achieved CDAI clinical remission, compared with 25% of those on placebo, which was statistically significant (P < .001). For the MOTIVATE trial, the results were significantly better for patients in the risankizumab groups than for those in the placebo group.

In both trials, the treated groups continued to improve faster than the placebo groups through 12 weeks. Improvements in SF/APS enhanced clinical response largely paralleled those for CDAI clinical remission.

“It did show very good results,” session moderator Jonathan Leighton, MD, professor of medicine and chair of the division of gastroenterology at Mayo Clinic in Phoenix, Ariz., said in an interview with Medscape Medical News. “But basically, it’s so early that we don’t have all the data.” In particular, he would have liked to see whether patients responded to the drug before week 4.
 

FORTIFY study

In FORTIFY, the maintenance trial that followed, the researchers rerandomized those patients who had responded to risankizumab into three groups. Two groups received subcutaneous injections of risankizumab, with 179 patients getting 360 mg and another 179 patients getting 180 mg. The placebo group included the remaining 184 patients.

At week 52, 40.9% of patients in the placebo group were in clinical remission, compared with 52.2% in the 360-mg group and 55.4% in the 180-mg group, which was statistically significant (P = .005 for 360 mg, and P = .003 for 180 mg.)

“It showed us that [risankizumab] could achieve deep remission, which means patients achieving remission endoscopically in combination with clinical remission,” the presenter, Marla Dubinsky, MD, professor of pediatrics and medicine in the division of pediatric gastroenterology at Icahn School of Medicine at Mount Sinai in New York, said in an interview.

Over the 52 weeks, deep remission and endoscopic remission rates increased in the 360-mg group, held steady in the 180-mg group, and decreased in the placebo group. Mean fecal calprotectin and C-reactive protein levels decreased in the risankizumab groups and increased in the placebo group.

There were more total treatment-emergent adverse events per 100 patient-years in the placebo group (339.7) than in the 360-mg group (269.3) or the 180-mg group (283.5). The same difference between groups was true of severe treatment-emergent adverse events. Serious events and events leading to discontinuation were similar in the three groups.

Dr. Leighton reports financial relationships to Olympus and Pfizer. Dr. Rubin reports financial relationships to AbbVie, AltruBio, Allergan, Arena Pharmaceuticals, Athos Therapeutics, Bellatrix, Boehringer Ingelheim, Bristol Myers Squibb, Celgene/Syneos, Connect Biopharma, GalenPharma/Atlantica, Genentech/Roche, Gilead, InDex Pharmaceuticals, Ironwood, Iterative Scopes, Janssen, Lilly, Materia Prima Farmaceutica, Pfizer, Prometheus Biosciences, Reistone, Takeda, and TECHLAB. Dr. Dubinsky reports financial relationships to all or most of the companies making drugs for inflammatory bowel disease. The studies were funded by AbbVie.

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

The rate of major adverse cardiac events (MACE) over 5 years is similar whether revascularization is guided by instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR), according to long-term results of the iFR-SWEDEHEART study.

“The results are about the same as reported at 12 months. There were no significant differences in any outcome we evaluated,” according to Matthias Götberg, MD, PhD.

When the initial results of the noninferiority iFR-SWEDEHEART trial were published after 1 year of follow-up, the primary MACE endpoint of death from any-cause nonfatal myocardial infarction, or unplanned revascularization, was met by 6.7% and 6.1% of those randomized to iFR or FFR, respectively.

These outcomes were not significantly different and placed iFR well within the predefined boundaries of noninferiority (P = .007).

In this new and final follow-up of iFR-SWEDEHEART, which evaluated the same 2,019 patients who were alive at 1 year (none were lost to follow-up), the MACE endpoint was met by 21.5% and 19.9% of those managed with iFR and FFR, respectively. The hazard ratio (1.09) had a wide 95% confidence interval (0.90-1.31) that did not approach statistical significance.
 

No differences seen across outcomes

When broken down into the MACE components, there were no differences between iFR and FFR, respectively, for all-cause death (9.4% vs. 7.9%), MI (5.8% vs. 5.7%) or unplanned revascularization (11.6% vs. 11.3%).

Across predefined subgroups, such as those defined by age, gender, stable versus unstable angina, and presence of risk factors such as diabetes, hypertension, hyperlipidemia, and smoking, there were also no significant differences in outcome.

At the time iFR-SWEDEHART was initiated, FFR had already been accepted as more effective than angiographic assessment to identify lesion ischemia and the need for percutaneous intervention (PCI). The iFR-SWEDEHEART trial tested iFR, a relatively new technology at the time, as a noninferior alternative. Unlike FFR, which requires adenosine to dilate the vessel, adding cost and patient discomfort, iFR measures the resting pressure gradient across the coronary lesion, and it is generally easier to perform.

“The advantage of iFR is that it provides an instantaneous lesion assessment without the need for adenosine,” Dr. Götberg explained in presenting the results at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.

When the procedural results were compared in the published study at 1 year, it was noted that the mean number of lesions evaluated per patient was higher (1.55 vs. 1.43; P = .002), but the proportion of lesions found functionally significant was lower (29.2% vs. 36.8%; P < .0001) among those randomized to iFR than in the FFR group.

While most other procedural characteristics, such as PCI access route, fluoroscopy time, and contrast use did not differ significantly, fewer stents were placed in patients managed with iFR (1.58 vs. 1.73; P = .048), and a reduction in the average procedural time of a few minutes approached significance (P = .09).
 

Patient discomfort is greater with FFR

Patient discomfort measured during the procedure did differ, according to Dr. Götberg, an interventional cardiologist at Skåne University Hospital, Lund, Sweden.

Only about 30% in the FFR group reported no discomfort. Most of the others reported mild or moderate discomfort, but nearly 10% characterized the discomfort as severe. In the iFR group, more than 95% reported no discomfort. All of the remaining patients reported discomfort level as mild.

Because differences in MACE would be most likely to occur in the first year after revascularization, the similarity of the 1- and 5-year results were expected, according to Dr. Götberg. However, a 5-year follow-up was considered prudent given the relatively limited experience with iFR when the study was designed. This technique is now well established and widely used.

The study supports the premise that quicker and easier-to-obtain results with iFR are obtained without sacrificing greater relative risk of failing to identify a vulnerable lesion, according to Dr. Götberg.

Nevertheless, iFR and FFR “are not an exact match,” according to Jennifer A. Rymer, MD, an interventional cardiologist and assistant professor of medicine at Duke University, Durham, N.C. Although she called this trial an “excellent” demonstration of comparable utility in distinguishing lesions that do not require intervention from those that do, she implied that some clinicians might still prefer FFR for other reasons.

For example, FFR provides information about coronary flow reserve and microvascular resistance that are relevant to the underlying pathophysiology in a diseased vessel, according to Shmuel Banai, MD, head of interventional cardiology, Tel Aviv Medical Center. Recognizing that this information is not as readily generated by iFR, he is among those who plan to continue to use FFR despite these results.

However, for those who are now routinely performing iFR for the purposes of guiding revascularization, “these data are reassuring,” said David Kandzari, MD, director of interventional cardiology, Piedmont Hart Institute, Atlanta. The 5-year data essentially eliminate the likelihood that iFR relative to FFR increases the risk of missing functionally significant lesions for revascularization procedures.

Dr. Götberg reports financial relationships with Abbott, Boston Scientific, Medtronic, and Phillips Healthcare. Dr. Rymer reports no potential financial conflicts of interest. Dr. Banai has a financial relationship with Neovasc. Dr. Kandzari reports financial relationships with Ablative Solutions and Medtronic.

The rate of major adverse cardiac events (MACE) over 5 years is similar whether revascularization is guided by instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR), according to long-term results of the iFR-SWEDEHEART study.

“The results are about the same as reported at 12 months. There were no significant differences in any outcome we evaluated,” according to Matthias Götberg, MD, PhD.

When the initial results of the noninferiority iFR-SWEDEHEART trial were published after 1 year of follow-up, the primary MACE endpoint of death from any-cause nonfatal myocardial infarction, or unplanned revascularization, was met by 6.7% and 6.1% of those randomized to iFR or FFR, respectively.

These outcomes were not significantly different and placed iFR well within the predefined boundaries of noninferiority (P = .007).

In this new and final follow-up of iFR-SWEDEHEART, which evaluated the same 2,019 patients who were alive at 1 year (none were lost to follow-up), the MACE endpoint was met by 21.5% and 19.9% of those managed with iFR and FFR, respectively. The hazard ratio (1.09) had a wide 95% confidence interval (0.90-1.31) that did not approach statistical significance.
 

No differences seen across outcomes

When broken down into the MACE components, there were no differences between iFR and FFR, respectively, for all-cause death (9.4% vs. 7.9%), MI (5.8% vs. 5.7%) or unplanned revascularization (11.6% vs. 11.3%).

Across predefined subgroups, such as those defined by age, gender, stable versus unstable angina, and presence of risk factors such as diabetes, hypertension, hyperlipidemia, and smoking, there were also no significant differences in outcome.

At the time iFR-SWEDEHART was initiated, FFR had already been accepted as more effective than angiographic assessment to identify lesion ischemia and the need for percutaneous intervention (PCI). The iFR-SWEDEHEART trial tested iFR, a relatively new technology at the time, as a noninferior alternative. Unlike FFR, which requires adenosine to dilate the vessel, adding cost and patient discomfort, iFR measures the resting pressure gradient across the coronary lesion, and it is generally easier to perform.

“The advantage of iFR is that it provides an instantaneous lesion assessment without the need for adenosine,” Dr. Götberg explained in presenting the results at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.

When the procedural results were compared in the published study at 1 year, it was noted that the mean number of lesions evaluated per patient was higher (1.55 vs. 1.43; P = .002), but the proportion of lesions found functionally significant was lower (29.2% vs. 36.8%; P < .0001) among those randomized to iFR than in the FFR group.

While most other procedural characteristics, such as PCI access route, fluoroscopy time, and contrast use did not differ significantly, fewer stents were placed in patients managed with iFR (1.58 vs. 1.73; P = .048), and a reduction in the average procedural time of a few minutes approached significance (P = .09).
 

Patient discomfort is greater with FFR

Patient discomfort measured during the procedure did differ, according to Dr. Götberg, an interventional cardiologist at Skåne University Hospital, Lund, Sweden.

Only about 30% in the FFR group reported no discomfort. Most of the others reported mild or moderate discomfort, but nearly 10% characterized the discomfort as severe. In the iFR group, more than 95% reported no discomfort. All of the remaining patients reported discomfort level as mild.

Because differences in MACE would be most likely to occur in the first year after revascularization, the similarity of the 1- and 5-year results were expected, according to Dr. Götberg. However, a 5-year follow-up was considered prudent given the relatively limited experience with iFR when the study was designed. This technique is now well established and widely used.

The study supports the premise that quicker and easier-to-obtain results with iFR are obtained without sacrificing greater relative risk of failing to identify a vulnerable lesion, according to Dr. Götberg.

Nevertheless, iFR and FFR “are not an exact match,” according to Jennifer A. Rymer, MD, an interventional cardiologist and assistant professor of medicine at Duke University, Durham, N.C. Although she called this trial an “excellent” demonstration of comparable utility in distinguishing lesions that do not require intervention from those that do, she implied that some clinicians might still prefer FFR for other reasons.

For example, FFR provides information about coronary flow reserve and microvascular resistance that are relevant to the underlying pathophysiology in a diseased vessel, according to Shmuel Banai, MD, head of interventional cardiology, Tel Aviv Medical Center. Recognizing that this information is not as readily generated by iFR, he is among those who plan to continue to use FFR despite these results.

