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Anti-TNF Exposure Influences Efficacy of Subsequent Therapies in UC
, based on results of a large meta-analysis.
Patients previously treated with TNF antagonists were less likely to respond to lymphocyte trafficking inhibitors but more likely to achieve remission on Janus kinase (JAK) inhibitors, Han Hee Lee, MD, PhD, of the University of California San Diego, and colleagues reported.
“Treatment options for patients with moderate-severe ulcerative colitis have increased in the last decade with the availability of six different classes of medications,” investigators wrote in Clinical Gastroenterology and Hepatology (2024 Dec. doi:10.1016/j.cgh.2024.12.007). “There is wide interindividual variability in response to specific medications, and drivers of this heterogeneity are critical to understand to be able to choose the best therapy for each individual patient.”
To learn more about the impacts of anti-TNF exposure on subsequent advanced therapies, the investigators conducted a systematic review and meta-analysis of 17 phase 2 and 3 trials. The dataset included 8,871 adults with moderate-severe UC.
The primary outcome was induction of clinical remission at 6–14 weeks, most often defined as a Mayo Clinic score of 2 or lower with no subscore greater than 1. Endoscopic improvement, generally defined as a Mayo endoscopic subscore of 0 or 1, was evaluated as a secondary endpoint.
Advanced therapies were grouped by mechanism of action, including lymphocyte trafficking inhibitors, JAK inhibitors, and interleukin (IL)-12/23 and IL-23 antagonists. Odds ratios for treatment versus placebo were calculated separately for each subgroup, and a ratio of odds ratios was then used to assess whether prior TNF exposure modified drug effect. Analyses were conducted on an intention-to-treat basis, restricted to approved dosing when multiple regimens were tested.
Across five trials of lymphocyte trafficking inhibitors including 2,046 patients, efficacy was significantly greater in TNF-naïve patients compared with those who had prior TNF exposure. The odds of achieving clinical remission were nearly doubled in the TNF-naïve group (ratio of odds ratios [ROR], 1.88; 95% CI, 1.02–3.49).
In six trials of JAK inhibitors including 3,015 patients, remission rates were higher among TNF-exposed patients com-pared with TNF-naïve patients (ROR, 0.47; 95% CI, 0.22–1.01).
In six trials of IL-12/23 and IL-23 antagonists, including 3,810 patients, prior TNF exposure did not significantly modify treatment outcomes (ROR, 1.07; 95% CI, 0.64–1.80). Within individual trials, ustekinumab showed a trend toward great-er efficacy in TNF-exposed patients, whereas selective IL-23 antagonists performed similarly regardless of TNF exposure history.
Secondary analyses of endoscopic improvement yielded results consistent with the primary endpoint. Statistical heterogeneity across trials was minimal, and all included studies were rated at low risk of bias.
The investigators noted several limitations. For example, therapies were grouped broadly by mechanism of action, although specific biologic effects could potentially differ within groups. The analysis also could not account for patients who had failed two or more classes of advanced therapy, which may independently reduce the likelihood of response.
Still, Lee and colleagues suggested that the findings deserve a closer look.
“[T]here is significant heterogeneity of treatment efficacy for induction of remission with different advanced therapies in patients with moderate-severe UC based on prior exposure to TNF antagonists,” they concluded. “Future studies on the mechanistic insight for these intriguing observations are warranted.”
The study was supported by the Leona and Harry B. Helmsley Trust, the National Institutes of Health, and the Centers for Disease Control and Prevention. The investigators disclosed relationships with AbbVie, Ferring, Pfizer, and others.
, based on results of a large meta-analysis.
Patients previously treated with TNF antagonists were less likely to respond to lymphocyte trafficking inhibitors but more likely to achieve remission on Janus kinase (JAK) inhibitors, Han Hee Lee, MD, PhD, of the University of California San Diego, and colleagues reported.
“Treatment options for patients with moderate-severe ulcerative colitis have increased in the last decade with the availability of six different classes of medications,” investigators wrote in Clinical Gastroenterology and Hepatology (2024 Dec. doi:10.1016/j.cgh.2024.12.007). “There is wide interindividual variability in response to specific medications, and drivers of this heterogeneity are critical to understand to be able to choose the best therapy for each individual patient.”
To learn more about the impacts of anti-TNF exposure on subsequent advanced therapies, the investigators conducted a systematic review and meta-analysis of 17 phase 2 and 3 trials. The dataset included 8,871 adults with moderate-severe UC.
The primary outcome was induction of clinical remission at 6–14 weeks, most often defined as a Mayo Clinic score of 2 or lower with no subscore greater than 1. Endoscopic improvement, generally defined as a Mayo endoscopic subscore of 0 or 1, was evaluated as a secondary endpoint.
Advanced therapies were grouped by mechanism of action, including lymphocyte trafficking inhibitors, JAK inhibitors, and interleukin (IL)-12/23 and IL-23 antagonists. Odds ratios for treatment versus placebo were calculated separately for each subgroup, and a ratio of odds ratios was then used to assess whether prior TNF exposure modified drug effect. Analyses were conducted on an intention-to-treat basis, restricted to approved dosing when multiple regimens were tested.
Across five trials of lymphocyte trafficking inhibitors including 2,046 patients, efficacy was significantly greater in TNF-naïve patients compared with those who had prior TNF exposure. The odds of achieving clinical remission were nearly doubled in the TNF-naïve group (ratio of odds ratios [ROR], 1.88; 95% CI, 1.02–3.49).
In six trials of JAK inhibitors including 3,015 patients, remission rates were higher among TNF-exposed patients com-pared with TNF-naïve patients (ROR, 0.47; 95% CI, 0.22–1.01).
In six trials of IL-12/23 and IL-23 antagonists, including 3,810 patients, prior TNF exposure did not significantly modify treatment outcomes (ROR, 1.07; 95% CI, 0.64–1.80). Within individual trials, ustekinumab showed a trend toward great-er efficacy in TNF-exposed patients, whereas selective IL-23 antagonists performed similarly regardless of TNF exposure history.
Secondary analyses of endoscopic improvement yielded results consistent with the primary endpoint. Statistical heterogeneity across trials was minimal, and all included studies were rated at low risk of bias.
The investigators noted several limitations. For example, therapies were grouped broadly by mechanism of action, although specific biologic effects could potentially differ within groups. The analysis also could not account for patients who had failed two or more classes of advanced therapy, which may independently reduce the likelihood of response.
Still, Lee and colleagues suggested that the findings deserve a closer look.
“[T]here is significant heterogeneity of treatment efficacy for induction of remission with different advanced therapies in patients with moderate-severe UC based on prior exposure to TNF antagonists,” they concluded. “Future studies on the mechanistic insight for these intriguing observations are warranted.”
The study was supported by the Leona and Harry B. Helmsley Trust, the National Institutes of Health, and the Centers for Disease Control and Prevention. The investigators disclosed relationships with AbbVie, Ferring, Pfizer, and others.
, based on results of a large meta-analysis.
Patients previously treated with TNF antagonists were less likely to respond to lymphocyte trafficking inhibitors but more likely to achieve remission on Janus kinase (JAK) inhibitors, Han Hee Lee, MD, PhD, of the University of California San Diego, and colleagues reported.
“Treatment options for patients with moderate-severe ulcerative colitis have increased in the last decade with the availability of six different classes of medications,” investigators wrote in Clinical Gastroenterology and Hepatology (2024 Dec. doi:10.1016/j.cgh.2024.12.007). “There is wide interindividual variability in response to specific medications, and drivers of this heterogeneity are critical to understand to be able to choose the best therapy for each individual patient.”
To learn more about the impacts of anti-TNF exposure on subsequent advanced therapies, the investigators conducted a systematic review and meta-analysis of 17 phase 2 and 3 trials. The dataset included 8,871 adults with moderate-severe UC.
The primary outcome was induction of clinical remission at 6–14 weeks, most often defined as a Mayo Clinic score of 2 or lower with no subscore greater than 1. Endoscopic improvement, generally defined as a Mayo endoscopic subscore of 0 or 1, was evaluated as a secondary endpoint.
Advanced therapies were grouped by mechanism of action, including lymphocyte trafficking inhibitors, JAK inhibitors, and interleukin (IL)-12/23 and IL-23 antagonists. Odds ratios for treatment versus placebo were calculated separately for each subgroup, and a ratio of odds ratios was then used to assess whether prior TNF exposure modified drug effect. Analyses were conducted on an intention-to-treat basis, restricted to approved dosing when multiple regimens were tested.
Across five trials of lymphocyte trafficking inhibitors including 2,046 patients, efficacy was significantly greater in TNF-naïve patients compared with those who had prior TNF exposure. The odds of achieving clinical remission were nearly doubled in the TNF-naïve group (ratio of odds ratios [ROR], 1.88; 95% CI, 1.02–3.49).
In six trials of JAK inhibitors including 3,015 patients, remission rates were higher among TNF-exposed patients com-pared with TNF-naïve patients (ROR, 0.47; 95% CI, 0.22–1.01).
In six trials of IL-12/23 and IL-23 antagonists, including 3,810 patients, prior TNF exposure did not significantly modify treatment outcomes (ROR, 1.07; 95% CI, 0.64–1.80). Within individual trials, ustekinumab showed a trend toward great-er efficacy in TNF-exposed patients, whereas selective IL-23 antagonists performed similarly regardless of TNF exposure history.
Secondary analyses of endoscopic improvement yielded results consistent with the primary endpoint. Statistical heterogeneity across trials was minimal, and all included studies were rated at low risk of bias.
The investigators noted several limitations. For example, therapies were grouped broadly by mechanism of action, although specific biologic effects could potentially differ within groups. The analysis also could not account for patients who had failed two or more classes of advanced therapy, which may independently reduce the likelihood of response.
Still, Lee and colleagues suggested that the findings deserve a closer look.
“[T]here is significant heterogeneity of treatment efficacy for induction of remission with different advanced therapies in patients with moderate-severe UC based on prior exposure to TNF antagonists,” they concluded. “Future studies on the mechanistic insight for these intriguing observations are warranted.”
The study was supported by the Leona and Harry B. Helmsley Trust, the National Institutes of Health, and the Centers for Disease Control and Prevention. The investigators disclosed relationships with AbbVie, Ferring, Pfizer, and others.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
‘At-Need’ Endoscopy Equal to Standard Surveillance in Barrett’s Patients?
based on results of a randomized controlled trial.
The Barrett’s Oesophagus Surveillance Versus Endoscopy at Need Study (BOSS) showed that surveillance endoscopy did not significantly improve overall survival (OS) or cancer-specific survival, compared with “at-need” endoscopy requested by patients with symptoms, reported Oliver Old, MD, of Gloucestershire Hospitals NHS Foundation Trust, Gloucester, England, and colleagues.
“Surveillance endoscopy at regular intervals is advocated by major gastroenterology societies and practiced in numerous countries worldwide to detect esophageal adenocarcinoma (EAC) early in these high-risk patients,” investigators wrote in Gastroenterology. However, “there are conflicting observational studies on the benefits of Barrett’s esophagus surveillance.”
To address this knowledge gap, Old and colleagues conducted the first randomized study of its kind. The BOSS trial was a multicenter trial conducted at 109 hospitals across the United Kingdom. Adults with an endoscopic and histologic diagnosis of BE were eligible if they were fit for endoscopy and had no history of high-grade dysplasia, esophageal adenocarcinoma, or prior upper gastrointestinal cancer. Patients with low-grade dysplasia were permitted to enroll, consistent with practice guidelines at the time.
A total of 3,453 participants were randomized between 2009 and 2011 to undergo surveillance endoscopy every 2 years or to receive at-need endoscopy triggered only by symptoms. Patients and clinicians were aware of treatment assignment. In the surveillance group, quadrantic biopsies were taken at 2-cm intervals throughout the Barrett’s segment.
The primary endpoint was OS. Secondary outcomes included cancer-specific survival (deaths from any cancer), time to diagnosis of EAC, stage at diagnosis, number of endoscopies performed, and procedure-related adverse events.
Of the 3,453 patients randomized, 1,733 were assigned to surveillance and 1,719 to symptom-driven, at-need endoscopy. Baseline characteristics were similar between groups; the mean age was 63 years, and about 70% were men.
Over the course of the trial, 25% of patients in the surveillance arm, and 9% in the at-need arm, withdrew from the trial back into clinical care, but allowed data collection of their outcomes. After a median of 12.8 years of follow-up, there was no significant difference in overall survival: 333 deaths occurred in the surveillance group (19.2%) and 356 in the at-need group (20.7%; hazard ratio [HR], 0.95; 95% CI, 0.82-1.10). Cancer-specific survival was also similar across groups, with 108 cancer-related deaths in the surveillance arm and 106 in the at-need arm (HR, 1.01; 95% CI, 0.77-1.33).
EAC was diagnosed in 40 patients in the surveillance arm (2.3%) and 31 in the at-need arm (1.8%), a nonsignificant difference (HR, 1.32; 95% CI, 0.82-2.11). Stage at diagnosis did not differ between the two groups.
Endoscopy use was higher in the surveillance arm, with 6,124 procedures compared with 2,424 in the at-need arm. Serious adverse events were rare, reported in 0.5% of surveillance patients and 0.4% of at-need patients, with most related to complications of endoscopy such as bleeding or perforation.
End-of-trial exit endoscopy, offered only to patients in the at-need group (based on data and safety monitoring committee recommendation), detected an additional eight cases of EAC and eight cases of high-grade dysplasia, but these findings were not included in the primary trial analysis.
“These data challenge current clinical practice where surveillance is advocated for all patients with BE,” the investigators wrote. “These results are likely to influence societal guidelines regarding surveillance for nondysplastic BE and inform decision making for individual patients and clinicians.”
The study was supported by the Health Technology Assessment Programme, United Kingdom. The investigators disclosed no conflicts of interest.
Old et al report the results of a herculean effort to randomize patients with Barrett’s esophagus (BE) to either scheduled endoscopy at 2-year intervals or endoscopy “at need.” While the intent was to understand the protective effect of endoscopic surveillance, this goal was frustrated by the extensive use of endoscopy in the at-need arm. All told, 59% of at-need patients underwent endoscopy at a median of 25.7 month intervals (compared to the 24.8-month median interval in the surveillance group).
This degree of endoscopy use in at-need patients complicates interpretation, since, as the authors note, such contamination would likely bias the results to the null. Also, only 26% of randomized at-need patients took advantage of the study-end endoscopy. In this group, an additional eight cancers and nine high-grade dysplasia were noted, raising the specter that undiagnosed important disease was present in the at-need group.
Given these concerns, the BOSS results do not provide compelling evidence to change clinical practice. I continue to recommend endoscopic surveillance to my BE patients. However, the trial provides valuable insight. First, it prospectively confirms the low incidence of esophageal adenocarcinoma in low-risk BE, a rate of 0.23%/patient-year. Second, a lot of endoscopy is probably not better than some endoscopy in BE surveillance, and current trends seen in guidelines toward lengthening intervals in low-risk patients are likely merited. Finally, clinicians and patients may overestimate the utility of surveillance, and a patient-centered approach, acknowledging the uncertainties of the utility of endoscopy and the low risk of progression to cancer, is appropriate.
Nicholas J. Shaheen, MD, MPH, AGAF, is the Bozymski-Heizer Distinguished Professor of Medicine and senior associate dean for Clinical Research at the University of North Carolina School of Medicine, Chapel Hill, N.C. He has no conflicts to report.
Old et al report the results of a herculean effort to randomize patients with Barrett’s esophagus (BE) to either scheduled endoscopy at 2-year intervals or endoscopy “at need.” While the intent was to understand the protective effect of endoscopic surveillance, this goal was frustrated by the extensive use of endoscopy in the at-need arm. All told, 59% of at-need patients underwent endoscopy at a median of 25.7 month intervals (compared to the 24.8-month median interval in the surveillance group).
This degree of endoscopy use in at-need patients complicates interpretation, since, as the authors note, such contamination would likely bias the results to the null. Also, only 26% of randomized at-need patients took advantage of the study-end endoscopy. In this group, an additional eight cancers and nine high-grade dysplasia were noted, raising the specter that undiagnosed important disease was present in the at-need group.
Given these concerns, the BOSS results do not provide compelling evidence to change clinical practice. I continue to recommend endoscopic surveillance to my BE patients. However, the trial provides valuable insight. First, it prospectively confirms the low incidence of esophageal adenocarcinoma in low-risk BE, a rate of 0.23%/patient-year. Second, a lot of endoscopy is probably not better than some endoscopy in BE surveillance, and current trends seen in guidelines toward lengthening intervals in low-risk patients are likely merited. Finally, clinicians and patients may overestimate the utility of surveillance, and a patient-centered approach, acknowledging the uncertainties of the utility of endoscopy and the low risk of progression to cancer, is appropriate.
Nicholas J. Shaheen, MD, MPH, AGAF, is the Bozymski-Heizer Distinguished Professor of Medicine and senior associate dean for Clinical Research at the University of North Carolina School of Medicine, Chapel Hill, N.C. He has no conflicts to report.
Old et al report the results of a herculean effort to randomize patients with Barrett’s esophagus (BE) to either scheduled endoscopy at 2-year intervals or endoscopy “at need.” While the intent was to understand the protective effect of endoscopic surveillance, this goal was frustrated by the extensive use of endoscopy in the at-need arm. All told, 59% of at-need patients underwent endoscopy at a median of 25.7 month intervals (compared to the 24.8-month median interval in the surveillance group).
This degree of endoscopy use in at-need patients complicates interpretation, since, as the authors note, such contamination would likely bias the results to the null. Also, only 26% of randomized at-need patients took advantage of the study-end endoscopy. In this group, an additional eight cancers and nine high-grade dysplasia were noted, raising the specter that undiagnosed important disease was present in the at-need group.
Given these concerns, the BOSS results do not provide compelling evidence to change clinical practice. I continue to recommend endoscopic surveillance to my BE patients. However, the trial provides valuable insight. First, it prospectively confirms the low incidence of esophageal adenocarcinoma in low-risk BE, a rate of 0.23%/patient-year. Second, a lot of endoscopy is probably not better than some endoscopy in BE surveillance, and current trends seen in guidelines toward lengthening intervals in low-risk patients are likely merited. Finally, clinicians and patients may overestimate the utility of surveillance, and a patient-centered approach, acknowledging the uncertainties of the utility of endoscopy and the low risk of progression to cancer, is appropriate.
Nicholas J. Shaheen, MD, MPH, AGAF, is the Bozymski-Heizer Distinguished Professor of Medicine and senior associate dean for Clinical Research at the University of North Carolina School of Medicine, Chapel Hill, N.C. He has no conflicts to report.
based on results of a randomized controlled trial.
The Barrett’s Oesophagus Surveillance Versus Endoscopy at Need Study (BOSS) showed that surveillance endoscopy did not significantly improve overall survival (OS) or cancer-specific survival, compared with “at-need” endoscopy requested by patients with symptoms, reported Oliver Old, MD, of Gloucestershire Hospitals NHS Foundation Trust, Gloucester, England, and colleagues.
“Surveillance endoscopy at regular intervals is advocated by major gastroenterology societies and practiced in numerous countries worldwide to detect esophageal adenocarcinoma (EAC) early in these high-risk patients,” investigators wrote in Gastroenterology. However, “there are conflicting observational studies on the benefits of Barrett’s esophagus surveillance.”
To address this knowledge gap, Old and colleagues conducted the first randomized study of its kind. The BOSS trial was a multicenter trial conducted at 109 hospitals across the United Kingdom. Adults with an endoscopic and histologic diagnosis of BE were eligible if they were fit for endoscopy and had no history of high-grade dysplasia, esophageal adenocarcinoma, or prior upper gastrointestinal cancer. Patients with low-grade dysplasia were permitted to enroll, consistent with practice guidelines at the time.
A total of 3,453 participants were randomized between 2009 and 2011 to undergo surveillance endoscopy every 2 years or to receive at-need endoscopy triggered only by symptoms. Patients and clinicians were aware of treatment assignment. In the surveillance group, quadrantic biopsies were taken at 2-cm intervals throughout the Barrett’s segment.
The primary endpoint was OS. Secondary outcomes included cancer-specific survival (deaths from any cancer), time to diagnosis of EAC, stage at diagnosis, number of endoscopies performed, and procedure-related adverse events.
Of the 3,453 patients randomized, 1,733 were assigned to surveillance and 1,719 to symptom-driven, at-need endoscopy. Baseline characteristics were similar between groups; the mean age was 63 years, and about 70% were men.
Over the course of the trial, 25% of patients in the surveillance arm, and 9% in the at-need arm, withdrew from the trial back into clinical care, but allowed data collection of their outcomes. After a median of 12.8 years of follow-up, there was no significant difference in overall survival: 333 deaths occurred in the surveillance group (19.2%) and 356 in the at-need group (20.7%; hazard ratio [HR], 0.95; 95% CI, 0.82-1.10). Cancer-specific survival was also similar across groups, with 108 cancer-related deaths in the surveillance arm and 106 in the at-need arm (HR, 1.01; 95% CI, 0.77-1.33).
EAC was diagnosed in 40 patients in the surveillance arm (2.3%) and 31 in the at-need arm (1.8%), a nonsignificant difference (HR, 1.32; 95% CI, 0.82-2.11). Stage at diagnosis did not differ between the two groups.
Endoscopy use was higher in the surveillance arm, with 6,124 procedures compared with 2,424 in the at-need arm. Serious adverse events were rare, reported in 0.5% of surveillance patients and 0.4% of at-need patients, with most related to complications of endoscopy such as bleeding or perforation.
End-of-trial exit endoscopy, offered only to patients in the at-need group (based on data and safety monitoring committee recommendation), detected an additional eight cases of EAC and eight cases of high-grade dysplasia, but these findings were not included in the primary trial analysis.
“These data challenge current clinical practice where surveillance is advocated for all patients with BE,” the investigators wrote. “These results are likely to influence societal guidelines regarding surveillance for nondysplastic BE and inform decision making for individual patients and clinicians.”
The study was supported by the Health Technology Assessment Programme, United Kingdom. The investigators disclosed no conflicts of interest.
based on results of a randomized controlled trial.
The Barrett’s Oesophagus Surveillance Versus Endoscopy at Need Study (BOSS) showed that surveillance endoscopy did not significantly improve overall survival (OS) or cancer-specific survival, compared with “at-need” endoscopy requested by patients with symptoms, reported Oliver Old, MD, of Gloucestershire Hospitals NHS Foundation Trust, Gloucester, England, and colleagues.
“Surveillance endoscopy at regular intervals is advocated by major gastroenterology societies and practiced in numerous countries worldwide to detect esophageal adenocarcinoma (EAC) early in these high-risk patients,” investigators wrote in Gastroenterology. However, “there are conflicting observational studies on the benefits of Barrett’s esophagus surveillance.”
To address this knowledge gap, Old and colleagues conducted the first randomized study of its kind. The BOSS trial was a multicenter trial conducted at 109 hospitals across the United Kingdom. Adults with an endoscopic and histologic diagnosis of BE were eligible if they were fit for endoscopy and had no history of high-grade dysplasia, esophageal adenocarcinoma, or prior upper gastrointestinal cancer. Patients with low-grade dysplasia were permitted to enroll, consistent with practice guidelines at the time.
A total of 3,453 participants were randomized between 2009 and 2011 to undergo surveillance endoscopy every 2 years or to receive at-need endoscopy triggered only by symptoms. Patients and clinicians were aware of treatment assignment. In the surveillance group, quadrantic biopsies were taken at 2-cm intervals throughout the Barrett’s segment.
The primary endpoint was OS. Secondary outcomes included cancer-specific survival (deaths from any cancer), time to diagnosis of EAC, stage at diagnosis, number of endoscopies performed, and procedure-related adverse events.
Of the 3,453 patients randomized, 1,733 were assigned to surveillance and 1,719 to symptom-driven, at-need endoscopy. Baseline characteristics were similar between groups; the mean age was 63 years, and about 70% were men.
Over the course of the trial, 25% of patients in the surveillance arm, and 9% in the at-need arm, withdrew from the trial back into clinical care, but allowed data collection of their outcomes. After a median of 12.8 years of follow-up, there was no significant difference in overall survival: 333 deaths occurred in the surveillance group (19.2%) and 356 in the at-need group (20.7%; hazard ratio [HR], 0.95; 95% CI, 0.82-1.10). Cancer-specific survival was also similar across groups, with 108 cancer-related deaths in the surveillance arm and 106 in the at-need arm (HR, 1.01; 95% CI, 0.77-1.33).
EAC was diagnosed in 40 patients in the surveillance arm (2.3%) and 31 in the at-need arm (1.8%), a nonsignificant difference (HR, 1.32; 95% CI, 0.82-2.11). Stage at diagnosis did not differ between the two groups.
Endoscopy use was higher in the surveillance arm, with 6,124 procedures compared with 2,424 in the at-need arm. Serious adverse events were rare, reported in 0.5% of surveillance patients and 0.4% of at-need patients, with most related to complications of endoscopy such as bleeding or perforation.
End-of-trial exit endoscopy, offered only to patients in the at-need group (based on data and safety monitoring committee recommendation), detected an additional eight cases of EAC and eight cases of high-grade dysplasia, but these findings were not included in the primary trial analysis.
“These data challenge current clinical practice where surveillance is advocated for all patients with BE,” the investigators wrote. “These results are likely to influence societal guidelines regarding surveillance for nondysplastic BE and inform decision making for individual patients and clinicians.”
The study was supported by the Health Technology Assessment Programme, United Kingdom. The investigators disclosed no conflicts of interest.
FROM GASTROENTEROLOGY
MASLD/MASH Global Consensus Recommendations Address Guideline Discordance
These recommendations aim to boost guideline adherence and disease awareness, which have lagged despite a surge of national and international guidance in recent years, lead author Zobair M. Younossi, MD, of the Global NASH/MASH Council, Washington, DC, and colleagues, reported.
“Although these documents are similar in many ways, there are important differences in their recommendations, which have created some confusion within the field,” the panel wrote in Gastroenterology. “Areas of discordance among guidelines can be partly responsible for their low rate of implementation and the suboptimal awareness about this liver disease. Furthermore, these guidelines can be long and complex, making it challenging for busy clinicians to access the appropriate information quickly and efficiently.”
To address these gaps, more than 40 experts from around the world collaborated on the consensus project. The team reviewed 61 eligible documents published between 2018 and January 2025. Each guideline was evaluated across eight domains: epidemiology; screening; risk stratification using noninvasive tests (NITs); lifestyle management; treatment with existing medications; treatment with future medications; hepatocellular carcinoma (HCC) and preventive guidance; and pregnancy and pediatric populations.
Areas of discordance were advanced to a Delphi process using iterative online surveys, with a supermajority threshold of 67% required for acceptance. Four Delphi rounds were conducted, and by the end, all statements had achieved more than 90% agreement. The final recommendations were then summarized into practical algorithms for clinical use.
The results cover the full spectrum of MASLD care. For screening and diagnosis, experts agreed that individuals with type 2 diabetes, obesity plus cardiometabolic risk factors, or persistently elevated aminotransferases should be considered high risk. Alcohol thresholds were standardized, clarifying when to classify disease as MASLD, alcohol-related liver disease, or the hybrid “Met-ALD.”
For risk stratification, the panel endorsed a two-step algorithm beginning with the Fibrosis-4 (FIB-4) index, followed by vibration-controlled transient elastography (VCTE) or other NITs in patients above the threshold. This approach, the authors noted, was designed to be feasible in both primary care and specialty settings.
Lifestyle intervention remains the cornerstone of treatment, with weight-loss goals of 5% to reduce steatosis, 7%–10% to reduce inflammation, and at least 10% to improve fibrosis. To this end, the panel recommended a Mediterranean-style diet, increased physical activity, and reductions in sedentary time.
Drug therapy recommendations prioritized glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors for patients with diabetes or obesity, though these were not considered MASH-specific agents. Pioglitazone was noted as an option for diabetes management but not as direct MASH therapy. The panel did not recommend vitamin E, ursodeoxycholic acid, or omega-3 fatty acids, citing insufficient evidence.
The document also provides structured guidance on resmetirom, the first FDA-approved therapy for MASH. Its use was endorsed in patients with F2–F3 fibrosis confirmed by NITs, with safety checks at 3, 6, and 12 months, and efficacy evaluation after 1 year. Treatment futility was defined as concordant worsening across two NITs.
Preventive recommendations included hepatitis A and B vaccination and HCC surveillance every 6 months in patients with cirrhosis. Surveillance in noncirrhotic MASH was left to clinician judgment, based on individualized risk factors. Special considerations were outlined for pediatric and pregnant populations, although the evidence base in these groups remains sparse.
“Further research is required to determine the effectiveness of this algorithm in raising awareness of MASLD and its treatment,” Dr. Younossi and colleagues concluded.
The study was supported by the Global NASH/MASH Council, Inova Health System, and an unrestricted educational grant from Madrigal Pharmaceuticals. The investigators disclosed relationships with Sanofi, Gilead, AstraZeneca, and others.
The new consensus MASLD recommendations should help reconcile the “important differences” between guidelines from around the world, said Dr. Jaideep Behari, of the the University of Pittsburgh Medical Center.
Behari highlighted several points that may be underappreciated in clinical practice. “While many clinicians associate MASLD with obesity and type 2 diabetes, approximately a fifth of people living with MASLD are lean,” he said. “It may also come as a surprise to non-liver specialists that cardiovascular disease is the most common cause of mortality in patients with MASLD.”
He underscored the consensus recommendation to screen patients with type 2 diabetes, those with obesity and at least one cardiometabolic risk factor, and individuals with persistently elevated liver enzymes.
“Since many patients in the first two groups are mainly seen in primary care or endocrinology practices, physicians in these specialties need to be cognizant of these global consensus recommendations,” Behari said.
Turning to therapeutics, he described resmetirom as “a major milestone in the management of MASLD since it is the first drug approved in the US for treatment of MASH with F2 (moderate) or F3 (advanced) fibrosis.”
He noted that treatment requires careful patient selection and monitoring, including VCTE in the 8–20 kPa range, followed by serial liver injury testing. Efficacy should be assessed at 12 months, he noted, since “resmetirom was found to be effective in approximately a quarter of all treated patients in the pivotal clinical trial.”
“These limitations highlight the gaps in the treatment of MASLD/MASH and the need to continue development of other therapies,” Behari said.
Jaideep Behari, MD, PhD, AGAF, is director of the liver steatosis and metabolic wellness program at the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. He reported research grant support from AstraZeneca, Madrigal, and recently completed research grant support from Gilead and Pfizer.
The new consensus MASLD recommendations should help reconcile the “important differences” between guidelines from around the world, said Dr. Jaideep Behari, of the the University of Pittsburgh Medical Center.
Behari highlighted several points that may be underappreciated in clinical practice. “While many clinicians associate MASLD with obesity and type 2 diabetes, approximately a fifth of people living with MASLD are lean,” he said. “It may also come as a surprise to non-liver specialists that cardiovascular disease is the most common cause of mortality in patients with MASLD.”
He underscored the consensus recommendation to screen patients with type 2 diabetes, those with obesity and at least one cardiometabolic risk factor, and individuals with persistently elevated liver enzymes.
“Since many patients in the first two groups are mainly seen in primary care or endocrinology practices, physicians in these specialties need to be cognizant of these global consensus recommendations,” Behari said.
Turning to therapeutics, he described resmetirom as “a major milestone in the management of MASLD since it is the first drug approved in the US for treatment of MASH with F2 (moderate) or F3 (advanced) fibrosis.”
He noted that treatment requires careful patient selection and monitoring, including VCTE in the 8–20 kPa range, followed by serial liver injury testing. Efficacy should be assessed at 12 months, he noted, since “resmetirom was found to be effective in approximately a quarter of all treated patients in the pivotal clinical trial.”
“These limitations highlight the gaps in the treatment of MASLD/MASH and the need to continue development of other therapies,” Behari said.
Jaideep Behari, MD, PhD, AGAF, is director of the liver steatosis and metabolic wellness program at the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. He reported research grant support from AstraZeneca, Madrigal, and recently completed research grant support from Gilead and Pfizer.
The new consensus MASLD recommendations should help reconcile the “important differences” between guidelines from around the world, said Dr. Jaideep Behari, of the the University of Pittsburgh Medical Center.
Behari highlighted several points that may be underappreciated in clinical practice. “While many clinicians associate MASLD with obesity and type 2 diabetes, approximately a fifth of people living with MASLD are lean,” he said. “It may also come as a surprise to non-liver specialists that cardiovascular disease is the most common cause of mortality in patients with MASLD.”
He underscored the consensus recommendation to screen patients with type 2 diabetes, those with obesity and at least one cardiometabolic risk factor, and individuals with persistently elevated liver enzymes.
“Since many patients in the first two groups are mainly seen in primary care or endocrinology practices, physicians in these specialties need to be cognizant of these global consensus recommendations,” Behari said.
Turning to therapeutics, he described resmetirom as “a major milestone in the management of MASLD since it is the first drug approved in the US for treatment of MASH with F2 (moderate) or F3 (advanced) fibrosis.”
He noted that treatment requires careful patient selection and monitoring, including VCTE in the 8–20 kPa range, followed by serial liver injury testing. Efficacy should be assessed at 12 months, he noted, since “resmetirom was found to be effective in approximately a quarter of all treated patients in the pivotal clinical trial.”
“These limitations highlight the gaps in the treatment of MASLD/MASH and the need to continue development of other therapies,” Behari said.
Jaideep Behari, MD, PhD, AGAF, is director of the liver steatosis and metabolic wellness program at the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. He reported research grant support from AstraZeneca, Madrigal, and recently completed research grant support from Gilead and Pfizer.