However, for those who are now routinely performing iFR for the purposes of guiding revascularization, “these data are reassuring,” said David Kandzari, MD, director of interventional cardiology, Piedmont Hart Institute, Atlanta. The 5-year data essentially eliminate the likelihood that iFR relative to FFR increases the risk of missing functionally significant lesions for revascularization procedures.

Dr. Götberg reports financial relationships with Abbott, Boston Scientific, Medtronic, and Phillips Healthcare. Dr. Rymer reports no potential financial conflicts of interest. Dr. Banai has a financial relationship with Neovasc. Dr. Kandzari reports financial relationships with Ablative Solutions and Medtronic.

The rate of major adverse cardiac events (MACE) over 5 years is similar whether revascularization is guided by instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR), according to long-term results of the iFR-SWEDEHEART study.

“The results are about the same as reported at 12 months. There were no significant differences in any outcome we evaluated,” according to Matthias Götberg, MD, PhD.

When the initial results of the noninferiority iFR-SWEDEHEART trial were published after 1 year of follow-up, the primary MACE endpoint of death from any-cause nonfatal myocardial infarction, or unplanned revascularization, was met by 6.7% and 6.1% of those randomized to iFR or FFR, respectively.

These outcomes were not significantly different and placed iFR well within the predefined boundaries of noninferiority (P = .007).

In this new and final follow-up of iFR-SWEDEHEART, which evaluated the same 2,019 patients who were alive at 1 year (none were lost to follow-up), the MACE endpoint was met by 21.5% and 19.9% of those managed with iFR and FFR, respectively. The hazard ratio (1.09) had a wide 95% confidence interval (0.90-1.31) that did not approach statistical significance.
 

No differences seen across outcomes

When broken down into the MACE components, there were no differences between iFR and FFR, respectively, for all-cause death (9.4% vs. 7.9%), MI (5.8% vs. 5.7%) or unplanned revascularization (11.6% vs. 11.3%).

Across predefined subgroups, such as those defined by age, gender, stable versus unstable angina, and presence of risk factors such as diabetes, hypertension, hyperlipidemia, and smoking, there were also no significant differences in outcome.

At the time iFR-SWEDEHART was initiated, FFR had already been accepted as more effective than angiographic assessment to identify lesion ischemia and the need for percutaneous intervention (PCI). The iFR-SWEDEHEART trial tested iFR, a relatively new technology at the time, as a noninferior alternative. Unlike FFR, which requires adenosine to dilate the vessel, adding cost and patient discomfort, iFR measures the resting pressure gradient across the coronary lesion, and it is generally easier to perform.

“The advantage of iFR is that it provides an instantaneous lesion assessment without the need for adenosine,” Dr. Götberg explained in presenting the results at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.

When the procedural results were compared in the published study at 1 year, it was noted that the mean number of lesions evaluated per patient was higher (1.55 vs. 1.43; P = .002), but the proportion of lesions found functionally significant was lower (29.2% vs. 36.8%; P < .0001) among those randomized to iFR than in the FFR group.

While most other procedural characteristics, such as PCI access route, fluoroscopy time, and contrast use did not differ significantly, fewer stents were placed in patients managed with iFR (1.58 vs. 1.73; P = .048), and a reduction in the average procedural time of a few minutes approached significance (P = .09).
 

Patient discomfort is greater with FFR

Patient discomfort measured during the procedure did differ, according to Dr. Götberg, an interventional cardiologist at Skåne University Hospital, Lund, Sweden.

Only about 30% in the FFR group reported no discomfort. Most of the others reported mild or moderate discomfort, but nearly 10% characterized the discomfort as severe. In the iFR group, more than 95% reported no discomfort. All of the remaining patients reported discomfort level as mild.

Because differences in MACE would be most likely to occur in the first year after revascularization, the similarity of the 1- and 5-year results were expected, according to Dr. Götberg. However, a 5-year follow-up was considered prudent given the relatively limited experience with iFR when the study was designed. This technique is now well established and widely used.

The study supports the premise that quicker and easier-to-obtain results with iFR are obtained without sacrificing greater relative risk of failing to identify a vulnerable lesion, according to Dr. Götberg.

Nevertheless, iFR and FFR “are not an exact match,” according to Jennifer A. Rymer, MD, an interventional cardiologist and assistant professor of medicine at Duke University, Durham, N.C. Although she called this trial an “excellent” demonstration of comparable utility in distinguishing lesions that do not require intervention from those that do, she implied that some clinicians might still prefer FFR for other reasons.

For example, FFR provides information about coronary flow reserve and microvascular resistance that are relevant to the underlying pathophysiology in a diseased vessel, according to Shmuel Banai, MD, head of interventional cardiology, Tel Aviv Medical Center. Recognizing that this information is not as readily generated by iFR, he is among those who plan to continue to use FFR despite these results.

However, for those who are now routinely performing iFR for the purposes of guiding revascularization, “these data are reassuring,” said David Kandzari, MD, director of interventional cardiology, Piedmont Hart Institute, Atlanta. The 5-year data essentially eliminate the likelihood that iFR relative to FFR increases the risk of missing functionally significant lesions for revascularization procedures.

Dr. Götberg reports financial relationships with Abbott, Boston Scientific, Medtronic, and Phillips Healthcare. Dr. Rymer reports no potential financial conflicts of interest. Dr. Banai has a financial relationship with Neovasc. Dr. Kandzari reports financial relationships with Ablative Solutions and Medtronic.

The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (Saxenda, Novo Nordisk) was safe and effective for treating weight regain after Roux-en-Y gastric bypass (RYGB), in a randomized controlled trial.

That is, 132 patients who had lost at least 25% of their initial weight after RYGB and then gained at least 10% back were randomized 2:1 to receive liraglutide plus frequent lifestyle advice from a registered dietitian or lifestyle advice alone.

After a year, 69%, 48%, and 24% of patients who had received liraglutide lost at least 5%, 10%, and 15% of their study entry weight, respectively. In contrast, only 5% of patients in the control group lost at least 5% of their weight and none lost at least 10% of their weight.

“Liraglutide 3.0 mg/day, with lifestyle modification, was significantly more effective than placebo in treating weight regain after RYGB without increased risk of serious adverse events,” Holly F. Lofton, MD, summarized this week in an oral session at ObesityWeek®, the annual meeting of The Obesity Society.

Dr. Lofton, a clinical associate professor of surgery and medicine, and director, weight management program, NYU, Langone Health, explained to this news organization that she initiated the study after attending a “packed” session about post bariatric surgery weight regain at a prior American Society of Metabolic and Bariatric Surgery conference.

“The lecturers recommended conservative measures (such as reiterating the diet recommendations, exercise, [and] counseling), and revisional surgeries,” she said in an email, but at the time “there was no literature that provided direction on which pharmacotherapies are best for this population.”

It was known that decreases in endogenous GLP-1 levels coincide with weight regain, and liraglutide (Saxenda) was the only GLP-1 agonist approved for chronic weight management at the time, so she devised the current study protocol.

The findings are especially helpful for patients who are not candidates for bariatric surgery revisions, she noted. Further research is needed to investigate the effect of newer GLP-1 agonists, such as semaglutide (Wegovy), on weight regain following different types of bariatric surgery.

Asked to comment, Wendy C. King, PhD, who was not involved with this research, said that more than two-thirds of patients treated with 3 mg/day subcutaneous liraglutide injections in the current study lost at least 5% of their initial weight a year later, and 20% of them attained a weight as low as, or lower than, their lowest weight after bariatric surgery (nadir weight).

“The fact that both groups received lifestyle counseling from registered dietitians for just over a year, but only patients in the liraglutide group lost weight, on average, speaks to the difficulty of losing weight following weight regain post–bariatric surgery,” added Dr. King, an associate professor of epidemiology at the University of Pittsburgh, Pennsylvania.

This study “provides data that may help clinicians and patients understand the potential effect of adding liraglutide 3.0 mg/day to their weight loss efforts,” she told this news organization in an email.

However, “given that 42% of those on liraglutide reported gastrointestinal-related side effects, patients should also be counseled on this potential outcome and given suggestions for how to minimize such side effects,” Dr. King suggested.
 

Weight regain common, repeat surgery entails risk

Weight regain is common even years after bariatric surgery. Repeat surgery entails some risk, and lifestyle approaches alone are rarely successful in reversing weight regain, Dr. Lofton told the audience.

The researchers enrolled 132 adults who had a mean weight of 134 kg (295 pounds) when they underwent RYGB, and who lost at least 25% of their initial weight (mean weight loss of 38%) after the surgery, but who also regained at least 10% of their initial weight.

At enrollment of the current study (baseline), the patients had had RYGB 18 months to 10 years earlier (mean 5.7 years earlier) and now had a mean weight of 99 kg (218 pounds) and a mean BMI of 35.6 kg/m². None of the patients had diabetes.  

The patients were randomized to receive liraglutide (n = 89, 84% women) or placebo (n = 43, 88% women) for 56 weeks.

They were a mean age of 48 years, and about 59% were White and 25% were Black.

All patients had clinic visits every 3 months where they received lifestyle counseling from a registered dietitian.

At 12 months, patients in the liraglutide group had lost a mean of 8.8% of their baseline weight, whereas those in the placebo group had gained a mean of 1.48% of their baseline weight.

There were no significant between-group differences in cardiometabolic variables.

None of the patients in the control group attained a weight that was as low as their nadir weight after RYGB.

The rates of nausea (25%), constipation (16%), and abdominal pain (10%) in the liraglutide group were higher than in the placebo group (7%, 14%, and 5%, respectively) but similar to rates of gastrointestinal side effects in other trials of this agent.

Dr. Lofton has disclosed receiving consulting fees and being on a speaker bureau for Novo Nordisk and receiving research funds from Boehringer Ingelheim, Eli Lilly, and Novo Nordisk. Dr. King has reported no relevant financial relationships.

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

The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (Saxenda, Novo Nordisk) was safe and effective for treating weight regain after Roux-en-Y gastric bypass (RYGB), in a randomized controlled trial.

That is, 132 patients who had lost at least 25% of their initial weight after RYGB and then gained at least 10% back were randomized 2:1 to receive liraglutide plus frequent lifestyle advice from a registered dietitian or lifestyle advice alone.

After a year, 69%, 48%, and 24% of patients who had received liraglutide lost at least 5%, 10%, and 15% of their study entry weight, respectively. In contrast, only 5% of patients in the control group lost at least 5% of their weight and none lost at least 10% of their weight.

“Liraglutide 3.0 mg/day, with lifestyle modification, was significantly more effective than placebo in treating weight regain after RYGB without increased risk of serious adverse events,” Holly F. Lofton, MD, summarized this week in an oral session at ObesityWeek®, the annual meeting of The Obesity Society.

Dr. Lofton, a clinical associate professor of surgery and medicine, and director, weight management program, NYU, Langone Health, explained to this news organization that she initiated the study after attending a “packed” session about post bariatric surgery weight regain at a prior American Society of Metabolic and Bariatric Surgery conference.

“The lecturers recommended conservative measures (such as reiterating the diet recommendations, exercise, [and] counseling), and revisional surgeries,” she said in an email, but at the time “there was no literature that provided direction on which pharmacotherapies are best for this population.”

It was known that decreases in endogenous GLP-1 levels coincide with weight regain, and liraglutide (Saxenda) was the only GLP-1 agonist approved for chronic weight management at the time, so she devised the current study protocol.