These recommendations aim to boost guideline adherence and disease awareness, which have lagged despite a surge of national and international guidance in recent years, lead author Zobair M. Younossi, MD, of the Global NASH/MASH Council, Washington, DC, and colleagues, reported.
“Although these documents are similar in many ways, there are important differences in their recommendations, which have created some confusion within the field,” the panel wrote in Gastroenterology. “Areas of discordance among guidelines can be partly responsible for their low rate of implementation and the suboptimal awareness about this liver disease. Furthermore, these guidelines can be long and complex, making it challenging for busy clinicians to access the appropriate information quickly and efficiently.”
To address these gaps, more than 40 experts from around the world collaborated on the consensus project. The team reviewed 61 eligible documents published between 2018 and January 2025. Each guideline was evaluated across eight domains: epidemiology; screening; risk stratification using noninvasive tests (NITs); lifestyle management; treatment with existing medications; treatment with future medications; hepatocellular carcinoma (HCC) and preventive guidance; and pregnancy and pediatric populations.
Areas of discordance were advanced to a Delphi process using iterative online surveys, with a supermajority threshold of 67% required for acceptance. Four Delphi rounds were conducted, and by the end, all statements had achieved more than 90% agreement. The final recommendations were then summarized into practical algorithms for clinical use.
The results cover the full spectrum of MASLD care. For screening and diagnosis, experts agreed that individuals with type 2 diabetes, obesity plus cardiometabolic risk factors, or persistently elevated aminotransferases should be considered high risk. Alcohol thresholds were standardized, clarifying when to classify disease as MASLD, alcohol-related liver disease, or the hybrid “Met-ALD.”
For risk stratification, the panel endorsed a two-step algorithm beginning with the Fibrosis-4 (FIB-4) index, followed by vibration-controlled transient elastography (VCTE) or other NITs in patients above the threshold. This approach, the authors noted, was designed to be feasible in both primary care and specialty settings.
Lifestyle intervention remains the cornerstone of treatment, with weight-loss goals of 5% to reduce steatosis, 7%–10% to reduce inflammation, and at least 10% to improve fibrosis. To this end, the panel recommended a Mediterranean-style diet, increased physical activity, and reductions in sedentary time.
Drug therapy recommendations prioritized glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors for patients with diabetes or obesity, though these were not considered MASH-specific agents. Pioglitazone was noted as an option for diabetes management but not as direct MASH therapy. The panel did not recommend vitamin E, ursodeoxycholic acid, or omega-3 fatty acids, citing insufficient evidence.
The document also provides structured guidance on resmetirom, the first FDA-approved therapy for MASH. Its use was endorsed in patients with F2–F3 fibrosis confirmed by NITs, with safety checks at 3, 6, and 12 months, and efficacy evaluation after 1 year. Treatment futility was defined as concordant worsening across two NITs.
Preventive recommendations included hepatitis A and B vaccination and HCC surveillance every 6 months in patients with cirrhosis. Surveillance in noncirrhotic MASH was left to clinician judgment, based on individualized risk factors. Special considerations were outlined for pediatric and pregnant populations, although the evidence base in these groups remains sparse.
“Further research is required to determine the effectiveness of this algorithm in raising awareness of MASLD and its treatment,” Dr. Younossi and colleagues concluded.
The study was supported by the Global NASH/MASH Council, Inova Health System, and an unrestricted educational grant from Madrigal Pharmaceuticals. The investigators disclosed relationships with Sanofi, Gilead, AstraZeneca, and others.
These recommendations aim to boost guideline adherence and disease awareness, which have lagged despite a surge of national and international guidance in recent years, lead author Zobair M. Younossi, MD, of the Global NASH/MASH Council, Washington, DC, and colleagues, reported.
“Although these documents are similar in many ways, there are important differences in their recommendations, which have created some confusion within the field,” the panel wrote in Gastroenterology. “Areas of discordance among guidelines can be partly responsible for their low rate of implementation and the suboptimal awareness about this liver disease. Furthermore, these guidelines can be long and complex, making it challenging for busy clinicians to access the appropriate information quickly and efficiently.”
To address these gaps, more than 40 experts from around the world collaborated on the consensus project. The team reviewed 61 eligible documents published between 2018 and January 2025. Each guideline was evaluated across eight domains: epidemiology; screening; risk stratification using noninvasive tests (NITs); lifestyle management; treatment with existing medications; treatment with future medications; hepatocellular carcinoma (HCC) and preventive guidance; and pregnancy and pediatric populations.
Areas of discordance were advanced to a Delphi process using iterative online surveys, with a supermajority threshold of 67% required for acceptance. Four Delphi rounds were conducted, and by the end, all statements had achieved more than 90% agreement. The final recommendations were then summarized into practical algorithms for clinical use.
The results cover the full spectrum of MASLD care. For screening and diagnosis, experts agreed that individuals with type 2 diabetes, obesity plus cardiometabolic risk factors, or persistently elevated aminotransferases should be considered high risk. Alcohol thresholds were standardized, clarifying when to classify disease as MASLD, alcohol-related liver disease, or the hybrid “Met-ALD.”
For risk stratification, the panel endorsed a two-step algorithm beginning with the Fibrosis-4 (FIB-4) index, followed by vibration-controlled transient elastography (VCTE) or other NITs in patients above the threshold. This approach, the authors noted, was designed to be feasible in both primary care and specialty settings.
Lifestyle intervention remains the cornerstone of treatment, with weight-loss goals of 5% to reduce steatosis, 7%–10% to reduce inflammation, and at least 10% to improve fibrosis. To this end, the panel recommended a Mediterranean-style diet, increased physical activity, and reductions in sedentary time.
Drug therapy recommendations prioritized glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors for patients with diabetes or obesity, though these were not considered MASH-specific agents. Pioglitazone was noted as an option for diabetes management but not as direct MASH therapy. The panel did not recommend vitamin E, ursodeoxycholic acid, or omega-3 fatty acids, citing insufficient evidence.
The document also provides structured guidance on resmetirom, the first FDA-approved therapy for MASH. Its use was endorsed in patients with F2–F3 fibrosis confirmed by NITs, with safety checks at 3, 6, and 12 months, and efficacy evaluation after 1 year. Treatment futility was defined as concordant worsening across two NITs.
Preventive recommendations included hepatitis A and B vaccination and HCC surveillance every 6 months in patients with cirrhosis. Surveillance in noncirrhotic MASH was left to clinician judgment, based on individualized risk factors. Special considerations were outlined for pediatric and pregnant populations, although the evidence base in these groups remains sparse.
“Further research is required to determine the effectiveness of this algorithm in raising awareness of MASLD and its treatment,” Dr. Younossi and colleagues concluded.
The study was supported by the Global NASH/MASH Council, Inova Health System, and an unrestricted educational grant from Madrigal Pharmaceuticals. The investigators disclosed relationships with Sanofi, Gilead, AstraZeneca, and others.
FROM GASTROENTEROLOGY
Long-Term Data Support Reduced-Dose Maintenance in EoE
, according to a recent meta-analysis of long-term data.
These findings support keeping patients on long-term maintenance therapy to prevent relapse, lead author Alberto Barchi, MD, of IRCCS Ospedale San Raffaele, Milan, Italy, and colleagues, reported.
“Given the high relapse rate after treatment cessation, despite good initial response after induction, there is need for further information about long-term outcomes of maintenance treatments,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, few studies have focused on long-term effects of EoE therapies.”
In response, Dr. Barchi and colleagues conducted the present systematic review and meta-analysis, which included studies evaluating maintenance therapies for EoE with at least 48 weeks of follow-up. Eligible studies enrolled patients with confirmed EoE who had received an induction regimen and continued therapy long-term. The final dataset comprised 9 randomized controlled trials (RCTs) and 11 observational studies, with long-term outcomes were reported among 1,819 patients.
The primary outcome was histologic success, defined as fewer than 15 or 6 eosinophils per high-power field (HPF). Secondary outcomes included clinical and endoscopic response, treatment adherence, and safety events.
Random-effects meta-analyses were performed, with randomized trials and observational studies analyzed separately. Risk ratios for sustained remission versus placebo or induction therapy were calculated, and heterogeneity was assessed using the I² statistic. Safety outcomes included pooled rates of adverse events, severe adverse events, and treatment discontinuation.
Across 9 randomized controlled trials, swallowed topical corticosteroids (STCs) maintained histologic remission (less than 15 eosinophils/HPF) in 86% of patients, while biologics achieved a rate of 79%. At the stricter threshold of less than 6 eosinophils/HPF, remission rates for STCs and biologics were 59% and 70%, respectively.
Clinical remission rates were lower, at 58% for STCs and 59% for biologics. Endoscopic outcomes were less consistent-ly reported, but most trials showed stable or improved scores during long-term treatment.
In observational cohorts, proton pump inhibitors (PPIs) maintained histologic remission in 64% of patients and clinical remission in 80%. For STCs in the real-world setting, histologic and clinical remission rates were 49% and 51%, respectively.
Stepping down the dose of maintenance therapy—whether conventional or biologic—did not increase relapse risk (RR 1.04; 95% CI, 0.72–1.51). In contrast, treatment withdrawal was clearly associated with higher relapse rates: in pooled analyses, continuing therapy yielded nearly an 8-fold greater likelihood of sustained remission compared with discontinuation (RR 7.87; 95% CI, 4.19–14.77).
Safety signals were favorable. Severe adverse events occurred in 3% of patients in randomized trials and 5% in observational studies, while overall withdrawal rates were 10% and 4%, respectively. The most common adverse events with STCs were oropharyngeal candidiasis and reductions in morning cortisol, while biologics were mainly associated with injection-site reactions, headache, and nasopharyngitis.
“Results suggest that prolonging treatment is efficient in maintaining histologic and clinical remission, with overall drug-related safe profiles both in randomized trials and observational studies,” the investigators concluded, noting that more work is needed to determine if there is an optimal drug for maintenance therapy, and if certain patients can successfully discontinue treatment.
The investigators disclosed relationships with Pfizer, UCB Pharma, AstraZeneca, and others.
, according to a recent meta-analysis of long-term data.
These findings support keeping patients on long-term maintenance therapy to prevent relapse, lead author Alberto Barchi, MD, of IRCCS Ospedale San Raffaele, Milan, Italy, and colleagues, reported.
“Given the high relapse rate after treatment cessation, despite good initial response after induction, there is need for further information about long-term outcomes of maintenance treatments,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, few studies have focused on long-term effects of EoE therapies.”
In response, Dr. Barchi and colleagues conducted the present systematic review and meta-analysis, which included studies evaluating maintenance therapies for EoE with at least 48 weeks of follow-up. Eligible studies enrolled patients with confirmed EoE who had received an induction regimen and continued therapy long-term. The final dataset comprised 9 randomized controlled trials (RCTs) and 11 observational studies, with long-term outcomes were reported among 1,819 patients.
The primary outcome was histologic success, defined as fewer than 15 or 6 eosinophils per high-power field (HPF). Secondary outcomes included clinical and endoscopic response, treatment adherence, and safety events.
Random-effects meta-analyses were performed, with randomized trials and observational studies analyzed separately. Risk ratios for sustained remission versus placebo or induction therapy were calculated, and heterogeneity was assessed using the I² statistic. Safety outcomes included pooled rates of adverse events, severe adverse events, and treatment discontinuation.
Across 9 randomized controlled trials, swallowed topical corticosteroids (STCs) maintained histologic remission (less than 15 eosinophils/HPF) in 86% of patients, while biologics achieved a rate of 79%. At the stricter threshold of less than 6 eosinophils/HPF, remission rates for STCs and biologics were 59% and 70%, respectively.
Clinical remission rates were lower, at 58% for STCs and 59% for biologics. Endoscopic outcomes were less consistent-ly reported, but most trials showed stable or improved scores during long-term treatment.
In observational cohorts, proton pump inhibitors (PPIs) maintained histologic remission in 64% of patients and clinical remission in 80%. For STCs in the real-world setting, histologic and clinical remission rates were 49% and 51%, respectively.
Stepping down the dose of maintenance therapy—whether conventional or biologic—did not increase relapse risk (RR 1.04; 95% CI, 0.72–1.51). In contrast, treatment withdrawal was clearly associated with higher relapse rates: in pooled analyses, continuing therapy yielded nearly an 8-fold greater likelihood of sustained remission compared with discontinuation (RR 7.87; 95% CI, 4.19–14.77).
Safety signals were favorable. Severe adverse events occurred in 3% of patients in randomized trials and 5% in observational studies, while overall withdrawal rates were 10% and 4%, respectively. The most common adverse events with STCs were oropharyngeal candidiasis and reductions in morning cortisol, while biologics were mainly associated with injection-site reactions, headache, and nasopharyngitis.
“Results suggest that prolonging treatment is efficient in maintaining histologic and clinical remission, with overall drug-related safe profiles both in randomized trials and observational studies,” the investigators concluded, noting that more work is needed to determine if there is an optimal drug for maintenance therapy, and if certain patients can successfully discontinue treatment.
The investigators disclosed relationships with Pfizer, UCB Pharma, AstraZeneca, and others.
, according to a recent meta-analysis of long-term data.
These findings support keeping patients on long-term maintenance therapy to prevent relapse, lead author Alberto Barchi, MD, of IRCCS Ospedale San Raffaele, Milan, Italy, and colleagues, reported.
“Given the high relapse rate after treatment cessation, despite good initial response after induction, there is need for further information about long-term outcomes of maintenance treatments,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, few studies have focused on long-term effects of EoE therapies.”
In response, Dr. Barchi and colleagues conducted the present systematic review and meta-analysis, which included studies evaluating maintenance therapies for EoE with at least 48 weeks of follow-up. Eligible studies enrolled patients with confirmed EoE who had received an induction regimen and continued therapy long-term. The final dataset comprised 9 randomized controlled trials (RCTs) and 11 observational studies, with long-term outcomes were reported among 1,819 patients.
The primary outcome was histologic success, defined as fewer than 15 or 6 eosinophils per high-power field (HPF). Secondary outcomes included clinical and endoscopic response, treatment adherence, and safety events.
Random-effects meta-analyses were performed, with randomized trials and observational studies analyzed separately. Risk ratios for sustained remission versus placebo or induction therapy were calculated, and heterogeneity was assessed using the I² statistic. Safety outcomes included pooled rates of adverse events, severe adverse events, and treatment discontinuation.
Across 9 randomized controlled trials, swallowed topical corticosteroids (STCs) maintained histologic remission (less than 15 eosinophils/HPF) in 86% of patients, while biologics achieved a rate of 79%. At the stricter threshold of less than 6 eosinophils/HPF, remission rates for STCs and biologics were 59% and 70%, respectively.
Clinical remission rates were lower, at 58% for STCs and 59% for biologics. Endoscopic outcomes were less consistent-ly reported, but most trials showed stable or improved scores during long-term treatment.
In observational cohorts, proton pump inhibitors (PPIs) maintained histologic remission in 64% of patients and clinical remission in 80%. For STCs in the real-world setting, histologic and clinical remission rates were 49% and 51%, respectively.
Stepping down the dose of maintenance therapy—whether conventional or biologic—did not increase relapse risk (RR 1.04; 95% CI, 0.72–1.51). In contrast, treatment withdrawal was clearly associated with higher relapse rates: in pooled analyses, continuing therapy yielded nearly an 8-fold greater likelihood of sustained remission compared with discontinuation (RR 7.87; 95% CI, 4.19–14.77).
Safety signals were favorable. Severe adverse events occurred in 3% of patients in randomized trials and 5% in observational studies, while overall withdrawal rates were 10% and 4%, respectively. The most common adverse events with STCs were oropharyngeal candidiasis and reductions in morning cortisol, while biologics were mainly associated with injection-site reactions, headache, and nasopharyngitis.
“Results suggest that prolonging treatment is efficient in maintaining histologic and clinical remission, with overall drug-related safe profiles both in randomized trials and observational studies,” the investigators concluded, noting that more work is needed to determine if there is an optimal drug for maintenance therapy, and if certain patients can successfully discontinue treatment.
The investigators disclosed relationships with Pfizer, UCB Pharma, AstraZeneca, and others.
FROM GASTROENTEROLOGY
Simpler Approach Increases Diagnostic Accuracy of Timed Barium Esophagram for Achalasia
, according to investigators.
The classification tree offers a practical alternative for evaluating esophagogastric junction (EGJ) outflow disorders when more advanced methods like high-resolution manometry (HRM) or functional lumen imaging probe (FLIP) panometry are unavailable, lead author Ofer Z. Fass, MD, of Northwestern University, Chicago, and colleagues reported.
“[T]here are limited data on normative TBE values,” the investigators wrote in Gastroenterology. “Furthermore, data supporting the accuracy of TBE as a screening test for esophageal motility disorders, as well as clinically relevant test thresholds, remains limited.”