The findings are especially helpful for patients who are not candidates for bariatric surgery revisions, she noted. Further research is needed to investigate the effect of newer GLP-1 agonists, such as semaglutide (Wegovy), on weight regain following different types of bariatric surgery.

Asked to comment, Wendy C. King, PhD, who was not involved with this research, said that more than two-thirds of patients treated with 3 mg/day subcutaneous liraglutide injections in the current study lost at least 5% of their initial weight a year later, and 20% of them attained a weight as low as, or lower than, their lowest weight after bariatric surgery (nadir weight).

“The fact that both groups received lifestyle counseling from registered dietitians for just over a year, but only patients in the liraglutide group lost weight, on average, speaks to the difficulty of losing weight following weight regain post–bariatric surgery,” added Dr. King, an associate professor of epidemiology at the University of Pittsburgh, Pennsylvania.

This study “provides data that may help clinicians and patients understand the potential effect of adding liraglutide 3.0 mg/day to their weight loss efforts,” she told this news organization in an email.

However, “given that 42% of those on liraglutide reported gastrointestinal-related side effects, patients should also be counseled on this potential outcome and given suggestions for how to minimize such side effects,” Dr. King suggested.
 

Weight regain common, repeat surgery entails risk

Weight regain is common even years after bariatric surgery. Repeat surgery entails some risk, and lifestyle approaches alone are rarely successful in reversing weight regain, Dr. Lofton told the audience.

The researchers enrolled 132 adults who had a mean weight of 134 kg (295 pounds) when they underwent RYGB, and who lost at least 25% of their initial weight (mean weight loss of 38%) after the surgery, but who also regained at least 10% of their initial weight.

At enrollment of the current study (baseline), the patients had had RYGB 18 months to 10 years earlier (mean 5.7 years earlier) and now had a mean weight of 99 kg (218 pounds) and a mean BMI of 35.6 kg/m². None of the patients had diabetes.  

The patients were randomized to receive liraglutide (n = 89, 84% women) or placebo (n = 43, 88% women) for 56 weeks.

They were a mean age of 48 years, and about 59% were White and 25% were Black.

All patients had clinic visits every 3 months where they received lifestyle counseling from a registered dietitian.

At 12 months, patients in the liraglutide group had lost a mean of 8.8% of their baseline weight, whereas those in the placebo group had gained a mean of 1.48% of their baseline weight.

There were no significant between-group differences in cardiometabolic variables.

None of the patients in the control group attained a weight that was as low as their nadir weight after RYGB.

The rates of nausea (25%), constipation (16%), and abdominal pain (10%) in the liraglutide group were higher than in the placebo group (7%, 14%, and 5%, respectively) but similar to rates of gastrointestinal side effects in other trials of this agent.

Dr. Lofton has disclosed receiving consulting fees and being on a speaker bureau for Novo Nordisk and receiving research funds from Boehringer Ingelheim, Eli Lilly, and Novo Nordisk. Dr. King has reported no relevant financial relationships.

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

The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (Saxenda, Novo Nordisk) was safe and effective for treating weight regain after Roux-en-Y gastric bypass (RYGB), in a randomized controlled trial.

That is, 132 patients who had lost at least 25% of their initial weight after RYGB and then gained at least 10% back were randomized 2:1 to receive liraglutide plus frequent lifestyle advice from a registered dietitian or lifestyle advice alone.

After a year, 69%, 48%, and 24% of patients who had received liraglutide lost at least 5%, 10%, and 15% of their study entry weight, respectively. In contrast, only 5% of patients in the control group lost at least 5% of their weight and none lost at least 10% of their weight.

“Liraglutide 3.0 mg/day, with lifestyle modification, was significantly more effective than placebo in treating weight regain after RYGB without increased risk of serious adverse events,” Holly F. Lofton, MD, summarized this week in an oral session at ObesityWeek®, the annual meeting of The Obesity Society.

Dr. Lofton, a clinical associate professor of surgery and medicine, and director, weight management program, NYU, Langone Health, explained to this news organization that she initiated the study after attending a “packed” session about post bariatric surgery weight regain at a prior American Society of Metabolic and Bariatric Surgery conference.

“The lecturers recommended conservative measures (such as reiterating the diet recommendations, exercise, [and] counseling), and revisional surgeries,” she said in an email, but at the time “there was no literature that provided direction on which pharmacotherapies are best for this population.”

It was known that decreases in endogenous GLP-1 levels coincide with weight regain, and liraglutide (Saxenda) was the only GLP-1 agonist approved for chronic weight management at the time, so she devised the current study protocol.

The findings are especially helpful for patients who are not candidates for bariatric surgery revisions, she noted. Further research is needed to investigate the effect of newer GLP-1 agonists, such as semaglutide (Wegovy), on weight regain following different types of bariatric surgery.

Asked to comment, Wendy C. King, PhD, who was not involved with this research, said that more than two-thirds of patients treated with 3 mg/day subcutaneous liraglutide injections in the current study lost at least 5% of their initial weight a year later, and 20% of them attained a weight as low as, or lower than, their lowest weight after bariatric surgery (nadir weight).

“The fact that both groups received lifestyle counseling from registered dietitians for just over a year, but only patients in the liraglutide group lost weight, on average, speaks to the difficulty of losing weight following weight regain post–bariatric surgery,” added Dr. King, an associate professor of epidemiology at the University of Pittsburgh, Pennsylvania.

This study “provides data that may help clinicians and patients understand the potential effect of adding liraglutide 3.0 mg/day to their weight loss efforts,” she told this news organization in an email.

However, “given that 42% of those on liraglutide reported gastrointestinal-related side effects, patients should also be counseled on this potential outcome and given suggestions for how to minimize such side effects,” Dr. King suggested.
 

Weight regain common, repeat surgery entails risk

Weight regain is common even years after bariatric surgery. Repeat surgery entails some risk, and lifestyle approaches alone are rarely successful in reversing weight regain, Dr. Lofton told the audience.

The researchers enrolled 132 adults who had a mean weight of 134 kg (295 pounds) when they underwent RYGB, and who lost at least 25% of their initial weight (mean weight loss of 38%) after the surgery, but who also regained at least 10% of their initial weight.

At enrollment of the current study (baseline), the patients had had RYGB 18 months to 10 years earlier (mean 5.7 years earlier) and now had a mean weight of 99 kg (218 pounds) and a mean BMI of 35.6 kg/m². None of the patients had diabetes.  

The patients were randomized to receive liraglutide (n = 89, 84% women) or placebo (n = 43, 88% women) for 56 weeks.

They were a mean age of 48 years, and about 59% were White and 25% were Black.

All patients had clinic visits every 3 months where they received lifestyle counseling from a registered dietitian.

At 12 months, patients in the liraglutide group had lost a mean of 8.8% of their baseline weight, whereas those in the placebo group had gained a mean of 1.48% of their baseline weight.

There were no significant between-group differences in cardiometabolic variables.

None of the patients in the control group attained a weight that was as low as their nadir weight after RYGB.

The rates of nausea (25%), constipation (16%), and abdominal pain (10%) in the liraglutide group were higher than in the placebo group (7%, 14%, and 5%, respectively) but similar to rates of gastrointestinal side effects in other trials of this agent.

Dr. Lofton has disclosed receiving consulting fees and being on a speaker bureau for Novo Nordisk and receiving research funds from Boehringer Ingelheim, Eli Lilly, and Novo Nordisk. Dr. King has reported no relevant financial relationships.

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

For psychiatrists embarking on a telemedicine consultation, it might be helpful to review a checklist of steps that will reduce the risk of problems when things go wrong, according to an overview of the dangers at the virtual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists, sponsored by Medscape Live.

Ideally, telepsychiatry will function much like an inpatient office visit, but the dynamics differ – as do the things that can go wrong, according to Sanjay Gupta, MD, chief medical officer, BryLin Behavioral Health System, Buffalo, N.Y. “Issues can arise suddenly. You need contingency planning.”

At the outset, psychiatrists should establish the location of the patient. This is necessary at every telemedicine encounter. With a remote device, a patient could be essentially anywhere on Earth. Patients might not even remember to mention that they are vacationing in Australia.

The location of the patient is important in the event of an unexpected crisis. This is not only relevant to an unstable patient at risk of dangerous behavior, such as actively attempting suicide, but to patients who have a seizure or some other emergency that inhibits communication. Dr. Gupta advised obtaining phone numbers for crisis services relevant to the location of the patient, and this requires confirming that the patient is where he or she was expected to be.

In addition, there should be a plan for technological failure. As everyone knows, these failures, such as dysfunction of a device, a poor connection, or an Internet outage, can happen at any time. Both the clinician and the patient can derive reassurance from at least one if not two or more plans to reconnect in the event of these failures.

The visit should also begin with questions that will establish the patient has a sense of adequate privacy. This is one of the most common obstacles to an effective telemedicine consultation. Dr. Gupta pointed out that phone or computer cameras do not typically permit the clinician to exclude the presence of another individual sitting even a few feet away from the patient. With spouses and children nearby, there might be a tenuous sense of privacy even if they are unlikely to overhear the telemedicine visit.

One strategy that can be used to assess the patient’s level of comfort is to ask for a description of the patient’s surroundings and any other people at the location. Dr. Gupta also said it is appropriate to establish ground rules about recording of the session, which has its own potential to inhibit the interaction.

Warning that some form of consent to a telemedicine visit is mandatory in most states, Dr. Gupta also cautioned that a formal identification check is appropriate for a first-time visit. The risk of an individual offering a false identification is likely to be low, but it can be eliminated entirely by a protocol that verifies consent and identify before the clinical work begins.

Because of the importance of engaging patients quickly, Dr. Gupta called the first few minutes of a telemedicine visit “crucial.” By initiating the visit with a warm and respectful tone, by relaying a competent and professional appearance, and by establishing an atmosphere that encourages communication, the initial minutes of the call can set a tone that facilitates an effective visit.

Simple and established telehealth etiquette strategies should be employed, according to Dr. Gupta. He suggested paying attention to such issues as lighting, background, and camera position. Descriptions of what constitutes adequate lighting and background are easily obtained on free how-to websites, but the goal is to provide patients with a nondistracting and clear view of the clinician.

During a telemedicine visit, the clinician’s focus should remain on the patient, according to Dr. Gupta. He advised against taking notes or documenting the visit on an electronic health record during the course of the visit. Rather, he advised positioning the camera in a way that the patient feels eye contact is being made.

“It can be helpful to periodically summarize what the patient has said to demonstrate that you are fully engaged,” Dr. Gupta suggested.

Telemedicine is very effective for many but not all patients. Some, such as those with active psychosis, are not suited to this approach, but others are simply uncomfortable with this form of communication. Dr. Gupta suggested that clinicians should be mindful of the advantages and the limitations of telepsychiatry.

Ultimately, Dr. Gupta believes that the substantial expansion of telepsychiatry that took place during the COVID-19 pandemic is likely to persist when the pandemic ends, even if many of the changes that permitted its expansion, such as a relaxation of HIPPA requirements, are withdrawn. However, parity reimbursement for visits offered by telemedicine relative to those that are face-to-face, which greatly facilitated the growth of telepsychiatry, is not guaranteed, so this remains an unanswered question.

“The question is what will happen to the billing codes when we see COVID-19 in the rearview mirror, and the answer is that no one knows,” he said.
 

Uncertainty about future use

Other experts in this field agreed. James (Jay) H. Shore, MD, MPH, director of telemedicine, Helen and Arthur E. Johnson Depression Center, University of Colorado at Denver, Aurora, has long been an advocate for the value of telepsychiatry for reaching patients with limited psychosocial services. The attention drawn to this practice by the COVID-19 pandemic has been welcome, but he does not know how it will affect the future.