TBE is conventionally interpreted using a handful of single measurements, most often the barium column height at 1, 2, or 5 minutes. Although these metrics are simple to obtain, variability in technique, cutoff values, and interpretation across centers limits reproducibility and weakens diagnostic accuracy, according to the investigators. The role of TBE has therefore been largely confined to adjudicating inconclusive manometry findings, but even in that setting, the absence of validated reference standards constrains its utility as a reliable screening tool.
To address this gap, Fass and colleagues conducted a prospective analysis of 290 patients who underwent TBE at Northwestern Memorial Hospital, Chicago, with HRM and FLIP panometry, interpreted according to the Chicago Classification version 4.0 (CCv4.0), serving as the diagnostic reference standards.
Patients were included if they had both TBE and manometry performed within a short interval, ensuring that the two tests could be meaningfully compared. The study population represented a broad spectrum of esophageal motility presentations, allowing the model to be trained on clinically relevant variation.
Beyond column height, the investigators measured barium height at multiple timepoints, maximal esophageal body width, maximum EGJ diameter, and tablet passage. These variables were incorporated into a recursive partitioning algorithm to build a multimetric classification tree aimed at distinguishing EGJ outflow obstruction from other motility disorders.
The optimal tree incorporated three sequential decision levels. At the top was maximum esophageal body width, followed by EGJ diameter and barium height at the second level, and tablet passage at the third. This stepwise structure allowed the model to refine diagnoses by combining simple, reproducible TBE metrics that are already collected in routine practice.
Among the 290 patients, 121 (42%) had EGJ outflow disorders, 151 (52%) had no outflow disorder, and 18 (6%) had inconclusive manometry findings. Using conventional interpretation with column height and tablet passage, TBE demonstrated a sensitivity of 77.8%, a specificity of 86.0%, and an accuracy of 82.2%. The multimetric classification tree improved diagnostic performance across all parameters, with a sensitivity of 84.2%, a specificity of 92.1%, and an accuracy of 88.3%.
The advantages of multimetric interpretation were most notable in patients with borderline column heights, which single-metric approaches often misclassify, underscoring the value of integrating multiple measurements into a unified model.
“[T]his study demonstrated that TBE can accurately identify achalasia when analyzed using multiple metrics in a classification tree model,” Fass and colleagues wrote. “Future studies should explore the use of TBE metrics and models to identify more specific esophageal motor disorders (such as esophageal spasm and absent contractility), as well as validation in a larger, multicenter cohort.”
Clinical Takeaways
Rishi Naik, MD, of the Center for Swallowing and Esophageal Disorders, Vanderbilt University Medical Center, Nashville, Tennessee, said the study represents a step forward in how clinicians can use a widely accessible esophageal imaging test.
“This study is important in that it has updated the way we use a very common, readily available imaging test and compared it to the current gold standard of HRM and FLIP,” he told GI & Hepatology News. “This provides a practical, standardized framework for clinicians evaluating patients with suspected esophageal motility disorders.”
Naik noted that while HRM and FLIP provide highly detailed information, both carry drawbacks that limit their universal adoption.
“Practically, HRM is a transnasal test that can be cumbersome, and FLIP is performed during a sedated procedure,” he said. “From a comfort and cost perspective, the esophagram outcompetes. What the TBE lacked was adequate sensitivity and specificity when just looking at column height, which is how the authors overcame this by leveraging the comparisons using CCv4.0.”
Implementation, however, requires discipline.
“A timed barium esophagram is a protocol, not a single esophagram,” Naik said. “Without proper measurements, you can’t follow the decision tree.”
Still, he pointed to radiology’s increasing adoption of artificial intelligence (AI) as a promising way forward.
“AI has already transformed radiological reads, and I’m optimistic it will eventually allow us to incorporate not only width, height, and tablet clearance but also 3D [three-dimensional] reconstructions of bolus retention and pressure to enhance predictive modeling,” Naik said.
This study was supported by the Public Health Service.
The investigators disclosed having relationships with Takeda, Phathom Pharmaceuticals, Medtronic, and others. Naik is a consultant for Sanofi/Regeneron, Eli Lilly and Company, and Renexxion.
A version of this article appeared on Medscape.com.
, according to investigators.
The classification tree offers a practical alternative for evaluating esophagogastric junction (EGJ) outflow disorders when more advanced methods like high-resolution manometry (HRM) or functional lumen imaging probe (FLIP) panometry are unavailable, lead author Ofer Z. Fass, MD, of Northwestern University, Chicago, and colleagues reported.
“[T]here are limited data on normative TBE values,” the investigators wrote in Gastroenterology. “Furthermore, data supporting the accuracy of TBE as a screening test for esophageal motility disorders, as well as clinically relevant test thresholds, remains limited.”
TBE is conventionally interpreted using a handful of single measurements, most often the barium column height at 1, 2, or 5 minutes. Although these metrics are simple to obtain, variability in technique, cutoff values, and interpretation across centers limits reproducibility and weakens diagnostic accuracy, according to the investigators. The role of TBE has therefore been largely confined to adjudicating inconclusive manometry findings, but even in that setting, the absence of validated reference standards constrains its utility as a reliable screening tool.
To address this gap, Fass and colleagues conducted a prospective analysis of 290 patients who underwent TBE at Northwestern Memorial Hospital, Chicago, with HRM and FLIP panometry, interpreted according to the Chicago Classification version 4.0 (CCv4.0), serving as the diagnostic reference standards.
Patients were included if they had both TBE and manometry performed within a short interval, ensuring that the two tests could be meaningfully compared. The study population represented a broad spectrum of esophageal motility presentations, allowing the model to be trained on clinically relevant variation.
Beyond column height, the investigators measured barium height at multiple timepoints, maximal esophageal body width, maximum EGJ diameter, and tablet passage. These variables were incorporated into a recursive partitioning algorithm to build a multimetric classification tree aimed at distinguishing EGJ outflow obstruction from other motility disorders.
The optimal tree incorporated three sequential decision levels. At the top was maximum esophageal body width, followed by EGJ diameter and barium height at the second level, and tablet passage at the third. This stepwise structure allowed the model to refine diagnoses by combining simple, reproducible TBE metrics that are already collected in routine practice.
Among the 290 patients, 121 (42%) had EGJ outflow disorders, 151 (52%) had no outflow disorder, and 18 (6%) had inconclusive manometry findings. Using conventional interpretation with column height and tablet passage, TBE demonstrated a sensitivity of 77.8%, a specificity of 86.0%, and an accuracy of 82.2%. The multimetric classification tree improved diagnostic performance across all parameters, with a sensitivity of 84.2%, a specificity of 92.1%, and an accuracy of 88.3%.
The advantages of multimetric interpretation were most notable in patients with borderline column heights, which single-metric approaches often misclassify, underscoring the value of integrating multiple measurements into a unified model.
“[T]his study demonstrated that TBE can accurately identify achalasia when analyzed using multiple metrics in a classification tree model,” Fass and colleagues wrote. “Future studies should explore the use of TBE metrics and models to identify more specific esophageal motor disorders (such as esophageal spasm and absent contractility), as well as validation in a larger, multicenter cohort.”
Clinical Takeaways
Rishi Naik, MD, of the Center for Swallowing and Esophageal Disorders, Vanderbilt University Medical Center, Nashville, Tennessee, said the study represents a step forward in how clinicians can use a widely accessible esophageal imaging test.
“This study is important in that it has updated the way we use a very common, readily available imaging test and compared it to the current gold standard of HRM and FLIP,” he told GI & Hepatology News. “This provides a practical, standardized framework for clinicians evaluating patients with suspected esophageal motility disorders.”
Naik noted that while HRM and FLIP provide highly detailed information, both carry drawbacks that limit their universal adoption.
“Practically, HRM is a transnasal test that can be cumbersome, and FLIP is performed during a sedated procedure,” he said. “From a comfort and cost perspective, the esophagram outcompetes. What the TBE lacked was adequate sensitivity and specificity when just looking at column height, which is how the authors overcame this by leveraging the comparisons using CCv4.0.”
Implementation, however, requires discipline.
“A timed barium esophagram is a protocol, not a single esophagram,” Naik said. “Without proper measurements, you can’t follow the decision tree.”
Still, he pointed to radiology’s increasing adoption of artificial intelligence (AI) as a promising way forward.
“AI has already transformed radiological reads, and I’m optimistic it will eventually allow us to incorporate not only width, height, and tablet clearance but also 3D [three-dimensional] reconstructions of bolus retention and pressure to enhance predictive modeling,” Naik said.
This study was supported by the Public Health Service.
The investigators disclosed having relationships with Takeda, Phathom Pharmaceuticals, Medtronic, and others. Naik is a consultant for Sanofi/Regeneron, Eli Lilly and Company, and Renexxion.
A version of this article appeared on Medscape.com.
, according to investigators.
The classification tree offers a practical alternative for evaluating esophagogastric junction (EGJ) outflow disorders when more advanced methods like high-resolution manometry (HRM) or functional lumen imaging probe (FLIP) panometry are unavailable, lead author Ofer Z. Fass, MD, of Northwestern University, Chicago, and colleagues reported.
“[T]here are limited data on normative TBE values,” the investigators wrote in Gastroenterology. “Furthermore, data supporting the accuracy of TBE as a screening test for esophageal motility disorders, as well as clinically relevant test thresholds, remains limited.”
TBE is conventionally interpreted using a handful of single measurements, most often the barium column height at 1, 2, or 5 minutes. Although these metrics are simple to obtain, variability in technique, cutoff values, and interpretation across centers limits reproducibility and weakens diagnostic accuracy, according to the investigators. The role of TBE has therefore been largely confined to adjudicating inconclusive manometry findings, but even in that setting, the absence of validated reference standards constrains its utility as a reliable screening tool.
To address this gap, Fass and colleagues conducted a prospective analysis of 290 patients who underwent TBE at Northwestern Memorial Hospital, Chicago, with HRM and FLIP panometry, interpreted according to the Chicago Classification version 4.0 (CCv4.0), serving as the diagnostic reference standards.
Patients were included if they had both TBE and manometry performed within a short interval, ensuring that the two tests could be meaningfully compared. The study population represented a broad spectrum of esophageal motility presentations, allowing the model to be trained on clinically relevant variation.
Beyond column height, the investigators measured barium height at multiple timepoints, maximal esophageal body width, maximum EGJ diameter, and tablet passage. These variables were incorporated into a recursive partitioning algorithm to build a multimetric classification tree aimed at distinguishing EGJ outflow obstruction from other motility disorders.
The optimal tree incorporated three sequential decision levels. At the top was maximum esophageal body width, followed by EGJ diameter and barium height at the second level, and tablet passage at the third. This stepwise structure allowed the model to refine diagnoses by combining simple, reproducible TBE metrics that are already collected in routine practice.
Among the 290 patients, 121 (42%) had EGJ outflow disorders, 151 (52%) had no outflow disorder, and 18 (6%) had inconclusive manometry findings. Using conventional interpretation with column height and tablet passage, TBE demonstrated a sensitivity of 77.8%, a specificity of 86.0%, and an accuracy of 82.2%. The multimetric classification tree improved diagnostic performance across all parameters, with a sensitivity of 84.2%, a specificity of 92.1%, and an accuracy of 88.3%.
The advantages of multimetric interpretation were most notable in patients with borderline column heights, which single-metric approaches often misclassify, underscoring the value of integrating multiple measurements into a unified model.
“[T]his study demonstrated that TBE can accurately identify achalasia when analyzed using multiple metrics in a classification tree model,” Fass and colleagues wrote. “Future studies should explore the use of TBE metrics and models to identify more specific esophageal motor disorders (such as esophageal spasm and absent contractility), as well as validation in a larger, multicenter cohort.”
Clinical Takeaways
Rishi Naik, MD, of the Center for Swallowing and Esophageal Disorders, Vanderbilt University Medical Center, Nashville, Tennessee, said the study represents a step forward in how clinicians can use a widely accessible esophageal imaging test.
“This study is important in that it has updated the way we use a very common, readily available imaging test and compared it to the current gold standard of HRM and FLIP,” he told GI & Hepatology News. “This provides a practical, standardized framework for clinicians evaluating patients with suspected esophageal motility disorders.”
Naik noted that while HRM and FLIP provide highly detailed information, both carry drawbacks that limit their universal adoption.
“Practically, HRM is a transnasal test that can be cumbersome, and FLIP is performed during a sedated procedure,” he said. “From a comfort and cost perspective, the esophagram outcompetes. What the TBE lacked was adequate sensitivity and specificity when just looking at column height, which is how the authors overcame this by leveraging the comparisons using CCv4.0.”
Implementation, however, requires discipline.
“A timed barium esophagram is a protocol, not a single esophagram,” Naik said. “Without proper measurements, you can’t follow the decision tree.”
Still, he pointed to radiology’s increasing adoption of artificial intelligence (AI) as a promising way forward.
“AI has already transformed radiological reads, and I’m optimistic it will eventually allow us to incorporate not only width, height, and tablet clearance but also 3D [three-dimensional] reconstructions of bolus retention and pressure to enhance predictive modeling,” Naik said.
This study was supported by the Public Health Service.
The investigators disclosed having relationships with Takeda, Phathom Pharmaceuticals, Medtronic, and others. Naik is a consultant for Sanofi/Regeneron, Eli Lilly and Company, and Renexxion.
A version of this article appeared on Medscape.com.
FROM GASTROENTEROLOGY
Medicolegal Concerns in Contemporary Private GI Practice
The need for gastroenterology (GI) services is on the rise in the US, with growing rates of colonoscopy, earlier-onset colon cancer, and inflammatory bowel disease. This increase is taking place in the context of a changing regulatory landscape.
, and to that end, a recent educational practice management update was published in Clinical Gastroenterology and Hepatology by Erin Smith Aebel, JD, a health law specialist with Trenam Law in Tampa, Florida. Aebel has been a speaker at several national GI conferences and has addressed GI trainees on these issues in medical schools.
“Healthcare regulation continues to evolve and it’s a complicated area,” Aebel told GI & Hepatology News. “Some physician investors in healthcare ventures see the potential profits but are not fully aware of how a physician’s license and livelihood could be affected by noncompliance.”
Aebel has seen some medical business owners and institutions pushing physicians to their limits in order to maximize profits. “They’re failing to allow them the meaningful things that allow for a long-term productive and successful practice that provides great patient care,” she said. “A current issue I’m dealing with is employers’ taking away physicians’ administrative time and not respecting the work that is necessary for the physician to be efficient and provide great care,” she said. “If too many physicians get squeezed in this manner, they will eventually walk away from big employers to something they can better control.”
Aebel noted that private-equity acquisitions of medical practices — a fast-growing US trend — are often targeted at quick profits and quick exits, which can be inconsistent with quality long-term patient care. “A question to be asked by physicians and patients is who is benefiting from this transaction?” she said. “Sometimes retired physicians can see a great benefit in private equity, but newer physicians can get tied up with a strong noncompete agreement. The best deals are ones that try to find wins for all involved, including patients.”
Many independent gastroenterologists focusing on the demands of daily practice are less aware than they should be of the legal and business administration sides. “I often get clients who come to me complaining about their contracts after they’ve signed them. I don’t have leverage to do as much for them,” she admitted.
From a business standpoint, gastroenterologists need to understand where they can negotiate for financial gain and control. These could relate to compensation and bonuses, as well as opportunities to invest in the practice, the practice management company, and possibly real estate or ambulatory surgery centers (ASCs).
Aebel’s overarching messages to gastroenterologists are as follows: “Be aware. Learn basic health law. Read your contracts before you sign them. And invest in good counsel before you sign agreements,” she said. “In addition, GI practitioners need to have a working knowledge of the federal Anti-Kickback Statute and the federal Stark Law and how they could be commonly applied in their practices.”
These are designed to protect government-funded patient care from monetary influence. The False Claims Act is another federal buttress against fraud and abuse, she said.
Update Details
Though not intended to be legal advice, Aebel’s update touches on several important medicolegal areas.
Stark Law on Self-Referrals
Gastroenterologists should be familiar with this federal law, a self-referral civil penalty statute regulating how physicians can pay themselves in practices that provide designated health services covered by federal healthcare programs such as Medicare or Medicaid.
For a Stark penalty to apply, there must be a physician referral to an entity (eg, lab, hospital, nutrition service, physiotherapy or radiotherapy center) in which the physician or a close family member has a financial interest.
Ambulatory Surgery Centers
Another common area vulnerable to federal fraud and abuse regulation is investment in ASCs. “Generally speaking, it is a felony to pay or be paid anything of value for Medicare or Medicaid business referrals,” Aebel wrote. This provision relates to the general restriction of the federal AKB statute.
A gastroenterologist referring Medicare patients to a center where that physician has an investment could technically violate this law because the physician will receive profit distributions from the referral. In addition to constituting a felony with potential jail time, violation of this statute is grounds for substantial civil monetary penalties and/or exclusion from the government coverage program.
Fortunately, Aebel noted, legal safe harbors cover many financial relationships, including investment in an ASC. The financial arrangement is protected from prosecution if it meets five safe harbor requirements, including nondiscriminatory treatment of government-insured patients and physician investment unrelated to a center’s volume or the value of referrals. If even one aspect is not met, that will automatically constitute a crime.
“However, the government will look at facts and circumstances to determine whether there was an intent to pay for a referral,” Aebel wrote.
The safe harbor designates requirements for four types of ASCs: surgeon-owned, single-specialty, multispecialty, and hospital/physician ASCs.
Private-Equity Investment
With mergers and acquisitions of US medical practices and networks by private-equity firms becoming more common, gastroenterologists need to be aware of the legal issues involved in such investment.
Most states abide by corporate practice of medicine doctrines, which prohibit unlicensed people from direct ownership in a medical practice. These doctrines vary by state, but their primary goal is to ensure that medical decisions are made solely based on patient care and not influenced by corporate interests. The aim is to shield the physician-patient relationship from commercial influence.
“Accordingly, this creates additional complicated structures necessary for private-equity investment in gastroenterology practices,” Aebel wrote. Usually, such investors will invest in a management services organization (MSO), which takes much of the practice’s value via management fees. Gastroenterologists may or may not have an opportunity to invest in the practice and the MSO in this scenario.
Under corporate practice of medicine doctrine, physicians must control the clinical aspects of patient care. Therefore, some states may have restrictions on private-equity companies’ control of the use of medical devices, pricing, medical protocols, or other issues of patient care.
“This needs to be considered when reviewing the investment documents and structural documents proposed by private equity companies,” the advisory stated. From a business standpoint, gastroenterologists need to understand where they can negotiate for financial gain and control over their clinical practice. “This could relate to their compensation, bonuses, and investment opportunities in the practice, the practice management company, and possibly real estate or ASCs.”
Offering a gastroenterologist’s perspective on the paper, Camille Thélin, MD, MSc, an associate professor in the Division of Digestive Diseases and Health at the University of South Florida, Tampa, Florida, who also practices privately, said, that “what Erin Aebel reminds us is that the business side of GI can be just as tricky as the clinical side. Ancillary services like capsule studies or office labs fall under strict Stark rules, ASC ownership has Anti-Kickback Law restrictions, and private-equity deals may affect both your paycheck and your autonomy.”
Thélin’s main takeaway advice is that business opportunities can be valuable but carry real legal risks if not structured correctly. “This isn’t just abstract compliance law — it’s about protecting one’s ability to practice medicine, earn fairly, and avoid devastating penalties,” she told GI & Hepatology News. “This article reinforces the need for proactive legal review and careful structuring of business arrangements so physicians can focus on patient care without stumbling into avoidable legal pitfalls. With the right legal structure, ancillaries, ASCs, and private equity can strengthen your GI practice without risking compliance.”
The bottom line, said Aebel, is that gastroenterologists already in private practice or considering entering one must navigate a complex landscape of compliance and regulatory requirements — particularly when providing ancillary services, investing in ASCs, or engaging with private equity.
Understanding the Stark law, the AKB statute, and the intricacies of private-equity investment is essential to mitigate risks and avoid severe penalties, the advisory stressed. By proactively seeking expert legal and business guidance, gastroenterologists can structure their financial and ownership arrangements in a compliant manner, safeguarding their practices while capitalizing on growth opportunities.
This paper listed no external funding. Neither Aebel nor Thélin had any relevant conflicts of interest.
A version of this article appeared on Medscape.com.
The need for gastroenterology (GI) services is on the rise in the US, with growing rates of colonoscopy, earlier-onset colon cancer, and inflammatory bowel disease. This increase is taking place in the context of a changing regulatory landscape.
, and to that end, a recent educational practice management update was published in Clinical Gastroenterology and Hepatology by Erin Smith Aebel, JD, a health law specialist with Trenam Law in Tampa, Florida. Aebel has been a speaker at several national GI conferences and has addressed GI trainees on these issues in medical schools.
“Healthcare regulation continues to evolve and it’s a complicated area,” Aebel told GI & Hepatology News. “Some physician investors in healthcare ventures see the potential profits but are not fully aware of how a physician’s license and livelihood could be affected by noncompliance.”
Aebel has seen some medical business owners and institutions pushing physicians to their limits in order to maximize profits. “They’re failing to allow them the meaningful things that allow for a long-term productive and successful practice that provides great patient care,” she said. “A current issue I’m dealing with is employers’ taking away physicians’ administrative time and not respecting the work that is necessary for the physician to be efficient and provide great care,” she said. “If too many physicians get squeezed in this manner, they will eventually walk away from big employers to something they can better control.”
Aebel noted that private-equity acquisitions of medical practices — a fast-growing US trend — are often targeted at quick profits and quick exits, which can be inconsistent with quality long-term patient care. “A question to be asked by physicians and patients is who is benefiting from this transaction?” she said. “Sometimes retired physicians can see a great benefit in private equity, but newer physicians can get tied up with a strong noncompete agreement. The best deals are ones that try to find wins for all involved, including patients.”
Many independent gastroenterologists focusing on the demands of daily practice are less aware than they should be of the legal and business administration sides. “I often get clients who come to me complaining about their contracts after they’ve signed them. I don’t have leverage to do as much for them,” she admitted.
From a business standpoint, gastroenterologists need to understand where they can negotiate for financial gain and control. These could relate to compensation and bonuses, as well as opportunities to invest in the practice, the practice management company, and possibly real estate or ambulatory surgery centers (ASCs).
Aebel’s overarching messages to gastroenterologists are as follows: “Be aware. Learn basic health law. Read your contracts before you sign them. And invest in good counsel before you sign agreements,” she said. “In addition, GI practitioners need to have a working knowledge of the federal Anti-Kickback Statute and the federal Stark Law and how they could be commonly applied in their practices.”
These are designed to protect government-funded patient care from monetary influence. The False Claims Act is another federal buttress against fraud and abuse, she said.
Update Details
Though not intended to be legal advice, Aebel’s update touches on several important medicolegal areas.
Stark Law on Self-Referrals
Gastroenterologists should be familiar with this federal law, a self-referral civil penalty statute regulating how physicians can pay themselves in practices that provide designated health services covered by federal healthcare programs such as Medicare or Medicaid.
For a Stark penalty to apply, there must be a physician referral to an entity (eg, lab, hospital, nutrition service, physiotherapy or radiotherapy center) in which the physician or a close family member has a financial interest.
Ambulatory Surgery Centers
Another common area vulnerable to federal fraud and abuse regulation is investment in ASCs. “Generally speaking, it is a felony to pay or be paid anything of value for Medicare or Medicaid business referrals,” Aebel wrote. This provision relates to the general restriction of the federal AKB statute.
A gastroenterologist referring Medicare patients to a center where that physician has an investment could technically violate this law because the physician will receive profit distributions from the referral. In addition to constituting a felony with potential jail time, violation of this statute is grounds for substantial civil monetary penalties and/or exclusion from the government coverage program.
Fortunately, Aebel noted, legal safe harbors cover many financial relationships, including investment in an ASC. The financial arrangement is protected from prosecution if it meets five safe harbor requirements, including nondiscriminatory treatment of government-insured patients and physician investment unrelated to a center’s volume or the value of referrals. If even one aspect is not met, that will automatically constitute a crime.
“However, the government will look at facts and circumstances to determine whether there was an intent to pay for a referral,” Aebel wrote.
The safe harbor designates requirements for four types of ASCs: surgeon-owned, single-specialty, multispecialty, and hospital/physician ASCs.
Private-Equity Investment
With mergers and acquisitions of US medical practices and networks by private-equity firms becoming more common, gastroenterologists need to be aware of the legal issues involved in such investment.
Most states abide by corporate practice of medicine doctrines, which prohibit unlicensed people from direct ownership in a medical practice. These doctrines vary by state, but their primary goal is to ensure that medical decisions are made solely based on patient care and not influenced by corporate interests. The aim is to shield the physician-patient relationship from commercial influence.
“Accordingly, this creates additional complicated structures necessary for private-equity investment in gastroenterology practices,” Aebel wrote. Usually, such investors will invest in a management services organization (MSO), which takes much of the practice’s value via management fees. Gastroenterologists may or may not have an opportunity to invest in the practice and the MSO in this scenario.
Under corporate practice of medicine doctrine, physicians must control the clinical aspects of patient care. Therefore, some states may have restrictions on private-equity companies’ control of the use of medical devices, pricing, medical protocols, or other issues of patient care.
“This needs to be considered when reviewing the investment documents and structural documents proposed by private equity companies,” the advisory stated. From a business standpoint, gastroenterologists need to understand where they can negotiate for financial gain and control over their clinical practice. “This could relate to their compensation, bonuses, and investment opportunities in the practice, the practice management company, and possibly real estate or ASCs.”
Offering a gastroenterologist’s perspective on the paper, Camille Thélin, MD, MSc, an associate professor in the Division of Digestive Diseases and Health at the University of South Florida, Tampa, Florida, who also practices privately, said, that “what Erin Aebel reminds us is that the business side of GI can be just as tricky as the clinical side. Ancillary services like capsule studies or office labs fall under strict Stark rules, ASC ownership has Anti-Kickback Law restrictions, and private-equity deals may affect both your paycheck and your autonomy.”
Thélin’s main takeaway advice is that business opportunities can be valuable but carry real legal risks if not structured correctly. “This isn’t just abstract compliance law — it’s about protecting one’s ability to practice medicine, earn fairly, and avoid devastating penalties,” she told GI & Hepatology News. “This article reinforces the need for proactive legal review and careful structuring of business arrangements so physicians can focus on patient care without stumbling into avoidable legal pitfalls. With the right legal structure, ancillaries, ASCs, and private equity can strengthen your GI practice without risking compliance.”
The bottom line, said Aebel, is that gastroenterologists already in private practice or considering entering one must navigate a complex landscape of compliance and regulatory requirements — particularly when providing ancillary services, investing in ASCs, or engaging with private equity.
Understanding the Stark law, the AKB statute, and the intricacies of private-equity investment is essential to mitigate risks and avoid severe penalties, the advisory stressed. By proactively seeking expert legal and business guidance, gastroenterologists can structure their financial and ownership arrangements in a compliant manner, safeguarding their practices while capitalizing on growth opportunities.
This paper listed no external funding. Neither Aebel nor Thélin had any relevant conflicts of interest.
A version of this article appeared on Medscape.com.
The need for gastroenterology (GI) services is on the rise in the US, with growing rates of colonoscopy, earlier-onset colon cancer, and inflammatory bowel disease. This increase is taking place in the context of a changing regulatory landscape.
, and to that end, a recent educational practice management update was published in Clinical Gastroenterology and Hepatology by Erin Smith Aebel, JD, a health law specialist with Trenam Law in Tampa, Florida. Aebel has been a speaker at several national GI conferences and has addressed GI trainees on these issues in medical schools.
“Healthcare regulation continues to evolve and it’s a complicated area,” Aebel told GI & Hepatology News. “Some physician investors in healthcare ventures see the potential profits but are not fully aware of how a physician’s license and livelihood could be affected by noncompliance.”
Aebel has seen some medical business owners and institutions pushing physicians to their limits in order to maximize profits. “They’re failing to allow them the meaningful things that allow for a long-term productive and successful practice that provides great patient care,” she said. “A current issue I’m dealing with is employers’ taking away physicians’ administrative time and not respecting the work that is necessary for the physician to be efficient and provide great care,” she said. “If too many physicians get squeezed in this manner, they will eventually walk away from big employers to something they can better control.”
Aebel noted that private-equity acquisitions of medical practices — a fast-growing US trend — are often targeted at quick profits and quick exits, which can be inconsistent with quality long-term patient care. “A question to be asked by physicians and patients is who is benefiting from this transaction?” she said. “Sometimes retired physicians can see a great benefit in private equity, but newer physicians can get tied up with a strong noncompete agreement. The best deals are ones that try to find wins for all involved, including patients.”
Many independent gastroenterologists focusing on the demands of daily practice are less aware than they should be of the legal and business administration sides. “I often get clients who come to me complaining about their contracts after they’ve signed them. I don’t have leverage to do as much for them,” she admitted.
From a business standpoint, gastroenterologists need to understand where they can negotiate for financial gain and control. These could relate to compensation and bonuses, as well as opportunities to invest in the practice, the practice management company, and possibly real estate or ambulatory surgery centers (ASCs).
Aebel’s overarching messages to gastroenterologists are as follows: “Be aware. Learn basic health law. Read your contracts before you sign them. And invest in good counsel before you sign agreements,” she said. “In addition, GI practitioners need to have a working knowledge of the federal Anti-Kickback Statute and the federal Stark Law and how they could be commonly applied in their practices.”
These are designed to protect government-funded patient care from monetary influence. The False Claims Act is another federal buttress against fraud and abuse, she said.
Update Details
Though not intended to be legal advice, Aebel’s update touches on several important medicolegal areas.
Stark Law on Self-Referrals
Gastroenterologists should be familiar with this federal law, a self-referral civil penalty statute regulating how physicians can pay themselves in practices that provide designated health services covered by federal healthcare programs such as Medicare or Medicaid.
For a Stark penalty to apply, there must be a physician referral to an entity (eg, lab, hospital, nutrition service, physiotherapy or radiotherapy center) in which the physician or a close family member has a financial interest.
Ambulatory Surgery Centers
Another common area vulnerable to federal fraud and abuse regulation is investment in ASCs. “Generally speaking, it is a felony to pay or be paid anything of value for Medicare or Medicaid business referrals,” Aebel wrote. This provision relates to the general restriction of the federal AKB statute.
A gastroenterologist referring Medicare patients to a center where that physician has an investment could technically violate this law because the physician will receive profit distributions from the referral. In addition to constituting a felony with potential jail time, violation of this statute is grounds for substantial civil monetary penalties and/or exclusion from the government coverage program.
Fortunately, Aebel noted, legal safe harbors cover many financial relationships, including investment in an ASC. The financial arrangement is protected from prosecution if it meets five safe harbor requirements, including nondiscriminatory treatment of government-insured patients and physician investment unrelated to a center’s volume or the value of referrals. If even one aspect is not met, that will automatically constitute a crime.
“However, the government will look at facts and circumstances to determine whether there was an intent to pay for a referral,” Aebel wrote.
The safe harbor designates requirements for four types of ASCs: surgeon-owned, single-specialty, multispecialty, and hospital/physician ASCs.
Private-Equity Investment
With mergers and acquisitions of US medical practices and networks by private-equity firms becoming more common, gastroenterologists need to be aware of the legal issues involved in such investment.
Most states abide by corporate practice of medicine doctrines, which prohibit unlicensed people from direct ownership in a medical practice. These doctrines vary by state, but their primary goal is to ensure that medical decisions are made solely based on patient care and not influenced by corporate interests. The aim is to shield the physician-patient relationship from commercial influence.
“Accordingly, this creates additional complicated structures necessary for private-equity investment in gastroenterology practices,” Aebel wrote. Usually, such investors will invest in a management services organization (MSO), which takes much of the practice’s value via management fees. Gastroenterologists may or may not have an opportunity to invest in the practice and the MSO in this scenario.
Under corporate practice of medicine doctrine, physicians must control the clinical aspects of patient care. Therefore, some states may have restrictions on private-equity companies’ control of the use of medical devices, pricing, medical protocols, or other issues of patient care.
“This needs to be considered when reviewing the investment documents and structural documents proposed by private equity companies,” the advisory stated. From a business standpoint, gastroenterologists need to understand where they can negotiate for financial gain and control over their clinical practice. “This could relate to their compensation, bonuses, and investment opportunities in the practice, the practice management company, and possibly real estate or ASCs.”
Offering a gastroenterologist’s perspective on the paper, Camille Thélin, MD, MSc, an associate professor in the Division of Digestive Diseases and Health at the University of South Florida, Tampa, Florida, who also practices privately, said, that “what Erin Aebel reminds us is that the business side of GI can be just as tricky as the clinical side. Ancillary services like capsule studies or office labs fall under strict Stark rules, ASC ownership has Anti-Kickback Law restrictions, and private-equity deals may affect both your paycheck and your autonomy.”
Thélin’s main takeaway advice is that business opportunities can be valuable but carry real legal risks if not structured correctly. “This isn’t just abstract compliance law — it’s about protecting one’s ability to practice medicine, earn fairly, and avoid devastating penalties,” she told GI & Hepatology News. “This article reinforces the need for proactive legal review and careful structuring of business arrangements so physicians can focus on patient care without stumbling into avoidable legal pitfalls. With the right legal structure, ancillaries, ASCs, and private equity can strengthen your GI practice without risking compliance.”
The bottom line, said Aebel, is that gastroenterologists already in private practice or considering entering one must navigate a complex landscape of compliance and regulatory requirements — particularly when providing ancillary services, investing in ASCs, or engaging with private equity.
Understanding the Stark law, the AKB statute, and the intricacies of private-equity investment is essential to mitigate risks and avoid severe penalties, the advisory stressed. By proactively seeking expert legal and business guidance, gastroenterologists can structure their financial and ownership arrangements in a compliant manner, safeguarding their practices while capitalizing on growth opportunities.