“There is too much uncertainty in the system to make a good prediction of where this may end up,” he said.

It is not just reimbursement that is at risk, according to Peter Yellowlees, MBBS, MD, chief wellness officer at the University of California, Davis. Also a longtime advocate of telepsychiatry, particularly to reach the underserved, Dr. Yellowlees pointed out that the ability to prescribe controlled substances through telemedicine and the ability to consult with patients across state lines might also be in jeopardy if and when rules for telemedicine are revisited after the pandemic.

“Many organizations are lobbying to make the pandemic changes permanent because they greatly support telemedicine delivery,” Dr. Yellowlees said, but agreed about the uncertainty regarding what policy makers will do.

Jayasudha Gude, MD, who is completing her residency in psychiatry at Zucker Hillside Hospital, Northwell Health, New York, recently led a literature review evaluating the needs and viability of telepsychiatry during and after the COVID-19 era (Cureus. 2021 Aug;13:e16974). Based on the benefits she identified in her review, she said, “I would definitely want to advocate for the continued use of telepsychiatry after the pandemic is over.” She hopes that psychiatrists who now have experience in this area will join her.

“I am hopeful that a lot of mental health providers will also be advocating since they have experience, and many will want to continue its use,” she said. Medscape Live and this news organization are owned by the same parent company. Dr. Gupta, Dr. Shore, Dr. Yellowlees, and Dr. Gude reported no potential conflicts of interest.

For psychiatrists embarking on a telemedicine consultation, it might be helpful to review a checklist of steps that will reduce the risk of problems when things go wrong, according to an overview of the dangers at the virtual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists, sponsored by Medscape Live.

Ideally, telepsychiatry will function much like an inpatient office visit, but the dynamics differ – as do the things that can go wrong, according to Sanjay Gupta, MD, chief medical officer, BryLin Behavioral Health System, Buffalo, N.Y. “Issues can arise suddenly. You need contingency planning.”

At the outset, psychiatrists should establish the location of the patient. This is necessary at every telemedicine encounter. With a remote device, a patient could be essentially anywhere on Earth. Patients might not even remember to mention that they are vacationing in Australia.

The location of the patient is important in the event of an unexpected crisis. This is not only relevant to an unstable patient at risk of dangerous behavior, such as actively attempting suicide, but to patients who have a seizure or some other emergency that inhibits communication. Dr. Gupta advised obtaining phone numbers for crisis services relevant to the location of the patient, and this requires confirming that the patient is where he or she was expected to be.

In addition, there should be a plan for technological failure. As everyone knows, these failures, such as dysfunction of a device, a poor connection, or an Internet outage, can happen at any time. Both the clinician and the patient can derive reassurance from at least one if not two or more plans to reconnect in the event of these failures.

The visit should also begin with questions that will establish the patient has a sense of adequate privacy. This is one of the most common obstacles to an effective telemedicine consultation. Dr. Gupta pointed out that phone or computer cameras do not typically permit the clinician to exclude the presence of another individual sitting even a few feet away from the patient. With spouses and children nearby, there might be a tenuous sense of privacy even if they are unlikely to overhear the telemedicine visit.

One strategy that can be used to assess the patient’s level of comfort is to ask for a description of the patient’s surroundings and any other people at the location. Dr. Gupta also said it is appropriate to establish ground rules about recording of the session, which has its own potential to inhibit the interaction.

Warning that some form of consent to a telemedicine visit is mandatory in most states, Dr. Gupta also cautioned that a formal identification check is appropriate for a first-time visit. The risk of an individual offering a false identification is likely to be low, but it can be eliminated entirely by a protocol that verifies consent and identify before the clinical work begins.

Because of the importance of engaging patients quickly, Dr. Gupta called the first few minutes of a telemedicine visit “crucial.” By initiating the visit with a warm and respectful tone, by relaying a competent and professional appearance, and by establishing an atmosphere that encourages communication, the initial minutes of the call can set a tone that facilitates an effective visit.

Simple and established telehealth etiquette strategies should be employed, according to Dr. Gupta. He suggested paying attention to such issues as lighting, background, and camera position. Descriptions of what constitutes adequate lighting and background are easily obtained on free how-to websites, but the goal is to provide patients with a nondistracting and clear view of the clinician.

During a telemedicine visit, the clinician’s focus should remain on the patient, according to Dr. Gupta. He advised against taking notes or documenting the visit on an electronic health record during the course of the visit. Rather, he advised positioning the camera in a way that the patient feels eye contact is being made.

“It can be helpful to periodically summarize what the patient has said to demonstrate that you are fully engaged,” Dr. Gupta suggested.

Telemedicine is very effective for many but not all patients. Some, such as those with active psychosis, are not suited to this approach, but others are simply uncomfortable with this form of communication. Dr. Gupta suggested that clinicians should be mindful of the advantages and the limitations of telepsychiatry.

Ultimately, Dr. Gupta believes that the substantial expansion of telepsychiatry that took place during the COVID-19 pandemic is likely to persist when the pandemic ends, even if many of the changes that permitted its expansion, such as a relaxation of HIPPA requirements, are withdrawn. However, parity reimbursement for visits offered by telemedicine relative to those that are face-to-face, which greatly facilitated the growth of telepsychiatry, is not guaranteed, so this remains an unanswered question.

“The question is what will happen to the billing codes when we see COVID-19 in the rearview mirror, and the answer is that no one knows,” he said.
 

Uncertainty about future use

Other experts in this field agreed. James (Jay) H. Shore, MD, MPH, director of telemedicine, Helen and Arthur E. Johnson Depression Center, University of Colorado at Denver, Aurora, has long been an advocate for the value of telepsychiatry for reaching patients with limited psychosocial services. The attention drawn to this practice by the COVID-19 pandemic has been welcome, but he does not know how it will affect the future.

“There is too much uncertainty in the system to make a good prediction of where this may end up,” he said.

It is not just reimbursement that is at risk, according to Peter Yellowlees, MBBS, MD, chief wellness officer at the University of California, Davis. Also a longtime advocate of telepsychiatry, particularly to reach the underserved, Dr. Yellowlees pointed out that the ability to prescribe controlled substances through telemedicine and the ability to consult with patients across state lines might also be in jeopardy if and when rules for telemedicine are revisited after the pandemic.

“Many organizations are lobbying to make the pandemic changes permanent because they greatly support telemedicine delivery,” Dr. Yellowlees said, but agreed about the uncertainty regarding what policy makers will do.

Jayasudha Gude, MD, who is completing her residency in psychiatry at Zucker Hillside Hospital, Northwell Health, New York, recently led a literature review evaluating the needs and viability of telepsychiatry during and after the COVID-19 era (Cureus. 2021 Aug;13:e16974). Based on the benefits she identified in her review, she said, “I would definitely want to advocate for the continued use of telepsychiatry after the pandemic is over.” She hopes that psychiatrists who now have experience in this area will join her.

“I am hopeful that a lot of mental health providers will also be advocating since they have experience, and many will want to continue its use,” she said. Medscape Live and this news organization are owned by the same parent company. Dr. Gupta, Dr. Shore, Dr. Yellowlees, and Dr. Gude reported no potential conflicts of interest.

For psychiatrists embarking on a telemedicine consultation, it might be helpful to review a checklist of steps that will reduce the risk of problems when things go wrong, according to an overview of the dangers at the virtual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists, sponsored by Medscape Live.

Ideally, telepsychiatry will function much like an inpatient office visit, but the dynamics differ – as do the things that can go wrong, according to Sanjay Gupta, MD, chief medical officer, BryLin Behavioral Health System, Buffalo, N.Y. “Issues can arise suddenly. You need contingency planning.”

At the outset, psychiatrists should establish the location of the patient. This is necessary at every telemedicine encounter. With a remote device, a patient could be essentially anywhere on Earth. Patients might not even remember to mention that they are vacationing in Australia.

The location of the patient is important in the event of an unexpected crisis. This is not only relevant to an unstable patient at risk of dangerous behavior, such as actively attempting suicide, but to patients who have a seizure or some other emergency that inhibits communication. Dr. Gupta advised obtaining phone numbers for crisis services relevant to the location of the patient, and this requires confirming that the patient is where he or she was expected to be.

In addition, there should be a plan for technological failure. As everyone knows, these failures, such as dysfunction of a device, a poor connection, or an Internet outage, can happen at any time. Both the clinician and the patient can derive reassurance from at least one if not two or more plans to reconnect in the event of these failures.

The visit should also begin with questions that will establish the patient has a sense of adequate privacy. This is one of the most common obstacles to an effective telemedicine consultation. Dr. Gupta pointed out that phone or computer cameras do not typically permit the clinician to exclude the presence of another individual sitting even a few feet away from the patient. With spouses and children nearby, there might be a tenuous sense of privacy even if they are unlikely to overhear the telemedicine visit.

One strategy that can be used to assess the patient’s level of comfort is to ask for a description of the patient’s surroundings and any other people at the location. Dr. Gupta also said it is appropriate to establish ground rules about recording of the session, which has its own potential to inhibit the interaction.

Warning that some form of consent to a telemedicine visit is mandatory in most states, Dr. Gupta also cautioned that a formal identification check is appropriate for a first-time visit. The risk of an individual offering a false identification is likely to be low, but it can be eliminated entirely by a protocol that verifies consent and identify before the clinical work begins.

Because of the importance of engaging patients quickly, Dr. Gupta called the first few minutes of a telemedicine visit “crucial.” By initiating the visit with a warm and respectful tone, by relaying a competent and professional appearance, and by establishing an atmosphere that encourages communication, the initial minutes of the call can set a tone that facilitates an effective visit.

Simple and established telehealth etiquette strategies should be employed, according to Dr. Gupta. He suggested paying attention to such issues as lighting, background, and camera position. Descriptions of what constitutes adequate lighting and background are easily obtained on free how-to websites, but the goal is to provide patients with a nondistracting and clear view of the clinician.

During a telemedicine visit, the clinician’s focus should remain on the patient, according to Dr. Gupta. He advised against taking notes or documenting the visit on an electronic health record during the course of the visit. Rather, he advised positioning the camera in a way that the patient feels eye contact is being made.

“It can be helpful to periodically summarize what the patient has said to demonstrate that you are fully engaged,” Dr. Gupta suggested.

Telemedicine is very effective for many but not all patients. Some, such as those with active psychosis, are not suited to this approach, but others are simply uncomfortable with this form of communication. Dr. Gupta suggested that clinicians should be mindful of the advantages and the limitations of telepsychiatry.

Ultimately, Dr. Gupta believes that the substantial expansion of telepsychiatry that took place during the COVID-19 pandemic is likely to persist when the pandemic ends, even if many of the changes that permitted its expansion, such as a relaxation of HIPPA requirements, are withdrawn. However, parity reimbursement for visits offered by telemedicine relative to those that are face-to-face, which greatly facilitated the growth of telepsychiatry, is not guaranteed, so this remains an unanswered question.

“The question is what will happen to the billing codes when we see COVID-19 in the rearview mirror, and the answer is that no one knows,” he said.
 

Uncertainty about future use

Other experts in this field agreed. James (Jay) H. Shore, MD, MPH, director of telemedicine, Helen and Arthur E. Johnson Depression Center, University of Colorado at Denver, Aurora, has long been an advocate for the value of telepsychiatry for reaching patients with limited psychosocial services. The attention drawn to this practice by the COVID-19 pandemic has been welcome, but he does not know how it will affect the future.