This paper listed no external funding. Neither Aebel nor Thélin had any relevant conflicts of interest.
A version of this article appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Are Probiotics for Pouchitis Prevention Worth the Cost?
, but its cost-effectiveness depends on relapse risk and may only be justified in patients who experience frequent relapses of pouchitis, a new analysis showed.
“Our findings highlight that while probiotic treatments can reduce the risk of this complication, their high costs limit their overall value for most patients,” lead author Gaurav Syal, MD, a gastroenterologist at UCLA Health, said in a statement.
“Our analysis can help guide shared decision-making between patients, clinicians, and payers to ensure resources are used where they can provide the most benefit,” Syal added.
The study was published online in Gastro Hep Advances.
Common Complication After Ulcerative Colitis Surgery
Pouchitis is a common complication in patients with ulcerative colitis who undergo restorative proctocolectomy with IPAA, with a cumulative incidence of around 48% at 2 years and 80% at 30 years.
Many patients who experience pouchitis have a single episode and respond well to short antibiotic courses. However, others develop recurrent or relapsing pouchitis, and 17% progress to a chronic form that can become dependent on antibiotics or refractory to antibiotics.
An eight-strain probiotic was shown to be effective in primary and secondary prevention of pouchitis in randomized, placebo-controlled trials.
Syal and colleagues sought to determine whether it’s worth the cost.
They constructed decision-tree models with Markov simulations to compare the risk for initial development and recurrence of pouchitis over a 2-year period between no prophylaxis and daily use of the eight-strain probiotic.
In the primary prophylaxis model, the cycle length was 2 weeks and pouchitis treatment sequence was ciprofloxacin, metronidazole and ciprofloxacin-tinidazole. In the secondary prophylaxis model, the cycle length was 4 weeks and pouchitis treatment sequence was initially the same as the primary prophylaxis model with the addition of vedolizumab and infliximab.
Costs were calculated from a US third-party payer perspective, using a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY).
For primary prevention, the probiotic slightly increased QALYs compared with no probiotic (0.927 vs 0.918) but at a far higher cost ($2223 vs $299), resulting in an incremental cost-effectiveness ratio (ICER) of $236,076 per QALY — well above the accepted threshold.
In patients with infrequent relapses, probiotic use was slightly more effective than no use of probiotic (cumulative QALYs, 1.26 vs 1.24) but more expensive ($3370 vs $557), yielding an ICER of $153,011 per QALY — again above the accepted threshold.
However, sensitivity analyses revealed that the probiotic was cost-effective in patients with frequent relapsing pouchitis — defined as two or more episodes per year.
In this subgroup, the ICER dropped below the willingness-to-pay threshold of $100,000 per QALY, and in some scenarios, the probiotic even became the dominant strategy, meaning it was both more effective and less costly than no prophylaxis, the researchers noted.
Current guidelines from AGA on managing pouchitis suggest using probiotics to prevent recurrent episodes of pouchitis with a caveat that those who experience infrequent episodes may choose to avoid secondary prevention strategies.
“Our findings supplement the guidelines by confirming that the eight-strain probiotics can be cost-effective in frequent relapsing not in infrequent relapsing pouchitis,” the authors wrote.
They also noted that the probiotic cost itself was the biggest driver of results, accounting for 95% of the total cost in the primary prevention model. According to their analysis, reducing its price by half could make it a cost-effective option more broadly.
They also noted that probiotic prophylaxis could be cost-effective for patients at higher-than-average risk, such as those with primary sclerosing cholangitis (PSC), who have 4.2 times higher odds of developing pouchitis than peers without PSC.
But they cautioned that “further research is warranted on the effectiveness of the eight-strain probiotic for primary prevention of pouchitis in patients with ulcerative colitis and IPAA and PSC.”
The study had no financial support. Syal reported receiving research support from Pfizer.
A version of this article appeared on Medscape.com.
, but its cost-effectiveness depends on relapse risk and may only be justified in patients who experience frequent relapses of pouchitis, a new analysis showed.
“Our findings highlight that while probiotic treatments can reduce the risk of this complication, their high costs limit their overall value for most patients,” lead author Gaurav Syal, MD, a gastroenterologist at UCLA Health, said in a statement.
“Our analysis can help guide shared decision-making between patients, clinicians, and payers to ensure resources are used where they can provide the most benefit,” Syal added.
The study was published online in Gastro Hep Advances.
Common Complication After Ulcerative Colitis Surgery
Pouchitis is a common complication in patients with ulcerative colitis who undergo restorative proctocolectomy with IPAA, with a cumulative incidence of around 48% at 2 years and 80% at 30 years.
Many patients who experience pouchitis have a single episode and respond well to short antibiotic courses. However, others develop recurrent or relapsing pouchitis, and 17% progress to a chronic form that can become dependent on antibiotics or refractory to antibiotics.
An eight-strain probiotic was shown to be effective in primary and secondary prevention of pouchitis in randomized, placebo-controlled trials.
Syal and colleagues sought to determine whether it’s worth the cost.
They constructed decision-tree models with Markov simulations to compare the risk for initial development and recurrence of pouchitis over a 2-year period between no prophylaxis and daily use of the eight-strain probiotic.
In the primary prophylaxis model, the cycle length was 2 weeks and pouchitis treatment sequence was ciprofloxacin, metronidazole and ciprofloxacin-tinidazole. In the secondary prophylaxis model, the cycle length was 4 weeks and pouchitis treatment sequence was initially the same as the primary prophylaxis model with the addition of vedolizumab and infliximab.
Costs were calculated from a US third-party payer perspective, using a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY).
For primary prevention, the probiotic slightly increased QALYs compared with no probiotic (0.927 vs 0.918) but at a far higher cost ($2223 vs $299), resulting in an incremental cost-effectiveness ratio (ICER) of $236,076 per QALY — well above the accepted threshold.
In patients with infrequent relapses, probiotic use was slightly more effective than no use of probiotic (cumulative QALYs, 1.26 vs 1.24) but more expensive ($3370 vs $557), yielding an ICER of $153,011 per QALY — again above the accepted threshold.
However, sensitivity analyses revealed that the probiotic was cost-effective in patients with frequent relapsing pouchitis — defined as two or more episodes per year.
In this subgroup, the ICER dropped below the willingness-to-pay threshold of $100,000 per QALY, and in some scenarios, the probiotic even became the dominant strategy, meaning it was both more effective and less costly than no prophylaxis, the researchers noted.
Current guidelines from AGA on managing pouchitis suggest using probiotics to prevent recurrent episodes of pouchitis with a caveat that those who experience infrequent episodes may choose to avoid secondary prevention strategies.
“Our findings supplement the guidelines by confirming that the eight-strain probiotics can be cost-effective in frequent relapsing not in infrequent relapsing pouchitis,” the authors wrote.
They also noted that the probiotic cost itself was the biggest driver of results, accounting for 95% of the total cost in the primary prevention model. According to their analysis, reducing its price by half could make it a cost-effective option more broadly.
They also noted that probiotic prophylaxis could be cost-effective for patients at higher-than-average risk, such as those with primary sclerosing cholangitis (PSC), who have 4.2 times higher odds of developing pouchitis than peers without PSC.
But they cautioned that “further research is warranted on the effectiveness of the eight-strain probiotic for primary prevention of pouchitis in patients with ulcerative colitis and IPAA and PSC.”
The study had no financial support. Syal reported receiving research support from Pfizer.
A version of this article appeared on Medscape.com.
, but its cost-effectiveness depends on relapse risk and may only be justified in patients who experience frequent relapses of pouchitis, a new analysis showed.
“Our findings highlight that while probiotic treatments can reduce the risk of this complication, their high costs limit their overall value for most patients,” lead author Gaurav Syal, MD, a gastroenterologist at UCLA Health, said in a statement.
“Our analysis can help guide shared decision-making between patients, clinicians, and payers to ensure resources are used where they can provide the most benefit,” Syal added.
The study was published online in Gastro Hep Advances.
Common Complication After Ulcerative Colitis Surgery
Pouchitis is a common complication in patients with ulcerative colitis who undergo restorative proctocolectomy with IPAA, with a cumulative incidence of around 48% at 2 years and 80% at 30 years.
Many patients who experience pouchitis have a single episode and respond well to short antibiotic courses. However, others develop recurrent or relapsing pouchitis, and 17% progress to a chronic form that can become dependent on antibiotics or refractory to antibiotics.
An eight-strain probiotic was shown to be effective in primary and secondary prevention of pouchitis in randomized, placebo-controlled trials.
Syal and colleagues sought to determine whether it’s worth the cost.
They constructed decision-tree models with Markov simulations to compare the risk for initial development and recurrence of pouchitis over a 2-year period between no prophylaxis and daily use of the eight-strain probiotic.
In the primary prophylaxis model, the cycle length was 2 weeks and pouchitis treatment sequence was ciprofloxacin, metronidazole and ciprofloxacin-tinidazole. In the secondary prophylaxis model, the cycle length was 4 weeks and pouchitis treatment sequence was initially the same as the primary prophylaxis model with the addition of vedolizumab and infliximab.
Costs were calculated from a US third-party payer perspective, using a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY).
For primary prevention, the probiotic slightly increased QALYs compared with no probiotic (0.927 vs 0.918) but at a far higher cost ($2223 vs $299), resulting in an incremental cost-effectiveness ratio (ICER) of $236,076 per QALY — well above the accepted threshold.
In patients with infrequent relapses, probiotic use was slightly more effective than no use of probiotic (cumulative QALYs, 1.26 vs 1.24) but more expensive ($3370 vs $557), yielding an ICER of $153,011 per QALY — again above the accepted threshold.
However, sensitivity analyses revealed that the probiotic was cost-effective in patients with frequent relapsing pouchitis — defined as two or more episodes per year.
In this subgroup, the ICER dropped below the willingness-to-pay threshold of $100,000 per QALY, and in some scenarios, the probiotic even became the dominant strategy, meaning it was both more effective and less costly than no prophylaxis, the researchers noted.
Current guidelines from AGA on managing pouchitis suggest using probiotics to prevent recurrent episodes of pouchitis with a caveat that those who experience infrequent episodes may choose to avoid secondary prevention strategies.
“Our findings supplement the guidelines by confirming that the eight-strain probiotics can be cost-effective in frequent relapsing not in infrequent relapsing pouchitis,” the authors wrote.
They also noted that the probiotic cost itself was the biggest driver of results, accounting for 95% of the total cost in the primary prevention model. According to their analysis, reducing its price by half could make it a cost-effective option more broadly.
They also noted that probiotic prophylaxis could be cost-effective for patients at higher-than-average risk, such as those with primary sclerosing cholangitis (PSC), who have 4.2 times higher odds of developing pouchitis than peers without PSC.
But they cautioned that “further research is warranted on the effectiveness of the eight-strain probiotic for primary prevention of pouchitis in patients with ulcerative colitis and IPAA and PSC.”
The study had no financial support. Syal reported receiving research support from Pfizer.
A version of this article appeared on Medscape.com.
FROM GASTRO HEP ADVANCES
Large Language Models Cut Time, Cost of Guideline Development
, according to a pilot study from the American Gastroenterological Association (AGA).
Faster, cheaper study screening could allow societies to update clinical recommendations more frequently, improving alignment with the latest evidence, lead author Sunny Chung, MD, of Yale School of Medicine, New Haven, Connecticut, and colleagues, reported.
“Each guideline typically requires 5 to 15 systematic reviews, making the process time-consuming (averaging more than 60 weeks) and costly (more than $140,000),” the investigators wrote in Gastroenterology . “One of the most critical yet time-consuming steps in systematic reviews is title and abstract screening. LLMs have the potential to make this step more efficient.”
To test this approach, the investigators developed, validated, and applied a dual-model LLM screening pipeline with human-in-the-loop oversight, focusing on randomized controlled trials in AGA guidelines.
The system was built using the 2021 guideline on moderate-to-severe Crohn’s disease, targeting biologic therapies for induction and maintenance of remission.
Using chain-of-thought prompting and structured inclusion criteria based on the PICO framework, the investigators deployed GPT-4o (OpenAI) and Gemini-1.5-Pro (Google DeepMind) as independent screeners, each assessing titles and abstracts according to standardized logic encoded in JavaScript Object Notation. This approach mimicked a traditional double-reviewer system.
After initial testing, the pipeline was validated in a 2025 update of the same guideline, this time spanning 6 focused clinical questions on advanced therapies and immunomodulators. Results were compared against manual screening by 2 experienced human reviewers, with total screening time documented.
The system was then tested across 4 additional guideline topics: fecal microbiota transplantation (FMT) for irritable bowel syndrome and Clostridioides difficile, gastroparesis, and hepatocellular carcinoma. A final test applied the system to a forthcoming guideline on complications of acute pancreatitis.
Across all topics, the dual-LLM system achieved 100% sensitivity in identifying randomized controlled trials (RCTs). For the 2025 update of the AGA guideline on Crohn’s disease, the models flagged 418 of 4,377 abstracts for inclusion, captur-ing all 25 relevant RCTs in just 48 minutes. Manual screening of the same dataset previously took almost 13 hours.
Comparable accuracy and time savings were observed for the other topics.
The pipeline correctly flagged all 13 RCTs in 4,820 studies on FMT for irritable bowel syndrome, and all 16 RCTs in 5,587 studies on FMT for Clostridioides difficile, requiring 27 and 66 minutes, respectively. Similarly, the system captured all 11 RCTs in 3,919 hepatocellular carcinoma abstracts and all 18 RCTs in 1,578 studies on gastroparesis, completing each task in under 65 minutes. Early testing on the upcoming guideline for pancreatitis yielded similar results.
Cost analysis underscored the efficiency of this approach. At an estimated $175–200 per hour for expert screeners, traditional abstract screening would cost around $2,500 per review, versus approximately $100 for the LLM approach—a 96% reduction.
The investigators cautioned that human oversight remains necessary to verify the relevance of studies flagged by the models. While the system’s sensitivity was consistent, it also selected articles that were ultimately excluded by expert reviewers. Broader validation will be required to assess performance across non-RCT study designs, such as observational or case-control studies, they added.
“As medical literature continues to expand, the integration of artificial intelligence into evidence synthesis processes will become increasingly vital,” Dr. Chung and colleagues wrote. “With further refinement and broader validation, this LLM-based pipeline has the potential to revolutionize evidence synthesis and set a new standard for guideline development.”
This study was funded by National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. The investigators reported no conflicts of interest.
Ethan Goh, MD, executive director of the Stanford AI Research and Science Evaluation (ARISE) Network, described the AGA pilot as both timely and promising.
“I’m certainly bullish about the use case,” he said in an interview. “Their study design and application is also robust, so I would congratulate them.”
Goh, a general editor for BMJ Digital Health & AI, predicted “huge potential” in the strategy for both clinicians and the general population, who benefit from the most up-to-date guidelines possible.
“I believe that using AI can represent a much faster, more cost effective, efficient way of gathering all these information sources,” he said.
Still, humans will need to be involved in the process.
“[This AI-driven approach] will always need some degree of expert oversight and judgement,” Goh said.
Speaking more broadly about automating study aggregation, Goh said AI may still struggle to determine which studies are most clinically relevant.
“When we use [AI models] to pull out medical references, anecdotally, I don’t think they’re always getting the best ones all the time, or even necessarily the right ones,” he said.
And as AI models grow more impressive, these shortcomings become less apparent, potentially lulling humans into overconfidence.
“Humans are humans,” Goh said. “We get lazy over time. That will be one of the challenges. As the systems get increasingly good, humans start to defer more and more of their judgment to them and say, ‘All right, AI, you’re doing good. Just do 100% automation.’ And then [people] start fact checking or reviewing even less.”
AI could also undermine automated reviews in another way: AI-generated publications that appear genuine, but aren’t, may creep into the dataset.
Despite these concerns, Goh concluded on an optimistic note.
“I think that there are huge ways to use AI, tools, not to replace, but to augment and support human judgment,” he said.
Ethan Goh, MD, is senior research engineer and executive director of the Stanford AI Research and Science Evaluation (ARISE) Network, at Stanford (Calif.) University. He declared no conflicts of interest.
Ethan Goh, MD, executive director of the Stanford AI Research and Science Evaluation (ARISE) Network, described the AGA pilot as both timely and promising.
“I’m certainly bullish about the use case,” he said in an interview. “Their study design and application is also robust, so I would congratulate them.”
Goh, a general editor for BMJ Digital Health & AI, predicted “huge potential” in the strategy for both clinicians and the general population, who benefit from the most up-to-date guidelines possible.
“I believe that using AI can represent a much faster, more cost effective, efficient way of gathering all these information sources,” he said.
Still, humans will need to be involved in the process.
“[This AI-driven approach] will always need some degree of expert oversight and judgement,” Goh said.
Speaking more broadly about automating study aggregation, Goh said AI may still struggle to determine which studies are most clinically relevant.
“When we use [AI models] to pull out medical references, anecdotally, I don’t think they’re always getting the best ones all the time, or even necessarily the right ones,” he said.
And as AI models grow more impressive, these shortcomings become less apparent, potentially lulling humans into overconfidence.
“Humans are humans,” Goh said. “We get lazy over time. That will be one of the challenges. As the systems get increasingly good, humans start to defer more and more of their judgment to them and say, ‘All right, AI, you’re doing good. Just do 100% automation.’ And then [people] start fact checking or reviewing even less.”
AI could also undermine automated reviews in another way: AI-generated publications that appear genuine, but aren’t, may creep into the dataset.
Despite these concerns, Goh concluded on an optimistic note.
“I think that there are huge ways to use AI, tools, not to replace, but to augment and support human judgment,” he said.
Ethan Goh, MD, is senior research engineer and executive director of the Stanford AI Research and Science Evaluation (ARISE) Network, at Stanford (Calif.) University. He declared no conflicts of interest.
Ethan Goh, MD, executive director of the Stanford AI Research and Science Evaluation (ARISE) Network, described the AGA pilot as both timely and promising.
“I’m certainly bullish about the use case,” he said in an interview. “Their study design and application is also robust, so I would congratulate them.”
Goh, a general editor for BMJ Digital Health & AI, predicted “huge potential” in the strategy for both clinicians and the general population, who benefit from the most up-to-date guidelines possible.
“I believe that using AI can represent a much faster, more cost effective, efficient way of gathering all these information sources,” he said.
Still, humans will need to be involved in the process.
“[This AI-driven approach] will always need some degree of expert oversight and judgement,” Goh said.
Speaking more broadly about automating study aggregation, Goh said AI may still struggle to determine which studies are most clinically relevant.
“When we use [AI models] to pull out medical references, anecdotally, I don’t think they’re always getting the best ones all the time, or even necessarily the right ones,” he said.
And as AI models grow more impressive, these shortcomings become less apparent, potentially lulling humans into overconfidence.
“Humans are humans,” Goh said. “We get lazy over time. That will be one of the challenges. As the systems get increasingly good, humans start to defer more and more of their judgment to them and say, ‘All right, AI, you’re doing good. Just do 100% automation.’ And then [people] start fact checking or reviewing even less.”
AI could also undermine automated reviews in another way: AI-generated publications that appear genuine, but aren’t, may creep into the dataset.
Despite these concerns, Goh concluded on an optimistic note.
“I think that there are huge ways to use AI, tools, not to replace, but to augment and support human judgment,” he said.
Ethan Goh, MD, is senior research engineer and executive director of the Stanford AI Research and Science Evaluation (ARISE) Network, at Stanford (Calif.) University. He declared no conflicts of interest.
, according to a pilot study from the American Gastroenterological Association (AGA).
Faster, cheaper study screening could allow societies to update clinical recommendations more frequently, improving alignment with the latest evidence, lead author Sunny Chung, MD, of Yale School of Medicine, New Haven, Connecticut, and colleagues, reported.
“Each guideline typically requires 5 to 15 systematic reviews, making the process time-consuming (averaging more than 60 weeks) and costly (more than $140,000),” the investigators wrote in Gastroenterology . “One of the most critical yet time-consuming steps in systematic reviews is title and abstract screening. LLMs have the potential to make this step more efficient.”
To test this approach, the investigators developed, validated, and applied a dual-model LLM screening pipeline with human-in-the-loop oversight, focusing on randomized controlled trials in AGA guidelines.
The system was built using the 2021 guideline on moderate-to-severe Crohn’s disease, targeting biologic therapies for induction and maintenance of remission.
Using chain-of-thought prompting and structured inclusion criteria based on the PICO framework, the investigators deployed GPT-4o (OpenAI) and Gemini-1.5-Pro (Google DeepMind) as independent screeners, each assessing titles and abstracts according to standardized logic encoded in JavaScript Object Notation. This approach mimicked a traditional double-reviewer system.
After initial testing, the pipeline was validated in a 2025 update of the same guideline, this time spanning 6 focused clinical questions on advanced therapies and immunomodulators. Results were compared against manual screening by 2 experienced human reviewers, with total screening time documented.
The system was then tested across 4 additional guideline topics: fecal microbiota transplantation (FMT) for irritable bowel syndrome and Clostridioides difficile, gastroparesis, and hepatocellular carcinoma. A final test applied the system to a forthcoming guideline on complications of acute pancreatitis.
Across all topics, the dual-LLM system achieved 100% sensitivity in identifying randomized controlled trials (RCTs). For the 2025 update of the AGA guideline on Crohn’s disease, the models flagged 418 of 4,377 abstracts for inclusion, captur-ing all 25 relevant RCTs in just 48 minutes. Manual screening of the same dataset previously took almost 13 hours.
Comparable accuracy and time savings were observed for the other topics.
The pipeline correctly flagged all 13 RCTs in 4,820 studies on FMT for irritable bowel syndrome, and all 16 RCTs in 5,587 studies on FMT for Clostridioides difficile, requiring 27 and 66 minutes, respectively. Similarly, the system captured all 11 RCTs in 3,919 hepatocellular carcinoma abstracts and all 18 RCTs in 1,578 studies on gastroparesis, completing each task in under 65 minutes. Early testing on the upcoming guideline for pancreatitis yielded similar results.
Cost analysis underscored the efficiency of this approach. At an estimated $175–200 per hour for expert screeners, traditional abstract screening would cost around $2,500 per review, versus approximately $100 for the LLM approach—a 96% reduction.
The investigators cautioned that human oversight remains necessary to verify the relevance of studies flagged by the models. While the system’s sensitivity was consistent, it also selected articles that were ultimately excluded by expert reviewers. Broader validation will be required to assess performance across non-RCT study designs, such as observational or case-control studies, they added.
“As medical literature continues to expand, the integration of artificial intelligence into evidence synthesis processes will become increasingly vital,” Dr. Chung and colleagues wrote. “With further refinement and broader validation, this LLM-based pipeline has the potential to revolutionize evidence synthesis and set a new standard for guideline development.”
This study was funded by National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. The investigators reported no conflicts of interest.
, according to a pilot study from the American Gastroenterological Association (AGA).
Faster, cheaper study screening could allow societies to update clinical recommendations more frequently, improving alignment with the latest evidence, lead author Sunny Chung, MD, of Yale School of Medicine, New Haven, Connecticut, and colleagues, reported.
“Each guideline typically requires 5 to 15 systematic reviews, making the process time-consuming (averaging more than 60 weeks) and costly (more than $140,000),” the investigators wrote in Gastroenterology . “One of the most critical yet time-consuming steps in systematic reviews is title and abstract screening. LLMs have the potential to make this step more efficient.”
To test this approach, the investigators developed, validated, and applied a dual-model LLM screening pipeline with human-in-the-loop oversight, focusing on randomized controlled trials in AGA guidelines.
The system was built using the 2021 guideline on moderate-to-severe Crohn’s disease, targeting biologic therapies for induction and maintenance of remission.
Using chain-of-thought prompting and structured inclusion criteria based on the PICO framework, the investigators deployed GPT-4o (OpenAI) and Gemini-1.5-Pro (Google DeepMind) as independent screeners, each assessing titles and abstracts according to standardized logic encoded in JavaScript Object Notation. This approach mimicked a traditional double-reviewer system.
After initial testing, the pipeline was validated in a 2025 update of the same guideline, this time spanning 6 focused clinical questions on advanced therapies and immunomodulators. Results were compared against manual screening by 2 experienced human reviewers, with total screening time documented.
The system was then tested across 4 additional guideline topics: fecal microbiota transplantation (FMT) for irritable bowel syndrome and Clostridioides difficile, gastroparesis, and hepatocellular carcinoma. A final test applied the system to a forthcoming guideline on complications of acute pancreatitis.
Across all topics, the dual-LLM system achieved 100% sensitivity in identifying randomized controlled trials (RCTs). For the 2025 update of the AGA guideline on Crohn’s disease, the models flagged 418 of 4,377 abstracts for inclusion, captur-ing all 25 relevant RCTs in just 48 minutes. Manual screening of the same dataset previously took almost 13 hours.
Comparable accuracy and time savings were observed for the other topics.
The pipeline correctly flagged all 13 RCTs in 4,820 studies on FMT for irritable bowel syndrome, and all 16 RCTs in 5,587 studies on FMT for Clostridioides difficile, requiring 27 and 66 minutes, respectively. Similarly, the system captured all 11 RCTs in 3,919 hepatocellular carcinoma abstracts and all 18 RCTs in 1,578 studies on gastroparesis, completing each task in under 65 minutes. Early testing on the upcoming guideline for pancreatitis yielded similar results.
Cost analysis underscored the efficiency of this approach. At an estimated $175–200 per hour for expert screeners, traditional abstract screening would cost around $2,500 per review, versus approximately $100 for the LLM approach—a 96% reduction.
The investigators cautioned that human oversight remains necessary to verify the relevance of studies flagged by the models. While the system’s sensitivity was consistent, it also selected articles that were ultimately excluded by expert reviewers. Broader validation will be required to assess performance across non-RCT study designs, such as observational or case-control studies, they added.
“As medical literature continues to expand, the integration of artificial intelligence into evidence synthesis processes will become increasingly vital,” Dr. Chung and colleagues wrote. “With further refinement and broader validation, this LLM-based pipeline has the potential to revolutionize evidence synthesis and set a new standard for guideline development.”
This study was funded by National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. The investigators reported no conflicts of interest.
FROM GASTROENTEROLOGY
New Guidelines for Pregnancy and IBD Aim to Quell Fears
, suggesting this approach will not harm the fetus.
The guidelines also recommend that all women with IBD receive preconception counseling and be followed as high-risk pregnancies.
“Management of chronic illness in pregnant women has always been defined by fear of harming the fetus,” said Uma Mahadevan, MD, AGAF, director of the Colitis and Crohn’s Disease Center at the University of California San Francisco and chair of the Global Consensus Consortium that developed the guidelines.
As a result, pregnant women are excluded from clinical trials of experimental therapies for IBD. And when a new therapy achieves regulatory approval, there are no human pregnancy safety data, only animal data. To fill this gap, the PIANO study, of which Mahadevan is principal investigator, looked at the safety of IBD medications in pregnancy and short- and long-term outcomes of the children.
“With our ongoing work in pregnancy in the patient with IBD, we realized that inflammation in the mother is the leading cause of poor outcome for the infant,” she told GI & Hepatology News.
“We also have a better understanding of placental transfer of biologic agents” and the lack of exposure to the fetus during the first trimester, “a key period of organogenesis,” she added.
Final recommendations were published simultaneously in six international journals, namely, Clinical Gastroenterology and Hepatology, American Journal of Gastroenterology, GUT, Inflammatory Bowel Diseases, Journal of Crohn’s and Colitis, and Alimentary Pharmacology and Therapeutics.
Surprising, Novel Findings
Limited provider knowledge led to varied practices in caring for women with IBD who become pregnant, according to the consensus authors. Practices are affected by local dogma, available resources, individual interpretation of the literature, and fear of harming the fetus.
“The variations in guidelines by different societies and countries reflect this and lead to confusion for physicians and patients alike,” the authors of the guidelines wrote.
Therefore, the Global Consensus Consortium — a group of 39 IBD experts, including teratologists and maternal fetal medicine specialists and seven patient advocates from six continents — convened to review and assess current data and come to an agreement on best practices. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used when sufficient published data were available, and the Research and Development process when expert opinion was needed to guide consistent practice.
“Some of the findings were expected, but others were novel,” said Mahadevan.
Recommendations that might surprise clinicians include GRADE statement 9, which suggests that pregnant women with IBD take low-dose aspirin by 12 to 16 weeks’ gestation to prevent preterm preeclampsia. “This is based on the ASPRE study, showing that women at risk of preeclampsia can lower their risk by taking low-dose aspirin,” with no risk for flare, Mahadevan said.
In addition, GRADE statements 17-20 recommend/suggest that women continue their biologic throughout pregnancy without stopping. “North America has always recommended continuing during the third trimester, while Europe only recently has come to this,” Mahadevan said. “However, there was always some looseness about stopping at week X, Y, or Z. Now, we do recommend continuing the dose on schedule with no holding.”
Continuing medications considered low risk for use during pregnancy, such as 5-amino salicylic acids, sulfasalazine, thiopurines, and all monoclonal antibodies during preconception, pregnancy, and lactation, was also recommended.
However, small-molecule drugs such as S1P receptor molecules and JAK inhibitors should be avoided for at least 1 month, and in some cases for 3 months prior to attempting conception, unless there is no alternative for the health of the mother. They should also be avoided during lactation.
Grade statement 33, which suggests that live rotavirus vaccine may be provided in children with in utero exposure to biologics, is also new, Mahadevan noted. “All prior recommendations were that no live vaccine should be given in the first 6 months or longer if infants were exposed to biologics in utero, but based on a prospective Canadian study, there is no harm when given to these infants.”
Another novel recommendation is that women with IBD on any monoclonal antibodies, including newer interleukin-23s, may breastfeed even though there are not clinical trial data at this point. The recommendation to continue them through pregnancy and lactation is based on placental physiology, as well as on the physiology of monoclonal antibody transfer in breast milk, according to the consortium.
Furthermore, the authors noted, there was no increase in infant infections at 4 months or 12 months if they were exposed to a biologic or thiopurine (or both) during pregnancy.
Overall, the consortium recommended that all pregnancies for women with IBD be considered as “high risk” for complications. This is due to the fact that many parts of the world, including the US, are “resource-limited,” Mahadevan explained. Since maternal fetal medicine specialists are not widely available, the consortium suggested all these patients be followed with increased monitoring and surveillance based on available resources.
In addition to the guidelines, patient videos in seven languages, a professional slide deck in English and Spanish, and a video on the global consensus are all available at https://pianostudy.org/.
This study was funded by The Leona B. and Harry H. Helmsley Charitable Trust.
Mahadevan reported being a consultant for AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Celltrion, Enveda, Gilead, Janssen, Lilly, Merck, Pfizer, Protagonist, Roivant, and Takeda.
A version of this article appeared on Medscape.com.
, suggesting this approach will not harm the fetus.
The guidelines also recommend that all women with IBD receive preconception counseling and be followed as high-risk pregnancies.
“Management of chronic illness in pregnant women has always been defined by fear of harming the fetus,” said Uma Mahadevan, MD, AGAF, director of the Colitis and Crohn’s Disease Center at the University of California San Francisco and chair of the Global Consensus Consortium that developed the guidelines.
As a result, pregnant women are excluded from clinical trials of experimental therapies for IBD. And when a new therapy achieves regulatory approval, there are no human pregnancy safety data, only animal data. To fill this gap, the PIANO study, of which Mahadevan is principal investigator, looked at the safety of IBD medications in pregnancy and short- and long-term outcomes of the children.
“With our ongoing work in pregnancy in the patient with IBD, we realized that inflammation in the mother is the leading cause of poor outcome for the infant,” she told GI & Hepatology News.
“We also have a better understanding of placental transfer of biologic agents” and the lack of exposure to the fetus during the first trimester, “a key period of organogenesis,” she added.
Final recommendations were published simultaneously in six international journals, namely, Clinical Gastroenterology and Hepatology, American Journal of Gastroenterology, GUT, Inflammatory Bowel Diseases, Journal of Crohn’s and Colitis, and Alimentary Pharmacology and Therapeutics.
Surprising, Novel Findings
Limited provider knowledge led to varied practices in caring for women with IBD who become pregnant, according to the consensus authors. Practices are affected by local dogma, available resources, individual interpretation of the literature, and fear of harming the fetus.
“The variations in guidelines by different societies and countries reflect this and lead to confusion for physicians and patients alike,” the authors of the guidelines wrote.
Therefore, the Global Consensus Consortium — a group of 39 IBD experts, including teratologists and maternal fetal medicine specialists and seven patient advocates from six continents — convened to review and assess current data and come to an agreement on best practices. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used when sufficient published data were available, and the Research and Development process when expert opinion was needed to guide consistent practice.
“Some of the findings were expected, but others were novel,” said Mahadevan.
Recommendations that might surprise clinicians include GRADE statement 9, which suggests that pregnant women with IBD take low-dose aspirin by 12 to 16 weeks’ gestation to prevent preterm preeclampsia. “This is based on the ASPRE study, showing that women at risk of preeclampsia can lower their risk by taking low-dose aspirin,” with no risk for flare, Mahadevan said.
In addition, GRADE statements 17-20 recommend/suggest that women continue their biologic throughout pregnancy without stopping. “North America has always recommended continuing during the third trimester, while Europe only recently has come to this,” Mahadevan said. “However, there was always some looseness about stopping at week X, Y, or Z. Now, we do recommend continuing the dose on schedule with no holding.”
Continuing medications considered low risk for use during pregnancy, such as 5-amino salicylic acids, sulfasalazine, thiopurines, and all monoclonal antibodies during preconception, pregnancy, and lactation, was also recommended.