“There is too much uncertainty in the system to make a good prediction of where this may end up,” he said.

It is not just reimbursement that is at risk, according to Peter Yellowlees, MBBS, MD, chief wellness officer at the University of California, Davis. Also a longtime advocate of telepsychiatry, particularly to reach the underserved, Dr. Yellowlees pointed out that the ability to prescribe controlled substances through telemedicine and the ability to consult with patients across state lines might also be in jeopardy if and when rules for telemedicine are revisited after the pandemic.

“Many organizations are lobbying to make the pandemic changes permanent because they greatly support telemedicine delivery,” Dr. Yellowlees said, but agreed about the uncertainty regarding what policy makers will do.

Jayasudha Gude, MD, who is completing her residency in psychiatry at Zucker Hillside Hospital, Northwell Health, New York, recently led a literature review evaluating the needs and viability of telepsychiatry during and after the COVID-19 era (Cureus. 2021 Aug;13:e16974). Based on the benefits she identified in her review, she said, “I would definitely want to advocate for the continued use of telepsychiatry after the pandemic is over.” She hopes that psychiatrists who now have experience in this area will join her.

“I am hopeful that a lot of mental health providers will also be advocating since they have experience, and many will want to continue its use,” she said. Medscape Live and this news organization are owned by the same parent company. Dr. Gupta, Dr. Shore, Dr. Yellowlees, and Dr. Gude reported no potential conflicts of interest.

The use of statins by patients with rheumatoid arthritis appears to provide an overall net benefit on cardiovascular disease outcomes that outweighs the risk of type 2 diabetes mellitus (T2DM) seen with the drugs in the general population, according to evidence from a cohort study of more than 16,000 people in the United Kingdom that was presented at the virtual annual meeting of the American College of Rheumatology.

“Our study emphasizes that RA patients should be assessed for statin initiation to improve CVD risk,” lead study author Gulsen Ozen, MD, a third-year resident at the University of Nebraska, Omaha, said in an interview. Because the risk of T2DM with statin use is no worse in patients with RA than in the general population, statin initiation “is actually a great opportunity to address the risk factors for T2DM such as activity and exercise, obesity and weight loss, and [use of glucocorticoids], which have other important health effects,” she said.

“Also, importantly, even if [patients] develop T2DM, statins still work on CVD and mortality outcomes as in patients without diabetes,” Dr. Ozen added. “Given all, the benefits of statins way outweigh the hazards.”

Dr. Ozen said this was the first large cohort study to evaluate CVD mortality and T2DM risks with statins in patients with RA, a claim with which rheumatologist Elena Myasoedova, MD, PhD, of the Mayo Clinic in Rochester, Minn., concurred.

Dr. Myasoedova, professor of rheumatology and epidemiology at Mayo, said in an interview that the study was “methodologically rigorous” using time-conditional propensity score (TCPS) matching and a prevalent new-user design, “thus addressing the immortal time bias” found in the design of studies in which patients enter a cohort but do not start a treatment before developing the outcome of interest and are assigned to the untreated group or when the period of delay from when patients enter the cohort to when they are treated is excluded from the analysis. An earlier study from the same authors did not use TCPS matching, she said.

“The study findings suggest that patients with RA can benefit from statin use in terms of CVD outcomes and mortality but physicians should use vigilance regarding increased T2DM risk and discuss this possibility with patients,” Dr. Myasoedova said. “Identifying patients who are at higher risk of developing T2DM after statin initiation would be important to personalize the approach to statin therapy.”
 

Study details

The study accessed records from the U.K. Clinical Practice Research Datalink and linked Hospital Episode Statistics and Office of National Statistics databases. It analyzed adult patients with RA who were diagnosed during 1989-2018 in two cohorts: One for CVD and all-cause mortality, consisting of 1,768 statin initiators and 3,528 TCPS-matched nonusers; and a T2DM cohort with 3,608 statin initiators and 7,208 TCPS-matched nonusers.

In the entire cohort, statin use was associated with a 32% reduction in CV events (composite endpoint of the nonfatal or fatal MI, stroke, hospitalized heart failure, or CVD mortality), a 54% reduction in all-cause mortality, and a 33% increase in risk for T2DM, Dr. Ozen said. Results were similar in both sexes, although CV event reduction with statins in men did not reach statistical significance, likely because of a smaller sample size, she said.

Patients with and without a history of CVD had a similar reduction in CV events and all-cause mortality, and risk for T2DM increased with statins, but the latter reached statistical significance only in patients without a history of CVD, Dr. Ozen said.

Patients with RA who are at risk for T2DM and who are taking statins require blood glucose monitoring, which is typically done in patients with RA on disease-modifying antirheumatic drugs, and hemoglobin A1c testing when glucose levels are impaired, she said. “Any concerns for T2DM would be also communicated by the primary care providers of the patients to initiate further assessment and management,” she said.

But Dr. Ozen noted that confusion exists among primary care physicians and rheumatologists about who’s responsible for prescribing statins in these patients. “I would like to remind you that instead of assigning this role to a certain specialty, just good communication could improve this care gap of statin underutilization in RA,” she said. “Also, for rheumatologists, given that all-cause mortality reduction with statins was as high as CV event reduction, statins may be reducing other causes of mortality through improving disease activity.”

Bristol-Myers Squibb provided funding for the study. Dr. Ozen and Dr. Myasoedova have no relevant disclosures.

The use of statins by patients with rheumatoid arthritis appears to provide an overall net benefit on cardiovascular disease outcomes that outweighs the risk of type 2 diabetes mellitus (T2DM) seen with the drugs in the general population, according to evidence from a cohort study of more than 16,000 people in the United Kingdom that was presented at the virtual annual meeting of the American College of Rheumatology.

“Our study emphasizes that RA patients should be assessed for statin initiation to improve CVD risk,” lead study author Gulsen Ozen, MD, a third-year resident at the University of Nebraska, Omaha, said in an interview. Because the risk of T2DM with statin use is no worse in patients with RA than in the general population, statin initiation “is actually a great opportunity to address the risk factors for T2DM such as activity and exercise, obesity and weight loss, and [use of glucocorticoids], which have other important health effects,” she said.

“Also, importantly, even if [patients] develop T2DM, statins still work on CVD and mortality outcomes as in patients without diabetes,” Dr. Ozen added. “Given all, the benefits of statins way outweigh the hazards.”

Dr. Ozen said this was the first large cohort study to evaluate CVD mortality and T2DM risks with statins in patients with RA, a claim with which rheumatologist Elena Myasoedova, MD, PhD, of the Mayo Clinic in Rochester, Minn., concurred.

Dr. Myasoedova, professor of rheumatology and epidemiology at Mayo, said in an interview that the study was “methodologically rigorous” using time-conditional propensity score (TCPS) matching and a prevalent new-user design, “thus addressing the immortal time bias” found in the design of studies in which patients enter a cohort but do not start a treatment before developing the outcome of interest and are assigned to the untreated group or when the period of delay from when patients enter the cohort to when they are treated is excluded from the analysis. An earlier study from the same authors did not use TCPS matching, she said.

“The study findings suggest that patients with RA can benefit from statin use in terms of CVD outcomes and mortality but physicians should use vigilance regarding increased T2DM risk and discuss this possibility with patients,” Dr. Myasoedova said. “Identifying patients who are at higher risk of developing T2DM after statin initiation would be important to personalize the approach to statin therapy.”
 

Study details

The study accessed records from the U.K. Clinical Practice Research Datalink and linked Hospital Episode Statistics and Office of National Statistics databases. It analyzed adult patients with RA who were diagnosed during 1989-2018 in two cohorts: One for CVD and all-cause mortality, consisting of 1,768 statin initiators and 3,528 TCPS-matched nonusers; and a T2DM cohort with 3,608 statin initiators and 7,208 TCPS-matched nonusers.

In the entire cohort, statin use was associated with a 32% reduction in CV events (composite endpoint of the nonfatal or fatal MI, stroke, hospitalized heart failure, or CVD mortality), a 54% reduction in all-cause mortality, and a 33% increase in risk for T2DM, Dr. Ozen said. Results were similar in both sexes, although CV event reduction with statins in men did not reach statistical significance, likely because of a smaller sample size, she said.

Patients with and without a history of CVD had a similar reduction in CV events and all-cause mortality, and risk for T2DM increased with statins, but the latter reached statistical significance only in patients without a history of CVD, Dr. Ozen said.

Patients with RA who are at risk for T2DM and who are taking statins require blood glucose monitoring, which is typically done in patients with RA on disease-modifying antirheumatic drugs, and hemoglobin A1c testing when glucose levels are impaired, she said. “Any concerns for T2DM would be also communicated by the primary care providers of the patients to initiate further assessment and management,” she said.

But Dr. Ozen noted that confusion exists among primary care physicians and rheumatologists about who’s responsible for prescribing statins in these patients. “I would like to remind you that instead of assigning this role to a certain specialty, just good communication could improve this care gap of statin underutilization in RA,” she said. “Also, for rheumatologists, given that all-cause mortality reduction with statins was as high as CV event reduction, statins may be reducing other causes of mortality through improving disease activity.”

Bristol-Myers Squibb provided funding for the study. Dr. Ozen and Dr. Myasoedova have no relevant disclosures.

The use of statins by patients with rheumatoid arthritis appears to provide an overall net benefit on cardiovascular disease outcomes that outweighs the risk of type 2 diabetes mellitus (T2DM) seen with the drugs in the general population, according to evidence from a cohort study of more than 16,000 people in the United Kingdom that was presented at the virtual annual meeting of the American College of Rheumatology.

“Our study emphasizes that RA patients should be assessed for statin initiation to improve CVD risk,” lead study author Gulsen Ozen, MD, a third-year resident at the University of Nebraska, Omaha, said in an interview. Because the risk of T2DM with statin use is no worse in patients with RA than in the general population, statin initiation “is actually a great opportunity to address the risk factors for T2DM such as activity and exercise, obesity and weight loss, and [use of glucocorticoids], which have other important health effects,” she said.

“Also, importantly, even if [patients] develop T2DM, statins still work on CVD and mortality outcomes as in patients without diabetes,” Dr. Ozen added. “Given all, the benefits of statins way outweigh the hazards.”

Dr. Ozen said this was the first large cohort study to evaluate CVD mortality and T2DM risks with statins in patients with RA, a claim with which rheumatologist Elena Myasoedova, MD, PhD, of the Mayo Clinic in Rochester, Minn., concurred.

Dr. Myasoedova, professor of rheumatology and epidemiology at Mayo, said in an interview that the study was “methodologically rigorous” using time-conditional propensity score (TCPS) matching and a prevalent new-user design, “thus addressing the immortal time bias” found in the design of studies in which patients enter a cohort but do not start a treatment before developing the outcome of interest and are assigned to the untreated group or when the period of delay from when patients enter the cohort to when they are treated is excluded from the analysis. An earlier study from the same authors did not use TCPS matching, she said.

“The study findings suggest that patients with RA can benefit from statin use in terms of CVD outcomes and mortality but physicians should use vigilance regarding increased T2DM risk and discuss this possibility with patients,” Dr. Myasoedova said. “Identifying patients who are at higher risk of developing T2DM after statin initiation would be important to personalize the approach to statin therapy.”
 

Study details

The study accessed records from the U.K. Clinical Practice Research Datalink and linked Hospital Episode Statistics and Office of National Statistics databases. It analyzed adult patients with RA who were diagnosed during 1989-2018 in two cohorts: One for CVD and all-cause mortality, consisting of 1,768 statin initiators and 3,528 TCPS-matched nonusers; and a T2DM cohort with 3,608 statin initiators and 7,208 TCPS-matched nonusers.

In the entire cohort, statin use was associated with a 32% reduction in CV events (composite endpoint of the nonfatal or fatal MI, stroke, hospitalized heart failure, or CVD mortality), a 54% reduction in all-cause mortality, and a 33% increase in risk for T2DM, Dr. Ozen said. Results were similar in both sexes, although CV event reduction with statins in men did not reach statistical significance, likely because of a smaller sample size, she said.

Patients with and without a history of CVD had a similar reduction in CV events and all-cause mortality, and risk for T2DM increased with statins, but the latter reached statistical significance only in patients without a history of CVD, Dr. Ozen said.

Patients with RA who are at risk for T2DM and who are taking statins require blood glucose monitoring, which is typically done in patients with RA on disease-modifying antirheumatic drugs, and hemoglobin A1c testing when glucose levels are impaired, she said. “Any concerns for T2DM would be also communicated by the primary care providers of the patients to initiate further assessment and management,” she said.

But Dr. Ozen noted that confusion exists among primary care physicians and rheumatologists about who’s responsible for prescribing statins in these patients. “I would like to remind you that instead of assigning this role to a certain specialty, just good communication could improve this care gap of statin underutilization in RA,” she said. “Also, for rheumatologists, given that all-cause mortality reduction with statins was as high as CV event reduction, statins may be reducing other causes of mortality through improving disease activity.”

Bristol-Myers Squibb provided funding for the study. Dr. Ozen and Dr. Myasoedova have no relevant disclosures.

Just months after the MASTER DAPT trial showed that abbreviated dual-antiplatelet therapy (DAPT) lowers the risk of bleeding after stent placement in patients at high bleeding risk, a new analysis showed the favorable benefit-to-risk ratio was about the same in the subgroup who also had an acute or recent myocardial infarction.

In the new prespecified MASTER DAPT analysis, the data show that the subgroup with both an increased bleeding risk and an increased risk of ischemic events benefited much like the entire study population from a shorter DAPT duration, reported Pieter C. Smits, MD, PhD, at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.

“There was no signal towards increased ischemic risk in the abbreviated DAPT population presenting with recent acute MI,” said Dr. Smits, emphasizing the consistency of results in this “bi-risk” subgroup with objective criteria for increased risks of bleeding and ischemic events.

MASTER DAPT main results published

The main results of the MASTER DAPT trial were presented at the 2021 annual meeting of the European Society of Cardiology and published recently in the New England Journal of Medicine. The trial randomized 4,434 patients who met one or more criteria for high bleeding risk. These included age of at least 75 years, documented anemia, a clinical indication for oral anticoagulants, and previous bleeding episodes requiring hospitalization.

In the trial, all patients were maintained on DAPT for 1 month after implantation of a biodegradable-polymer, sirolimus-eluting coronary stent (Ultimaster, Terumo). At the end of the month, those randomized to abbreviated DAPT started immediately on single-agent antiplatelet therapy, while those in the standard DAPT group remained on DAPT for at least 2 additional months.

Over 1 year of follow-up, the bleeding event rate was lower in the abbreviated DAPT group (6.5% vs. 9.4%; P < .0001 for superiority). The slight increase in major ischemic events among those in the abbreviated DAPT group (6.1% vs. 5.9%) was not significantly different (P = .001 for noninferiority).

When compared on the basis of net adverse clinical events (NACE), which comprised all-case death, MI, stroke, or Bleeding Academic Research Consortium (BARC) level 3 or 5 bleeding, there was a slight advantage for abbreviated DAPT (7.5% vs. 7.7%). This did not reach significance, but it was similar (P < .001 for noninferiority), favoring the abbreviated course of DAPT because of the bleeding advantage.

Recent MI vs. no MI

In the new analysis, patients in both the abbreviated and standard DAPT group were stratified into those with no major cardiovascular event within the past 12 months and those with an acute MI or acute coronary syndrome within this time. There were somewhat more patients without a history of MI within the previous 12 months in both the abbreviated DAPT (1,381 vs. 914 patients) and standard DAPT (1,418 vs. 866) groups.

In those without a recent MI, NACE rates were nearly identical over 1-year follow-up for those who received abbreviated versus standard DAPT. In both, slightly more than 6% had a NACE event, producing a hazard ratio of 1.03 for abbreviated versus standard DAPT (P = 0.85).

For those with a recent MI, event rates began to separate within 30 days. By 1 year, NACE rates exceeded 10% in those on standard DAPT, but remained below 9% for those on abbreviated DAPT. The lower hazard ratio in the abbreviated DAPT group (HR, 0.83; P = .22) did not reach statistical significance, but it did echo the larger MASTER DAPT conclusion.

“An abbreviated DAPT strategy significantly reduced clinically relevant bleeding risk in these bi-risk patients without increasing risk of ischemic events,” reported Dr. Smits, director of interventional cardiology at Maasstad Hospital, Rotterdam, the Netherlands.
 

No difference in NACE components

In fact, when the components of NACE were evaluated individually in the subgroup of patients with prior MI, both stroke (HR, 0.47; P = .16) and all-cause death (HR, 0.78; P = .28), although not significant, numerically favored abbreviated DAPT.

There was no difference between abbreviated and standard DAPT for risk of MI at 1 year (HR, 1.03; P = .92).

As in the overall MASTER DAPT results, bleeding risk (BARC 2, 3, or 5 bleeding) was significantly reduced in the substudy among those with a recent prior MI (P = .013) or those with no MI in the prior 12 months (P = .01).

In MASTER DAPT, which was an open-label study that randomized participants in 30 countries, all patients received one type of drug-eluting stent. While Dr. Smits conceded that it is not clear whether the conclusions about abbreviated DAPT can be extrapolated to other stents, he noted that recent long-term outcomes for modern drug-eluting coronary stents have been similar, suggesting these results might be more broadly applicable.

According to Dr. Smit, the consistency of this subgroup analysis with the previously published MASTER DAPT study is mutually reinforcing for a role of abbreviated DAPT in patients at high bleeding risk. Other experts agreed.

“One of the concerns that people have had is exactly what has been addressed here in this subgroup analysis. These are the patients that are not only bleeding-risk high but ischemic-risk high. The question was whether the benefit of reducing bleeding risk is offset by increasing stent thrombosis or other ischemic event outcomes, and the answer from the analysis is really clearly no,” said Philippe Gabriel Steg, MD, chief, department of cardiology, Hôpital Bichat, Paris, at the meeting, sponsored by the Cardiovascular Research Foundation.

Dr. Smits reports financial relationships with Abiomed, Abbott Vascular, Daiichi-Sankyo, Microport, Opsense, and Terumo Medical. Dr. Steg reports financial relationships with Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Idorsia, Merck, Novartis, Regeneron, and Sanofi-Aventis.

Just months after the MASTER DAPT trial showed that abbreviated dual-antiplatelet therapy (DAPT) lowers the risk of bleeding after stent placement in patients at high bleeding risk, a new analysis showed the favorable benefit-to-risk ratio was about the same in the subgroup who also had an acute or recent myocardial infarction.

In the new prespecified MASTER DAPT analysis, the data show that the subgroup with both an increased bleeding risk and an increased risk of ischemic events benefited much like the entire study population from a shorter DAPT duration, reported Pieter C. Smits, MD, PhD, at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.

“There was no signal towards increased ischemic risk in the abbreviated DAPT population presenting with recent acute MI,” said Dr. Smits, emphasizing the consistency of results in this “bi-risk” subgroup with objective criteria for increased risks of bleeding and ischemic events.

MASTER DAPT main results published

The main results of the MASTER DAPT trial were presented at the 2021 annual meeting of the European Society of Cardiology and published recently in the New England Journal of Medicine. The trial randomized 4,434 patients who met one or more criteria for high bleeding risk. These included age of at least 75 years, documented anemia, a clinical indication for oral anticoagulants, and previous bleeding episodes requiring hospitalization.

In the trial, all patients were maintained on DAPT for 1 month after implantation of a biodegradable-polymer, sirolimus-eluting coronary stent (Ultimaster, Terumo). At the end of the month, those randomized to abbreviated DAPT started immediately on single-agent antiplatelet therapy, while those in the standard DAPT group remained on DAPT for at least 2 additional months.

Over 1 year of follow-up, the bleeding event rate was lower in the abbreviated DAPT group (6.5% vs. 9.4%; P < .0001 for superiority). The slight increase in major ischemic events among those in the abbreviated DAPT group (6.1% vs. 5.9%) was not significantly different (P = .001 for noninferiority).

When compared on the basis of net adverse clinical events (NACE), which comprised all-case death, MI, stroke, or Bleeding Academic Research Consortium (BARC) level 3 or 5 bleeding, there was a slight advantage for abbreviated DAPT (7.5% vs. 7.7%). This did not reach significance, but it was similar (P < .001 for noninferiority), favoring the abbreviated course of DAPT because of the bleeding advantage.

Recent MI vs. no MI

In the new analysis, patients in both the abbreviated and standard DAPT group were stratified into those with no major cardiovascular event within the past 12 months and those with an acute MI or acute coronary syndrome within this time. There were somewhat more patients without a history of MI within the previous 12 months in both the abbreviated DAPT (1,381 vs. 914 patients) and standard DAPT (1,418 vs. 866) groups.

In those without a recent MI, NACE rates were nearly identical over 1-year follow-up for those who received abbreviated versus standard DAPT. In both, slightly more than 6% had a NACE event, producing a hazard ratio of 1.03 for abbreviated versus standard DAPT (P = 0.85).

For those with a recent MI, event rates began to separate within 30 days. By 1 year, NACE rates exceeded 10% in those on standard DAPT, but remained below 9% for those on abbreviated DAPT. The lower hazard ratio in the abbreviated DAPT group (HR, 0.83; P = .22) did not reach statistical significance, but it did echo the larger MASTER DAPT conclusion.

“An abbreviated DAPT strategy significantly reduced clinically relevant bleeding risk in these bi-risk patients without increasing risk of ischemic events,” reported Dr. Smits, director of interventional cardiology at Maasstad Hospital, Rotterdam, the Netherlands.
 

No difference in NACE components

In fact, when the components of NACE were evaluated individually in the subgroup of patients with prior MI, both stroke (HR, 0.47; P = .16) and all-cause death (HR, 0.78; P = .28), although not significant, numerically favored abbreviated DAPT.

There was no difference between abbreviated and standard DAPT for risk of MI at 1 year (HR, 1.03; P = .92).

As in the overall MASTER DAPT results, bleeding risk (BARC 2, 3, or 5 bleeding) was significantly reduced in the substudy among those with a recent prior MI (P = .013) or those with no MI in the prior 12 months (P = .01).

In MASTER DAPT, which was an open-label study that randomized participants in 30 countries, all patients received one type of drug-eluting stent. While Dr. Smits conceded that it is not clear whether the conclusions about abbreviated DAPT can be extrapolated to other stents, he noted that recent long-term outcomes for modern drug-eluting coronary stents have been similar, suggesting these results might be more broadly applicable.

According to Dr. Smit, the consistency of this subgroup analysis with the previously published MASTER DAPT study is mutually reinforcing for a role of abbreviated DAPT in patients at high bleeding risk. Other experts agreed.

“One of the concerns that people have had is exactly what has been addressed here in this subgroup analysis. These are the patients that are not only bleeding-risk high but ischemic-risk high. The question was whether the benefit of reducing bleeding risk is offset by increasing stent thrombosis or other ischemic event outcomes, and the answer from the analysis is really clearly no,” said Philippe Gabriel Steg, MD, chief, department of cardiology, Hôpital Bichat, Paris, at the meeting, sponsored by the Cardiovascular Research Foundation.

Dr. Smits reports financial relationships with Abiomed, Abbott Vascular, Daiichi-Sankyo, Microport, Opsense, and Terumo Medical. Dr. Steg reports financial relationships with Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Idorsia, Merck, Novartis, Regeneron, and Sanofi-Aventis.

Just months after the MASTER DAPT trial showed that abbreviated dual-antiplatelet therapy (DAPT) lowers the risk of bleeding after stent placement in patients at high bleeding risk, a new analysis showed the favorable benefit-to-risk ratio was about the same in the subgroup who also had an acute or recent myocardial infarction.

In the new prespecified MASTER DAPT analysis, the data show that the subgroup with both an increased bleeding risk and an increased risk of ischemic events benefited much like the entire study population from a shorter DAPT duration, reported Pieter C. Smits, MD, PhD, at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.

“There was no signal towards increased ischemic risk in the abbreviated DAPT population presenting with recent acute MI,” said Dr. Smits, emphasizing the consistency of results in this “bi-risk” subgroup with objective criteria for increased risks of bleeding and ischemic events.

MASTER DAPT main results published

The main results of the MASTER DAPT trial were presented at the 2021 annual meeting of the European Society of Cardiology and published recently in the New England Journal of Medicine. The trial randomized 4,434 patients who met one or more criteria for high bleeding risk. These included age of at least 75 years, documented anemia, a clinical indication for oral anticoagulants, and previous bleeding episodes requiring hospitalization.

In the trial, all patients were maintained on DAPT for 1 month after implantation of a biodegradable-polymer, sirolimus-eluting coronary stent (Ultimaster, Terumo). At the end of the month, those randomized to abbreviated DAPT started immediately on single-agent antiplatelet therapy, while those in the standard DAPT group remained on DAPT for at least 2 additional months.

Over 1 year of follow-up, the bleeding event rate was lower in the abbreviated DAPT group (6.5% vs. 9.4%; P < .0001 for superiority). The slight increase in major ischemic events among those in the abbreviated DAPT group (6.1% vs. 5.9%) was not significantly different (P = .001 for noninferiority).

When compared on the basis of net adverse clinical events (NACE), which comprised all-case death, MI, stroke, or Bleeding Academic Research Consortium (BARC) level 3 or 5 bleeding, there was a slight advantage for abbreviated DAPT (7.5% vs. 7.7%). This did not reach significance, but it was similar (P < .001 for noninferiority), favoring the abbreviated course of DAPT because of the bleeding advantage.

Recent MI vs. no MI

In the new analysis, patients in both the abbreviated and standard DAPT group were stratified into those with no major cardiovascular event within the past 12 months and those with an acute MI or acute coronary syndrome within this time. There were somewhat more patients without a history of MI within the previous 12 months in both the abbreviated DAPT (1,381 vs. 914 patients) and standard DAPT (1,418 vs. 866) groups.

In those without a recent MI, NACE rates were nearly identical over 1-year follow-up for those who received abbreviated versus standard DAPT. In both, slightly more than 6% had a NACE event, producing a hazard ratio of 1.03 for abbreviated versus standard DAPT (P = 0.85).

For those with a recent MI, event rates began to separate within 30 days. By 1 year, NACE rates exceeded 10% in those on standard DAPT, but remained below 9% for those on abbreviated DAPT. The lower hazard ratio in the abbreviated DAPT group (HR, 0.83; P = .22) did not reach statistical significance, but it did echo the larger MASTER DAPT conclusion.

“An abbreviated DAPT strategy significantly reduced clinically relevant bleeding risk in these bi-risk patients without increasing risk of ischemic events,” reported Dr. Smits, director of interventional cardiology at Maasstad Hospital, Rotterdam, the Netherlands.
 

No difference in NACE components

In fact, when the components of NACE were evaluated individually in the subgroup of patients with prior MI, both stroke (HR, 0.47; P = .16) and all-cause death (HR, 0.78; P = .28), although not significant, numerically favored abbreviated DAPT.

There was no difference between abbreviated and standard DAPT for risk of MI at 1 year (HR, 1.03; P = .92).

As in the overall MASTER DAPT results, bleeding risk (BARC 2, 3, or 5 bleeding) was significantly reduced in the substudy among those with a recent prior MI (P = .013) or those with no MI in the prior 12 months (P = .01).

In MASTER DAPT, which was an open-label study that randomized participants in 30 countries, all patients received one type of drug-eluting stent. While Dr. Smits conceded that it is not clear whether the conclusions about abbreviated DAPT can be extrapolated to other stents, he noted that recent long-term outcomes for modern drug-eluting coronary stents have been similar, suggesting these results might be more broadly applicable.

According to Dr. Smit, the consistency of this subgroup analysis with the previously published MASTER DAPT study is mutually reinforcing for a role of abbreviated DAPT in patients at high bleeding risk. Other experts agreed.

“One of the concerns that people have had is exactly what has been addressed here in this subgroup analysis. These are the patients that are not only bleeding-risk high but ischemic-risk high. The question was whether the benefit of reducing bleeding risk is offset by increasing stent thrombosis or other ischemic event outcomes, and the answer from the analysis is really clearly no,” said Philippe Gabriel Steg, MD, chief, department of cardiology, Hôpital Bichat, Paris, at the meeting, sponsored by the Cardiovascular Research Foundation.

Dr. Smits reports financial relationships with Abiomed, Abbott Vascular, Daiichi-Sankyo, Microport, Opsense, and Terumo Medical. Dr. Steg reports financial relationships with Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Idorsia, Merck, Novartis, Regeneron, and Sanofi-Aventis.

Among patients with the recently defined severe autoinflammatory syndrome VEXAS, those who are transfusion dependent or have a specific amino acid substitution are at highest risk for death, whereas those with ear chondritis are at significantly lower risk, a multinational team of investigators has found.

Courtesy Dr. Marcela Ferrada

Their study of mortality and predictors of survival among patients with genetically confirmed VEXAS showed that patients with a VEXAS variant resulting in an amino acid substitution of a methionine for a valine had a 3.5-fold higher risk for death, compared with patients with either a methionine-to-threonine substitution or a methionine-to-leucine swap.

Transfusion dependence was an independent predictor of mortality. Patients who became dependent on transfusions after symptom onset had a nearly threefold higher risk for death, reported Marcela A. Ferrada, MD, a clinical fellow at the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

“These findings should inform risk assessment and clinical management in patients with VEXAS syndrome,” she said in an oral abstract presentation during the virtual annual meeting of the American College of Rheumatology.

“These genetic findings have proven right now to be not only diagnostic, but we have shown that they’re also prognostic, and we hope that this is going to help us identify patients who could have more aggressive treatment,” Dr. Ferrada said.

She also discussed her findings in a media briefing held 2 days prior to her plenary presentation. At that briefing, this news organization asked participating clinicians whether they had patients who they suspected may have had undiagnosed VEXAS.

“My answer to that is interesting,” replied moderator Vaneet Sandhu, MD, from Loma Linda (Calif.) University and Riverside University Health System.

“In the last couple of days, I’ve been reading about VEXAS, and actually texted one of my colleagues yesterday and said, ‘Hey, you know these patients we’ve been seeing who have these strange rashes and chondritis and have maybe a diagnosis of leukocytoclastic vasculitis or something else – are we not diagnosing these patients?’ ” she said.

“I think we are looking at every patient with chondritis and reexamining their phenotype. We had dismissed certain symptoms because they didn’t fit the archetype for relapsing polychondritis, for example, but it could be VEXAS,” said Alfred Kim, MD, PhD, of Washington University in St. Louis, who also presented data during the briefing.

Three variants

VEXAS is caused by somatic mutations in UBA1, a gene that initiates cytoplasmic ubiquitylation, a process by which misfolded proteins are tagged for degradation.

The syndrome’s name is an acronym descriptive of the major features:

• Vacuoles in bone marrow cells.
• E-1 activating enzyme that UBA1 encodes for.
• X-linked.
• Autoinflammatory.
• Somatic mutation featuring hematologic mosaicism.

VEXAS results in rheumatologic, dermatologic, and hematologic symptoms that are often misdiagnosed as being caused by treatment-refractory relapsing polychondritis, polyarteritis nodosa, Sweet syndrome, giant cell arteritis, or myelodysplastic syndrome (MDS).

VEXAS was identified as a distinct syndrome within the past year by Dr. Ferrada and other investigators at NIAMS, the National Human Genome Research Institute, and other institutions.

In the study reported at ACR 2021, Dr. Ferrada and colleagues assessed 83 men who had been referred for genetic testing for VEXAS at the National Institutes of Health, in Bethesda, Md., and at Leeds (England) Teaching Hospitals NHS Trust.

All patients were confirmed to have VEXAS-defining genetic mutations in UBA1 by Sanger sequencing of peripheral blood samples. Only those patients with mutations at codon p.Met41 were included in the investigators’ analysis. Mutations at that site account for nearly all cases of VEXAS that have been identified to date.

The most common clinical manifestation of VEXAS was skin involvement, which occurred in all but one of the 83 patients. Other common manifestations included arthritis (58 patients), pulmonary infiltrates (57 patients), and ear chondritis (54 patients).

Fifteen patients were found to have the leucine variant, 18 had the valine variant, and 50 had the threonine variant. The median age at disease onset was 66 years in the leucine and threonine variant groups and 65 in the valine variant group.

The clinical diagnosis differed according to genotype: 4 of 18 patients (22%) with the valine variant were diagnosed with relapsing polychondritis, compared with 8 of 15 (53%) with the leucine variant and 31 of 50 (62%) with the threonine variant (P = .01).

In contrast, 55% of patients with valine genotype were diagnosed with undifferentiated fever, compared with 6% of those with the leucine and 16% with the threonine genotypes (P = .001). More patients with the leucine variant (60%) were diagnosed with Sweet syndrome, compared with 11% and 14% of patients with the valine and threonine variants, respectively (P = .001).

There was no significant difference among the three genotypes in the percentage of patients diagnosed with MDS.

The follow-up period ranged from 1 to 18 years (median, 4.7 years). The median survival time from disease onset for all patients was 10 years.

Among patients with the valine variant, median survival was 9 years, which was significantly less than among patients with the other two variants (P = .01).

In univariable analysis, independent predictors of mortality were ear chondritis (hazard ratio, 0.26; P = .005), transfusion dependence, a time-dependent variable (HR, 2.59; P = .03), and the valine variant (HR, 3.5; P = .008).

The association between VEXAS genotype and phenotype could be explained by the finding that, among patients with the valine variant, there was significantly less translation of the catalytically proficient UBA1b isoform than in patients with the other two variants, Dr. Ferrada said.

Therapeutic options

Dr. Ferrada noted that to date no drugs have been shown to provide consistent therapeutic benefits for patients with VEXAS, but evidence as to the etiology of the syndrome points to possible treatment approaches.

“All of these findings I think are extremely important to help us guide management of these patients, as we know that the mutation is located in the stem cells in the bone marrow. So we suspect that doing a bone marrow transplant in these patients is going to be curative,” Dr. Ferrada said during the briefing.

Investigators are planning a phase 2 trial of allogeneic hematopoietic stem cell transplant for patients with VEXAS.

The study was supported by the National Institutes of Health. Dr. Ferrada, Dr. Sandhu, and Dr. Kim have disclosed no relevant financial relationships.

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

Among patients with the recently defined severe autoinflammatory syndrome VEXAS, those who are transfusion dependent or have a specific amino acid substitution are at highest risk for death, whereas those with ear chondritis are at significantly lower risk, a multinational team of investigators has found.

Courtesy Dr. Marcela Ferrada

Their study of mortality and predictors of survival among patients with genetically confirmed VEXAS showed that patients with a VEXAS variant resulting in an amino acid substitution of a methionine for a valine had a 3.5-fold higher risk for death, compared with patients with either a methionine-to-threonine substitution or a methionine-to-leucine swap.

Transfusion dependence was an independent predictor of mortality. Patients who became dependent on transfusions after symptom onset had a nearly threefold higher risk for death, reported Marcela A. Ferrada, MD, a clinical fellow at the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

“These findings should inform risk assessment and clinical management in patients with VEXAS syndrome,” she said in an oral abstract presentation during the virtual annual meeting of the American College of Rheumatology.

“These genetic findings have proven right now to be not only diagnostic, but we have shown that they’re also prognostic, and we hope that this is going to help us identify patients who could have more aggressive treatment,” Dr. Ferrada said.

She also discussed her findings in a media briefing held 2 days prior to her plenary presentation. At that briefing, this news organization asked participating clinicians whether they had patients who they suspected may have had undiagnosed VEXAS.

“My answer to that is interesting,” replied moderator Vaneet Sandhu, MD, from Loma Linda (Calif.) University and Riverside University Health System.

“In the last couple of days, I’ve been reading about VEXAS, and actually texted one of my colleagues yesterday and said, ‘Hey, you know these patients we’ve been seeing who have these strange rashes and chondritis and have maybe a diagnosis of leukocytoclastic vasculitis or something else – are we not diagnosing these patients?’ ” she said.

“I think we are looking at every patient with chondritis and reexamining their phenotype. We had dismissed certain symptoms because they didn’t fit the archetype for relapsing polychondritis, for example, but it could be VEXAS,” said Alfred Kim, MD, PhD, of Washington University in St. Louis, who also presented data during the briefing.

Three variants

VEXAS is caused by somatic mutations in UBA1, a gene that initiates cytoplasmic ubiquitylation, a process by which misfolded proteins are tagged for degradation.

The syndrome’s name is an acronym descriptive of the major features:

• Vacuoles in bone marrow cells.
• E-1 activating enzyme that UBA1 encodes for.
• X-linked.
• Autoinflammatory.
• Somatic mutation featuring hematologic mosaicism.

VEXAS results in rheumatologic, dermatologic, and hematologic symptoms that are often misdiagnosed as being caused by treatment-refractory relapsing polychondritis, polyarteritis nodosa, Sweet syndrome, giant cell arteritis, or myelodysplastic syndrome (MDS).

VEXAS was identified as a distinct syndrome within the past year by Dr. Ferrada and other investigators at NIAMS, the National Human Genome Research Institute, and other institutions.

In the study reported at ACR 2021, Dr. Ferrada and colleagues assessed 83 men who had been referred for genetic testing for VEXAS at the National Institutes of Health, in Bethesda, Md., and at Leeds (England) Teaching Hospitals NHS Trust.

All patients were confirmed to have VEXAS-defining genetic mutations in UBA1 by Sanger sequencing of peripheral blood samples. Only those patients with mutations at codon p.Met41 were included in the investigators’ analysis. Mutations at that site account for nearly all cases of VEXAS that have been identified to date.

The most common clinical manifestation of VEXAS was skin involvement, which occurred in all but one of the 83 patients. Other common manifestations included arthritis (58 patients), pulmonary infiltrates (57 patients), and ear chondritis (54 patients).

Fifteen patients were found to have the leucine variant, 18 had the valine variant, and 50 had the threonine variant. The median age at disease onset was 66 years in the leucine and threonine variant groups and 65 in the valine variant group.

The clinical diagnosis differed according to genotype: 4 of 18 patients (22%) with the valine variant were diagnosed with relapsing polychondritis, compared with 8 of 15 (53%) with the leucine variant and 31 of 50 (62%) with the threonine variant (P = .01).

In contrast, 55% of patients with valine genotype were diagnosed with undifferentiated fever, compared with 6% of those with the leucine and 16% with the threonine genotypes (P = .001). More patients with the leucine variant (60%) were diagnosed with Sweet syndrome, compared with 11% and 14% of patients with the valine and threonine variants, respectively (P = .001).

There was no significant difference among the three genotypes in the percentage of patients diagnosed with MDS.

The follow-up period ranged from 1 to 18 years (median, 4.7 years). The median survival time from disease onset for all patients was 10 years.

Among patients with the valine variant, median survival was 9 years, which was significantly less than among patients with the other two variants (P = .01).

In univariable analysis, independent predictors of mortality were ear chondritis (hazard ratio, 0.26; P = .005), transfusion dependence, a time-dependent variable (HR, 2.59; P = .03), and the valine variant (HR, 3.5; P = .008).

The association between VEXAS genotype and phenotype could be explained by the finding that, among patients with the valine variant, there was significantly less translation of the catalytically proficient UBA1b isoform than in patients with the other two variants, Dr. Ferrada said.

Therapeutic options

Dr. Ferrada noted that to date no drugs have been shown to provide consistent therapeutic benefits for patients with VEXAS, but evidence as to the etiology of the syndrome points to possible treatment approaches.

“All of these findings I think are extremely important to help us guide management of these patients, as we know that the mutation is located in the stem cells in the bone marrow. So we suspect that doing a bone marrow transplant in these patients is going to be curative,” Dr. Ferrada said during the briefing.

Investigators are planning a phase 2 trial of allogeneic hematopoietic stem cell transplant for patients with VEXAS.

The study was supported by the National Institutes of Health. Dr. Ferrada, Dr. Sandhu, and Dr. Kim have disclosed no relevant financial relationships.

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

Among patients with the recently defined severe autoinflammatory syndrome VEXAS, those who are transfusion dependent or have a specific amino acid substitution are at highest risk for death, whereas those with ear chondritis are at significantly lower risk, a multinational team of investigators has found.

Courtesy Dr. Marcela Ferrada

Their study of mortality and predictors of survival among patients with genetically confirmed VEXAS showed that patients with a VEXAS variant resulting in an amino acid substitution of a methionine for a valine had a 3.5-fold higher risk for death, compared with patients with either a methionine-to-threonine substitution or a methionine-to-leucine swap.

Transfusion dependence was an independent predictor of mortality. Patients who became dependent on transfusions after symptom onset had a nearly threefold higher risk for death, reported Marcela A. Ferrada, MD, a clinical fellow at the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

“These findings should inform risk assessment and clinical management in patients with VEXAS syndrome,” she said in an oral abstract presentation during the virtual annual meeting of the American College of Rheumatology.

“These genetic findings have proven right now to be not only diagnostic, but we have shown that they’re also prognostic, and we hope that this is going to help us identify patients who could have more aggressive treatment,” Dr. Ferrada said.

She also discussed her findings in a media briefing held 2 days prior to her plenary presentation. At that briefing, this news organization asked participating clinicians whether they had patients who they suspected may have had undiagnosed VEXAS.

“My answer to that is interesting,” replied moderator Vaneet Sandhu, MD, from Loma Linda (Calif.) University and Riverside University Health System.

“In the last couple of days, I’ve been reading about VEXAS, and actually texted one of my colleagues yesterday and said, ‘Hey, you know these patients we’ve been seeing who have these strange rashes and chondritis and have maybe a diagnosis of leukocytoclastic vasculitis or something else – are we not diagnosing these patients?’ ” she said.

“I think we are looking at every patient with chondritis and reexamining their phenotype. We had dismissed certain symptoms because they didn’t fit the archetype for relapsing polychondritis, for example, but it could be VEXAS,” said Alfred Kim, MD, PhD, of Washington University in St. Louis, who also presented data during the briefing.

Three variants

VEXAS is caused by somatic mutations in UBA1, a gene that initiates cytoplasmic ubiquitylation, a process by which misfolded proteins are tagged for degradation.

The syndrome’s name is an acronym descriptive of the major features:

• Vacuoles in bone marrow cells.
• E-1 activating enzyme that UBA1 encodes for.
• X-linked.
• Autoinflammatory.
• Somatic mutation featuring hematologic mosaicism.

VEXAS results in rheumatologic, dermatologic, and hematologic symptoms that are often misdiagnosed as being caused by treatment-refractory relapsing polychondritis, polyarteritis nodosa, Sweet syndrome, giant cell arteritis, or myelodysplastic syndrome (MDS).

VEXAS was identified as a distinct syndrome within the past year by Dr. Ferrada and other investigators at NIAMS, the National Human Genome Research Institute, and other institutions.

In the study reported at ACR 2021, Dr. Ferrada and colleagues assessed 83 men who had been referred for genetic testing for VEXAS at the National Institutes of Health, in Bethesda, Md., and at Leeds (England) Teaching Hospitals NHS Trust.

All patients were confirmed to have VEXAS-defining genetic mutations in UBA1 by Sanger sequencing of peripheral blood samples. Only those patients with mutations at codon p.Met41 were included in the investigators’ analysis. Mutations at that site account for nearly all cases of VEXAS that have been identified to date.

The most common clinical manifestation of VEXAS was skin involvement, which occurred in all but one of the 83 patients. Other common manifestations included arthritis (58 patients), pulmonary infiltrates (57 patients), and ear chondritis (54 patients).

Fifteen patients were found to have the leucine variant, 18 had the valine variant, and 50 had the threonine variant. The median age at disease onset was 66 years in the leucine and threonine variant groups and 65 in the valine variant group.

The clinical diagnosis differed according to genotype: 4 of 18 patients (22%) with the valine variant were diagnosed with relapsing polychondritis, compared with 8 of 15 (53%) with the leucine variant and 31 of 50 (62%) with the threonine variant (P = .01).

In contrast, 55% of patients with valine genotype were diagnosed with undifferentiated fever, compared with 6% of those with the leucine and 16% with the threonine genotypes (P = .001). More patients with the leucine variant (60%) were diagnosed with Sweet syndrome, compared with 11% and 14% of patients with the valine and threonine variants, respectively (P = .001).

There was no significant difference among the three genotypes in the percentage of patients diagnosed with MDS.

The follow-up period ranged from 1 to 18 years (median, 4.7 years). The median survival time from disease onset for all patients was 10 years.

Among patients with the valine variant, median survival was 9 years, which was significantly less than among patients with the other two variants (P = .01).

In univariable analysis, independent predictors of mortality were ear chondritis (hazard ratio, 0.26; P = .005), transfusion dependence, a time-dependent variable (HR, 2.59; P = .03), and the valine variant (HR, 3.5; P = .008).

The association between VEXAS genotype and phenotype could be explained by the finding that, among patients with the valine variant, there was significantly less translation of the catalytically proficient UBA1b isoform than in patients with the other two variants, Dr. Ferrada said.

Therapeutic options

Dr. Ferrada noted that to date no drugs have been shown to provide consistent therapeutic benefits for patients with VEXAS, but evidence as to the etiology of the syndrome points to possible treatment approaches.

“All of these findings I think are extremely important to help us guide management of these patients, as we know that the mutation is located in the stem cells in the bone marrow. So we suspect that doing a bone marrow transplant in these patients is going to be curative,” Dr. Ferrada said during the briefing.

Investigators are planning a phase 2 trial of allogeneic hematopoietic stem cell transplant for patients with VEXAS.

The study was supported by the National Institutes of Health. Dr. Ferrada, Dr. Sandhu, and Dr. Kim have disclosed no relevant financial relationships.

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