However, small-molecule drugs such as S1P receptor molecules and JAK inhibitors should be avoided for at least 1 month, and in some cases for 3 months prior to attempting conception, unless there is no alternative for the health of the mother. They should also be avoided during lactation.
Grade statement 33, which suggests that live rotavirus vaccine may be provided in children with in utero exposure to biologics, is also new, Mahadevan noted. “All prior recommendations were that no live vaccine should be given in the first 6 months or longer if infants were exposed to biologics in utero, but based on a prospective Canadian study, there is no harm when given to these infants.”
Another novel recommendation is that women with IBD on any monoclonal antibodies, including newer interleukin-23s, may breastfeed even though there are not clinical trial data at this point. The recommendation to continue them through pregnancy and lactation is based on placental physiology, as well as on the physiology of monoclonal antibody transfer in breast milk, according to the consortium.
Furthermore, the authors noted, there was no increase in infant infections at 4 months or 12 months if they were exposed to a biologic or thiopurine (or both) during pregnancy.
Overall, the consortium recommended that all pregnancies for women with IBD be considered as “high risk” for complications. This is due to the fact that many parts of the world, including the US, are “resource-limited,” Mahadevan explained. Since maternal fetal medicine specialists are not widely available, the consortium suggested all these patients be followed with increased monitoring and surveillance based on available resources.
In addition to the guidelines, patient videos in seven languages, a professional slide deck in English and Spanish, and a video on the global consensus are all available at https://pianostudy.org/.
This study was funded by The Leona B. and Harry H. Helmsley Charitable Trust.
Mahadevan reported being a consultant for AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Celltrion, Enveda, Gilead, Janssen, Lilly, Merck, Pfizer, Protagonist, Roivant, and Takeda.
A version of this article appeared on Medscape.com.
, suggesting this approach will not harm the fetus.
The guidelines also recommend that all women with IBD receive preconception counseling and be followed as high-risk pregnancies.
“Management of chronic illness in pregnant women has always been defined by fear of harming the fetus,” said Uma Mahadevan, MD, AGAF, director of the Colitis and Crohn’s Disease Center at the University of California San Francisco and chair of the Global Consensus Consortium that developed the guidelines.
As a result, pregnant women are excluded from clinical trials of experimental therapies for IBD. And when a new therapy achieves regulatory approval, there are no human pregnancy safety data, only animal data. To fill this gap, the PIANO study, of which Mahadevan is principal investigator, looked at the safety of IBD medications in pregnancy and short- and long-term outcomes of the children.
“With our ongoing work in pregnancy in the patient with IBD, we realized that inflammation in the mother is the leading cause of poor outcome for the infant,” she told GI & Hepatology News.
“We also have a better understanding of placental transfer of biologic agents” and the lack of exposure to the fetus during the first trimester, “a key period of organogenesis,” she added.
Final recommendations were published simultaneously in six international journals, namely, Clinical Gastroenterology and Hepatology, American Journal of Gastroenterology, GUT, Inflammatory Bowel Diseases, Journal of Crohn’s and Colitis, and Alimentary Pharmacology and Therapeutics.
Surprising, Novel Findings
Limited provider knowledge led to varied practices in caring for women with IBD who become pregnant, according to the consensus authors. Practices are affected by local dogma, available resources, individual interpretation of the literature, and fear of harming the fetus.
“The variations in guidelines by different societies and countries reflect this and lead to confusion for physicians and patients alike,” the authors of the guidelines wrote.
Therefore, the Global Consensus Consortium — a group of 39 IBD experts, including teratologists and maternal fetal medicine specialists and seven patient advocates from six continents — convened to review and assess current data and come to an agreement on best practices. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used when sufficient published data were available, and the Research and Development process when expert opinion was needed to guide consistent practice.
“Some of the findings were expected, but others were novel,” said Mahadevan.
Recommendations that might surprise clinicians include GRADE statement 9, which suggests that pregnant women with IBD take low-dose aspirin by 12 to 16 weeks’ gestation to prevent preterm preeclampsia. “This is based on the ASPRE study, showing that women at risk of preeclampsia can lower their risk by taking low-dose aspirin,” with no risk for flare, Mahadevan said.
In addition, GRADE statements 17-20 recommend/suggest that women continue their biologic throughout pregnancy without stopping. “North America has always recommended continuing during the third trimester, while Europe only recently has come to this,” Mahadevan said. “However, there was always some looseness about stopping at week X, Y, or Z. Now, we do recommend continuing the dose on schedule with no holding.”
Continuing medications considered low risk for use during pregnancy, such as 5-amino salicylic acids, sulfasalazine, thiopurines, and all monoclonal antibodies during preconception, pregnancy, and lactation, was also recommended.
However, small-molecule drugs such as S1P receptor molecules and JAK inhibitors should be avoided for at least 1 month, and in some cases for 3 months prior to attempting conception, unless there is no alternative for the health of the mother. They should also be avoided during lactation.
Grade statement 33, which suggests that live rotavirus vaccine may be provided in children with in utero exposure to biologics, is also new, Mahadevan noted. “All prior recommendations were that no live vaccine should be given in the first 6 months or longer if infants were exposed to biologics in utero, but based on a prospective Canadian study, there is no harm when given to these infants.”
Another novel recommendation is that women with IBD on any monoclonal antibodies, including newer interleukin-23s, may breastfeed even though there are not clinical trial data at this point. The recommendation to continue them through pregnancy and lactation is based on placental physiology, as well as on the physiology of monoclonal antibody transfer in breast milk, according to the consortium.
Furthermore, the authors noted, there was no increase in infant infections at 4 months or 12 months if they were exposed to a biologic or thiopurine (or both) during pregnancy.
Overall, the consortium recommended that all pregnancies for women with IBD be considered as “high risk” for complications. This is due to the fact that many parts of the world, including the US, are “resource-limited,” Mahadevan explained. Since maternal fetal medicine specialists are not widely available, the consortium suggested all these patients be followed with increased monitoring and surveillance based on available resources.
In addition to the guidelines, patient videos in seven languages, a professional slide deck in English and Spanish, and a video on the global consensus are all available at https://pianostudy.org/.
This study was funded by The Leona B. and Harry H. Helmsley Charitable Trust.
Mahadevan reported being a consultant for AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Celltrion, Enveda, Gilead, Janssen, Lilly, Merck, Pfizer, Protagonist, Roivant, and Takeda.
A version of this article appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Intestinal Methanogen Overgrowth Fosters More Constipation, Less Diarrhea
, according to a systematic review and meta-analysis published in Clinical Gastroenterology and Hepatology.
“The distinct phenotype of patients with IMO should be incorporated in patient-reported outcome measures and further correlated with mechanistic microbiome studies,” wrote investigators led by gastroenterologist Ali Rezaie, MD, MSc, medical director of the GI Motility Program at Cedars-Sinai Medical Center and director of biotechnology in the center’s Medically Associated Science and Technology (MAST) Program. Recognizing specific GI symptom profiles can improve diagnosis and treatment strategies, facilitating further clinical trials and targeted microbiome studies to optimize patient care.
Excessive luminal loads of methanogenic archaea – archaea being bacteria-like prokaryotes and one of the main three domains of the tree of life – have been implicated in the pathophysiology of various diseases, including constipation.
The Study
To elucidate the phenotypical presentation of IMO in patients, Rezaie’s group compared the prevalence and severity of gastrointestinal (GI) symptoms in individuals who had IMO with those who did not have IMO. IMO was based on excess levels of this gaseous GI byproduct in exhaled breath tests.
Searching electronic databases from inception to September 2023, the researchers identified 19 eligible studies from diverse geographical regions with 1293 IMO patients and 3208 controls. Eleven studies were performed in the United States; the other studies were conducted in France (n = 2), India (n = 2), New Zealand (n = 1), South Korea (n = 1), Italy (n = 1), and the United Kingdom (n = 1). Thirteen studies were of high quality, as defined by a Newcastle-Ottawa Assessment Scale score of 6.
Patients with IMO were found to exhibit a range of GI symptoms, including bloating (78%), constipation (51%), diarrhea (33%), abdominal pain (65%), nausea (30%), and flatulence (56%).
In other findings:
- Patients with IMO had a significantly higher prevalence of constipation vs controls: 47% vs 38% (odds ratio [OR], 2.04, 95% confidence interval [CI], 1.48-2.83, P < .0001).
- They had a lower prevalence of diarrhea: 37% vs 52% (OR .58, 95% CI, .37-.90, P = .01); and nausea: 32% vs 45%; (OR, .75; 95% CI, .60-.94, P = .01).
- Patients with IMO had more severe constipation: standard mean deviation [SMD], .77 (95% CI, .11-1.43, P = .02) and a lower severity of diarrhea: SMD, –.71 (95% CI, –1.39 to –.03, P = .04). Significant heterogeneity of effect, however, was detected.
- Constipation was more prevalent in IMO diagnosed with the lactulose breath test and the glucose breath test and constipation was particularly prevalent in Europe and the United States.
Mechanism of Action
The findings on constipation and diarrhea corroborate methane’s slowing physiologic effects on motility, the authors noted. It has been consistently found to delay gut transit, both small bowel and colonic transit.
Mechanistically, methane reduces small intestinal peristaltic velocity while augmenting non-propagating contraction amplitude, suggesting that reduction of intestinal transit time is mediated through promotion of non-propulsive contractions.
“This study further consolidates methane’s causal role in constipation and paves the way to establish validated disease-specific patient-reported outcomes,” Rezaie and associates wrote, calling for longitudinal and mechanistic studies assessing the archaeome in order to advance understanding of IMO.
This study was funded in part by Nancy Stark and Stanley Lezman in support of the MAST Program’s Innovation Project at Cedars-Sinai.
Rezaie serves as a consultant/speaker for Bausch Health. Cedars-Sinai Medical Center has a licensing agreement with Gemelli Biotech, in which Rezaie and coauthor Pimentel have equity. They also hold equity in Good LIFE. Pimentel consults for and has received grant support from Bausch Health.
, according to a systematic review and meta-analysis published in Clinical Gastroenterology and Hepatology.
“The distinct phenotype of patients with IMO should be incorporated in patient-reported outcome measures and further correlated with mechanistic microbiome studies,” wrote investigators led by gastroenterologist Ali Rezaie, MD, MSc, medical director of the GI Motility Program at Cedars-Sinai Medical Center and director of biotechnology in the center’s Medically Associated Science and Technology (MAST) Program. Recognizing specific GI symptom profiles can improve diagnosis and treatment strategies, facilitating further clinical trials and targeted microbiome studies to optimize patient care.
Excessive luminal loads of methanogenic archaea – archaea being bacteria-like prokaryotes and one of the main three domains of the tree of life – have been implicated in the pathophysiology of various diseases, including constipation.
The Study
To elucidate the phenotypical presentation of IMO in patients, Rezaie’s group compared the prevalence and severity of gastrointestinal (GI) symptoms in individuals who had IMO with those who did not have IMO. IMO was based on excess levels of this gaseous GI byproduct in exhaled breath tests.
Searching electronic databases from inception to September 2023, the researchers identified 19 eligible studies from diverse geographical regions with 1293 IMO patients and 3208 controls. Eleven studies were performed in the United States; the other studies were conducted in France (n = 2), India (n = 2), New Zealand (n = 1), South Korea (n = 1), Italy (n = 1), and the United Kingdom (n = 1). Thirteen studies were of high quality, as defined by a Newcastle-Ottawa Assessment Scale score of 6.
Patients with IMO were found to exhibit a range of GI symptoms, including bloating (78%), constipation (51%), diarrhea (33%), abdominal pain (65%), nausea (30%), and flatulence (56%).
In other findings:
- Patients with IMO had a significantly higher prevalence of constipation vs controls: 47% vs 38% (odds ratio [OR], 2.04, 95% confidence interval [CI], 1.48-2.83, P < .0001).
- They had a lower prevalence of diarrhea: 37% vs 52% (OR .58, 95% CI, .37-.90, P = .01); and nausea: 32% vs 45%; (OR, .75; 95% CI, .60-.94, P = .01).
- Patients with IMO had more severe constipation: standard mean deviation [SMD], .77 (95% CI, .11-1.43, P = .02) and a lower severity of diarrhea: SMD, –.71 (95% CI, –1.39 to –.03, P = .04). Significant heterogeneity of effect, however, was detected.
- Constipation was more prevalent in IMO diagnosed with the lactulose breath test and the glucose breath test and constipation was particularly prevalent in Europe and the United States.
Mechanism of Action
The findings on constipation and diarrhea corroborate methane’s slowing physiologic effects on motility, the authors noted. It has been consistently found to delay gut transit, both small bowel and colonic transit.
Mechanistically, methane reduces small intestinal peristaltic velocity while augmenting non-propagating contraction amplitude, suggesting that reduction of intestinal transit time is mediated through promotion of non-propulsive contractions.
“This study further consolidates methane’s causal role in constipation and paves the way to establish validated disease-specific patient-reported outcomes,” Rezaie and associates wrote, calling for longitudinal and mechanistic studies assessing the archaeome in order to advance understanding of IMO.
This study was funded in part by Nancy Stark and Stanley Lezman in support of the MAST Program’s Innovation Project at Cedars-Sinai.
Rezaie serves as a consultant/speaker for Bausch Health. Cedars-Sinai Medical Center has a licensing agreement with Gemelli Biotech, in which Rezaie and coauthor Pimentel have equity. They also hold equity in Good LIFE. Pimentel consults for and has received grant support from Bausch Health.
, according to a systematic review and meta-analysis published in Clinical Gastroenterology and Hepatology.
“The distinct phenotype of patients with IMO should be incorporated in patient-reported outcome measures and further correlated with mechanistic microbiome studies,” wrote investigators led by gastroenterologist Ali Rezaie, MD, MSc, medical director of the GI Motility Program at Cedars-Sinai Medical Center and director of biotechnology in the center’s Medically Associated Science and Technology (MAST) Program. Recognizing specific GI symptom profiles can improve diagnosis and treatment strategies, facilitating further clinical trials and targeted microbiome studies to optimize patient care.
Excessive luminal loads of methanogenic archaea – archaea being bacteria-like prokaryotes and one of the main three domains of the tree of life – have been implicated in the pathophysiology of various diseases, including constipation.
The Study
To elucidate the phenotypical presentation of IMO in patients, Rezaie’s group compared the prevalence and severity of gastrointestinal (GI) symptoms in individuals who had IMO with those who did not have IMO. IMO was based on excess levels of this gaseous GI byproduct in exhaled breath tests.
Searching electronic databases from inception to September 2023, the researchers identified 19 eligible studies from diverse geographical regions with 1293 IMO patients and 3208 controls. Eleven studies were performed in the United States; the other studies were conducted in France (n = 2), India (n = 2), New Zealand (n = 1), South Korea (n = 1), Italy (n = 1), and the United Kingdom (n = 1). Thirteen studies were of high quality, as defined by a Newcastle-Ottawa Assessment Scale score of 6.
Patients with IMO were found to exhibit a range of GI symptoms, including bloating (78%), constipation (51%), diarrhea (33%), abdominal pain (65%), nausea (30%), and flatulence (56%).
In other findings:
- Patients with IMO had a significantly higher prevalence of constipation vs controls: 47% vs 38% (odds ratio [OR], 2.04, 95% confidence interval [CI], 1.48-2.83, P < .0001).
- They had a lower prevalence of diarrhea: 37% vs 52% (OR .58, 95% CI, .37-.90, P = .01); and nausea: 32% vs 45%; (OR, .75; 95% CI, .60-.94, P = .01).
- Patients with IMO had more severe constipation: standard mean deviation [SMD], .77 (95% CI, .11-1.43, P = .02) and a lower severity of diarrhea: SMD, –.71 (95% CI, –1.39 to –.03, P = .04). Significant heterogeneity of effect, however, was detected.
- Constipation was more prevalent in IMO diagnosed with the lactulose breath test and the glucose breath test and constipation was particularly prevalent in Europe and the United States.
Mechanism of Action
The findings on constipation and diarrhea corroborate methane’s slowing physiologic effects on motility, the authors noted. It has been consistently found to delay gut transit, both small bowel and colonic transit.
Mechanistically, methane reduces small intestinal peristaltic velocity while augmenting non-propagating contraction amplitude, suggesting that reduction of intestinal transit time is mediated through promotion of non-propulsive contractions.
“This study further consolidates methane’s causal role in constipation and paves the way to establish validated disease-specific patient-reported outcomes,” Rezaie and associates wrote, calling for longitudinal and mechanistic studies assessing the archaeome in order to advance understanding of IMO.
This study was funded in part by Nancy Stark and Stanley Lezman in support of the MAST Program’s Innovation Project at Cedars-Sinai.
Rezaie serves as a consultant/speaker for Bausch Health. Cedars-Sinai Medical Center has a licensing agreement with Gemelli Biotech, in which Rezaie and coauthor Pimentel have equity. They also hold equity in Good LIFE. Pimentel consults for and has received grant support from Bausch Health.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY