GI and Hepatology News

Many patients with Crohn’s disease (CD) have a heightened immune response to flagellins expressed by commensal gut bacteria Lachnospiraceae, with seroreactivity appearing up to 5 years prior to development of Crohn’s complications, according to investigators.

These findings suggest that the flagellin cytometric bead array used in the present study could serve as a simple diagnostic and prognostic tool for patients with CD, and point to a new therapeutic target, lead author Qing Zhao, MD, PhD, of the University of Alabama at Birmingham, and colleagues reported.

Qing Zhao

Previously, Zhao and colleagues found that about 30% of patients with CD had elevated IgG responses to multiple Lachnospiraceae flagellins, and stronger reactivity was associated with higher flagellin-specific CD4+ T cells in circulation.

“In this study, we aimed to identify immunodominant B cell peptide epitopes shared among Lachnospiraceae bacterial flagellins in patients with CD and to correlate this immune reactivity with the clinical disease course,” the investigators wrote in Gastroenterology.

To this end, the investigators analyzed serum samples from adult CD patients, pediatric CD patients, and healthy infants without inflammatory bowel disease, with data derived from multiple sources. Adult patients with CD were part of a regional cohort recruited at the University of Alabama at Birmingham, while pediatric patients with CD came from the RISK Stratification Study, a multisite cohort study across the United States and Canada. Samples from healthy infants were collected from three diverse geographic locations: Uganda, Sweden, and the United States, providing a broad comparison of immune responses to Lachnospiraceae flagellin across populations.

Samples were analyzed via two main methods: a flagellin peptide microarray and a cytometric bead array. The microarray, comprising sequential Lachnospiraceae-derived peptides, enabled identification of IgG responses specific to individual bacterial peptides. The cytometric bead array allowed for multiplexed detection of IgG, IgA, and IgM antibodies to these peptides, quantifying immune reactivity and enabling correlation with clinical disease data.

This approach revealed that nearly half of patients with CD — both adults and children — had a strong IgG immune response targeting a specific bacterial peptide in the Lachnospiraceae flagellin hinge region. This response was linked to an increased risk of disease complications over time, suggesting the peptide’s potential as a biomarker for CD severity and progression, according to the investigators.

Of note, healthy infants also exhibited an elevated IgG response to the same bacterial peptide at around 1 year of age, but this response declined as they grew older, in contrast to its persistence in CD patients. This difference points to a possible failure in immune tolerance in CD, where the natural immune response to gut bacteria in infancy may become dysregulated, Zhao and colleagues explained.

“The flagellin cytometric bead array used in this study holds potential for a simplified yet robust diagnostic and prognostic assay for Crohn’s disease,” they concluded. “Given that reactivity to the dominant flagellin epitope is strongly associated with the development of disease complications, this technique may also assist in identifying patients with Crohn’s disease who would benefit from early therapy.”

Zhao and colleagues also called for future studies to characterize the role of flagellin hinge peptide–specific IgG antibodies in CD pathogenesis, and to explore the hinge peptide as a potential therapeutic target.The study was supported by a Synergy Award from the Kenneth Rainin Foundation, a Career Development Award from the Crohn’s and Colitis Foundation, and grants from the Department of Veterans Affairs, National Institute of Allergy and Infectious Diseases, National Institutes of Health, and National Institute of Diabetes and Digestive and Kidney Diseases. One coauthor and the University of Alabama at Birmingham hold a patent on Lachnospiraceae A4 Fla2, licensed for clinical application by Prometheus Laboratories. Four study coauthors have filed a patent for the flagellin peptide cytometric bead array. One coauthor serves as the founder and chief scientific officer of ImmPrev Bio, a company developing an antigen-directed immunotherapy for Crohn’s disease.

Many patients with Crohn’s disease (CD) have a heightened immune response to flagellins expressed by commensal gut bacteria Lachnospiraceae, with seroreactivity appearing up to 5 years prior to development of Crohn’s complications, according to investigators.

These findings suggest that the flagellin cytometric bead array used in the present study could serve as a simple diagnostic and prognostic tool for patients with CD, and point to a new therapeutic target, lead author Qing Zhao, MD, PhD, of the University of Alabama at Birmingham, and colleagues reported.

Qing Zhao

Previously, Zhao and colleagues found that about 30% of patients with CD had elevated IgG responses to multiple Lachnospiraceae flagellins, and stronger reactivity was associated with higher flagellin-specific CD4+ T cells in circulation.

“In this study, we aimed to identify immunodominant B cell peptide epitopes shared among Lachnospiraceae bacterial flagellins in patients with CD and to correlate this immune reactivity with the clinical disease course,” the investigators wrote in Gastroenterology.

To this end, the investigators analyzed serum samples from adult CD patients, pediatric CD patients, and healthy infants without inflammatory bowel disease, with data derived from multiple sources. Adult patients with CD were part of a regional cohort recruited at the University of Alabama at Birmingham, while pediatric patients with CD came from the RISK Stratification Study, a multisite cohort study across the United States and Canada. Samples from healthy infants were collected from three diverse geographic locations: Uganda, Sweden, and the United States, providing a broad comparison of immune responses to Lachnospiraceae flagellin across populations.

Samples were analyzed via two main methods: a flagellin peptide microarray and a cytometric bead array. The microarray, comprising sequential Lachnospiraceae-derived peptides, enabled identification of IgG responses specific to individual bacterial peptides. The cytometric bead array allowed for multiplexed detection of IgG, IgA, and IgM antibodies to these peptides, quantifying immune reactivity and enabling correlation with clinical disease data.

This approach revealed that nearly half of patients with CD — both adults and children — had a strong IgG immune response targeting a specific bacterial peptide in the Lachnospiraceae flagellin hinge region. This response was linked to an increased risk of disease complications over time, suggesting the peptide’s potential as a biomarker for CD severity and progression, according to the investigators.

Of note, healthy infants also exhibited an elevated IgG response to the same bacterial peptide at around 1 year of age, but this response declined as they grew older, in contrast to its persistence in CD patients. This difference points to a possible failure in immune tolerance in CD, where the natural immune response to gut bacteria in infancy may become dysregulated, Zhao and colleagues explained.

“The flagellin cytometric bead array used in this study holds potential for a simplified yet robust diagnostic and prognostic assay for Crohn’s disease,” they concluded. “Given that reactivity to the dominant flagellin epitope is strongly associated with the development of disease complications, this technique may also assist in identifying patients with Crohn’s disease who would benefit from early therapy.”

Zhao and colleagues also called for future studies to characterize the role of flagellin hinge peptide–specific IgG antibodies in CD pathogenesis, and to explore the hinge peptide as a potential therapeutic target.The study was supported by a Synergy Award from the Kenneth Rainin Foundation, a Career Development Award from the Crohn’s and Colitis Foundation, and grants from the Department of Veterans Affairs, National Institute of Allergy and Infectious Diseases, National Institutes of Health, and National Institute of Diabetes and Digestive and Kidney Diseases. One coauthor and the University of Alabama at Birmingham hold a patent on Lachnospiraceae A4 Fla2, licensed for clinical application by Prometheus Laboratories. Four study coauthors have filed a patent for the flagellin peptide cytometric bead array. One coauthor serves as the founder and chief scientific officer of ImmPrev Bio, a company developing an antigen-directed immunotherapy for Crohn’s disease.

Many patients with Crohn’s disease (CD) have a heightened immune response to flagellins expressed by commensal gut bacteria Lachnospiraceae, with seroreactivity appearing up to 5 years prior to development of Crohn’s complications, according to investigators.

These findings suggest that the flagellin cytometric bead array used in the present study could serve as a simple diagnostic and prognostic tool for patients with CD, and point to a new therapeutic target, lead author Qing Zhao, MD, PhD, of the University of Alabama at Birmingham, and colleagues reported.

Qing Zhao

Previously, Zhao and colleagues found that about 30% of patients with CD had elevated IgG responses to multiple Lachnospiraceae flagellins, and stronger reactivity was associated with higher flagellin-specific CD4+ T cells in circulation.

“In this study, we aimed to identify immunodominant B cell peptide epitopes shared among Lachnospiraceae bacterial flagellins in patients with CD and to correlate this immune reactivity with the clinical disease course,” the investigators wrote in Gastroenterology.

To this end, the investigators analyzed serum samples from adult CD patients, pediatric CD patients, and healthy infants without inflammatory bowel disease, with data derived from multiple sources. Adult patients with CD were part of a regional cohort recruited at the University of Alabama at Birmingham, while pediatric patients with CD came from the RISK Stratification Study, a multisite cohort study across the United States and Canada. Samples from healthy infants were collected from three diverse geographic locations: Uganda, Sweden, and the United States, providing a broad comparison of immune responses to Lachnospiraceae flagellin across populations.

Samples were analyzed via two main methods: a flagellin peptide microarray and a cytometric bead array. The microarray, comprising sequential Lachnospiraceae-derived peptides, enabled identification of IgG responses specific to individual bacterial peptides. The cytometric bead array allowed for multiplexed detection of IgG, IgA, and IgM antibodies to these peptides, quantifying immune reactivity and enabling correlation with clinical disease data.

This approach revealed that nearly half of patients with CD — both adults and children — had a strong IgG immune response targeting a specific bacterial peptide in the Lachnospiraceae flagellin hinge region. This response was linked to an increased risk of disease complications over time, suggesting the peptide’s potential as a biomarker for CD severity and progression, according to the investigators.

Of note, healthy infants also exhibited an elevated IgG response to the same bacterial peptide at around 1 year of age, but this response declined as they grew older, in contrast to its persistence in CD patients. This difference points to a possible failure in immune tolerance in CD, where the natural immune response to gut bacteria in infancy may become dysregulated, Zhao and colleagues explained.

“The flagellin cytometric bead array used in this study holds potential for a simplified yet robust diagnostic and prognostic assay for Crohn’s disease,” they concluded. “Given that reactivity to the dominant flagellin epitope is strongly associated with the development of disease complications, this technique may also assist in identifying patients with Crohn’s disease who would benefit from early therapy.”

Zhao and colleagues also called for future studies to characterize the role of flagellin hinge peptide–specific IgG antibodies in CD pathogenesis, and to explore the hinge peptide as a potential therapeutic target.The study was supported by a Synergy Award from the Kenneth Rainin Foundation, a Career Development Award from the Crohn’s and Colitis Foundation, and grants from the Department of Veterans Affairs, National Institute of Allergy and Infectious Diseases, National Institutes of Health, and National Institute of Diabetes and Digestive and Kidney Diseases. One coauthor and the University of Alabama at Birmingham hold a patent on Lachnospiraceae A4 Fla2, licensed for clinical application by Prometheus Laboratories. Four study coauthors have filed a patent for the flagellin peptide cytometric bead array. One coauthor serves as the founder and chief scientific officer of ImmPrev Bio, a company developing an antigen-directed immunotherapy for Crohn’s disease.

Semaglutide use is associated with an increased risk of retained solid gastric contents, but colonoscopy prep appears to mitigate this issue, according to investigators.

These findings suggest that patients taking GLP-1 receptor agonists (GLP-1RAs) may benefit from a 24-hour liquid fast before anesthetic procedures without the need for a medication hold, reported lead author Haarika Korlipara, MD, of NewYork–Presbyterian/Weill Cornell Medical Center, New York, and colleagues.

“[T]he effects of delayed gastric emptying in patients on long-acting GLP-1RAs are clinically important in the management of anesthetized patients, who may develop periprocedural complications in the setting of retained solid gastric contents,” the investigators wrote in Techniques and Innovations in Gastrointestinal Endoscopy.

NewYork-Presbyterian/Weill Cornell Medical Center

The researchers retrospectively analyzed clinical data from 1,212 patients undergoing upper endoscopy at a tertiary care center. Among them, 602 were on semaglutide for more than four weeks, while 610 were controls not taking the medication.

The primary outcome was the presence of retained solid gastric contents. Secondary outcomes included the need for intubation, early procedure termination, and recommendations for repeat endoscopy.

Semaglutide use was an independent predictor of retained solid gastric contents (odds ratio [OR], 4.74; 95% CI, 2.40-9.35; P less than .0001). Multivariable propensity-matched analysis showed a 6% absolute increase in retained gastric contents in the semaglutide group compared to controls (P less than .0001).

This increase appeared clinically relevant, as semaglutide use was associated with a higher rate of early procedure termination (OR, 3.09; P = 0.02) and recommendations for repeat endoscopies (OR, 3.61; P = 0.02), “indicating the degree of retained solid gastric contents was enough to limit the intended gastric mucosal examination,” the investigators wrote.

However, patients who underwent same-day colonoscopy, which included a 24-hour clear liquid fast leading up to the procedure, were less likely to have retained gastric contents (OR, 0.41; 95% CI, 0.23-0.73; P = 0.003), suggesting that extended fasting protocols may mitigate the risk of procedural complications.

“Patients with a history of gastroparesis are often advised to stop ingesting solid foods and maintain a clear liquid diet for a longer period than standard ASA guidance before anesthetized procedures,” Dr. Korlipara and colleagues wrote. “In our opinion, this recommendation should be considered in patients on long-term GLP-1RA therapy, in response to the findings reported in this study and others about the protective effects of a 24-hour liquid fast.”

Point-of-care gastric ultrasound may also be considered to evaluate patients at higher risk of retained stomach contents, they added, especially in patients with additional risk factors for delayed gastric emptying.

“Previously published data have linked prolonged gastric emptying delays in patients chronically using these medications,” they wrote. “Considering the effect on blood sugar and associated procedural risk, especially in patients taking this medication for diabetes management, more studies are warranted to determine the effect of medication on periprocedural complications and recommend repeat evaluation.”

After this study was released, new clinical guidance on the use of GLP-1RAs before surgery was co-published by AGA and four other societies. The guidance notes that, in most cases, patients can continue to take GLP-1RAs, but individual risk factors for complications should be assessed prior to surgery. The guidance cautions that patients at high risk for significant GI side effects should follow a liquid diet for 24 hours before a procedure and the anesthesia plan be adjusted accordingly. In rare cases, the procedure should be delayed.

Dr. Korlipara disclosed no conflicts of interest.

Semaglutide use is associated with an increased risk of retained solid gastric contents, but colonoscopy prep appears to mitigate this issue, according to investigators.

These findings suggest that patients taking GLP-1 receptor agonists (GLP-1RAs) may benefit from a 24-hour liquid fast before anesthetic procedures without the need for a medication hold, reported lead author Haarika Korlipara, MD, of NewYork–Presbyterian/Weill Cornell Medical Center, New York, and colleagues.

“[T]he effects of delayed gastric emptying in patients on long-acting GLP-1RAs are clinically important in the management of anesthetized patients, who may develop periprocedural complications in the setting of retained solid gastric contents,” the investigators wrote in Techniques and Innovations in Gastrointestinal Endoscopy.

NewYork-Presbyterian/Weill Cornell Medical Center

The researchers retrospectively analyzed clinical data from 1,212 patients undergoing upper endoscopy at a tertiary care center. Among them, 602 were on semaglutide for more than four weeks, while 610 were controls not taking the medication.

The primary outcome was the presence of retained solid gastric contents. Secondary outcomes included the need for intubation, early procedure termination, and recommendations for repeat endoscopy.

Semaglutide use was an independent predictor of retained solid gastric contents (odds ratio [OR], 4.74; 95% CI, 2.40-9.35; P less than .0001). Multivariable propensity-matched analysis showed a 6% absolute increase in retained gastric contents in the semaglutide group compared to controls (P less than .0001).

This increase appeared clinically relevant, as semaglutide use was associated with a higher rate of early procedure termination (OR, 3.09; P = 0.02) and recommendations for repeat endoscopies (OR, 3.61; P = 0.02), “indicating the degree of retained solid gastric contents was enough to limit the intended gastric mucosal examination,” the investigators wrote.

However, patients who underwent same-day colonoscopy, which included a 24-hour clear liquid fast leading up to the procedure, were less likely to have retained gastric contents (OR, 0.41; 95% CI, 0.23-0.73; P = 0.003), suggesting that extended fasting protocols may mitigate the risk of procedural complications.

“Patients with a history of gastroparesis are often advised to stop ingesting solid foods and maintain a clear liquid diet for a longer period than standard ASA guidance before anesthetized procedures,” Dr. Korlipara and colleagues wrote. “In our opinion, this recommendation should be considered in patients on long-term GLP-1RA therapy, in response to the findings reported in this study and others about the protective effects of a 24-hour liquid fast.”

Point-of-care gastric ultrasound may also be considered to evaluate patients at higher risk of retained stomach contents, they added, especially in patients with additional risk factors for delayed gastric emptying.

“Previously published data have linked prolonged gastric emptying delays in patients chronically using these medications,” they wrote. “Considering the effect on blood sugar and associated procedural risk, especially in patients taking this medication for diabetes management, more studies are warranted to determine the effect of medication on periprocedural complications and recommend repeat evaluation.”

After this study was released, new clinical guidance on the use of GLP-1RAs before surgery was co-published by AGA and four other societies. The guidance notes that, in most cases, patients can continue to take GLP-1RAs, but individual risk factors for complications should be assessed prior to surgery. The guidance cautions that patients at high risk for significant GI side effects should follow a liquid diet for 24 hours before a procedure and the anesthesia plan be adjusted accordingly. In rare cases, the procedure should be delayed.

Dr. Korlipara disclosed no conflicts of interest.

Semaglutide use is associated with an increased risk of retained solid gastric contents, but colonoscopy prep appears to mitigate this issue, according to investigators.

These findings suggest that patients taking GLP-1 receptor agonists (GLP-1RAs) may benefit from a 24-hour liquid fast before anesthetic procedures without the need for a medication hold, reported lead author Haarika Korlipara, MD, of NewYork–Presbyterian/Weill Cornell Medical Center, New York, and colleagues.

“[T]he effects of delayed gastric emptying in patients on long-acting GLP-1RAs are clinically important in the management of anesthetized patients, who may develop periprocedural complications in the setting of retained solid gastric contents,” the investigators wrote in Techniques and Innovations in Gastrointestinal Endoscopy.

NewYork-Presbyterian/Weill Cornell Medical Center

The researchers retrospectively analyzed clinical data from 1,212 patients undergoing upper endoscopy at a tertiary care center. Among them, 602 were on semaglutide for more than four weeks, while 610 were controls not taking the medication.

The primary outcome was the presence of retained solid gastric contents. Secondary outcomes included the need for intubation, early procedure termination, and recommendations for repeat endoscopy.

Semaglutide use was an independent predictor of retained solid gastric contents (odds ratio [OR], 4.74; 95% CI, 2.40-9.35; P less than .0001). Multivariable propensity-matched analysis showed a 6% absolute increase in retained gastric contents in the semaglutide group compared to controls (P less than .0001).

This increase appeared clinically relevant, as semaglutide use was associated with a higher rate of early procedure termination (OR, 3.09; P = 0.02) and recommendations for repeat endoscopies (OR, 3.61; P = 0.02), “indicating the degree of retained solid gastric contents was enough to limit the intended gastric mucosal examination,” the investigators wrote.

However, patients who underwent same-day colonoscopy, which included a 24-hour clear liquid fast leading up to the procedure, were less likely to have retained gastric contents (OR, 0.41; 95% CI, 0.23-0.73; P = 0.003), suggesting that extended fasting protocols may mitigate the risk of procedural complications.

“Patients with a history of gastroparesis are often advised to stop ingesting solid foods and maintain a clear liquid diet for a longer period than standard ASA guidance before anesthetized procedures,” Dr. Korlipara and colleagues wrote. “In our opinion, this recommendation should be considered in patients on long-term GLP-1RA therapy, in response to the findings reported in this study and others about the protective effects of a 24-hour liquid fast.”

Point-of-care gastric ultrasound may also be considered to evaluate patients at higher risk of retained stomach contents, they added, especially in patients with additional risk factors for delayed gastric emptying.

“Previously published data have linked prolonged gastric emptying delays in patients chronically using these medications,” they wrote. “Considering the effect on blood sugar and associated procedural risk, especially in patients taking this medication for diabetes management, more studies are warranted to determine the effect of medication on periprocedural complications and recommend repeat evaluation.”

After this study was released, new clinical guidance on the use of GLP-1RAs before surgery was co-published by AGA and four other societies. The guidance notes that, in most cases, patients can continue to take GLP-1RAs, but individual risk factors for complications should be assessed prior to surgery. The guidance cautions that patients at high risk for significant GI side effects should follow a liquid diet for 24 hours before a procedure and the anesthesia plan be adjusted accordingly. In rare cases, the procedure should be delayed.

Dr. Korlipara disclosed no conflicts of interest.

The majority of patients may safely take glucagon-like peptide 1 receptor agonists (GLP-1 RAs) before elective surgery and gastrointestinal endoscopies, according to updated guidance from five medical societies.

The new guidance, contrasting with earlier recommendations, says these incrementally used agents can be taken up until the day of surgery, but patients are advised to follow a liquid diet for 24 hours before the procedure. The decision to proceed with endoscopy and other procedures should be based on shared decision-making with the patient and interdisciplinary care teams in conjunction with minimization of the aspiration risk from delayed gastric emptying, the guidance stresses.

The five endorsing organizations are the American Society for Metabolic and Bariatric Surgery, American Society of Anesthesiologists (ASA), American Gastroenterological Association, International Society of Perioperative Care of Patients with Obesity, and Society of American Gastrointestinal and Endoscopic Surgeons. The societies emphasize that the statement is intended as guidance only and is not an evidence-based formal guideline.

GLP-1 RAs are known to delay gastric emptying, raising concerns about regurgitation, aspiration, and airway compromise during anesthesia. Rare serious adverse events have also been observed, prompting the ASA in 2023 to recommend holding these agents for 1 week for the injectable form and 1 day for the oral form before all procedures requiring anesthesia. 

 

University of Michigan

That abundance of caution, however, had negative impacts of its own. “This guidance has led to cancellations and postponements of many endoscopic and surgical procedures or required patients to undergo general anesthesia who may otherwise have had their procedures performed under moderate sedation,” said guidance coauthor Allison R. Schulman, MD, MPH, an associate professor of medicine and surgery and chief of endoscopy at the University of Michigan in Ann Arbor. “Nearly all institutions have been forced to revise preprocedural protocols, despite a lack of high-level evidence to suggest that these adjustments are necessary.”

“Studies have yielded mixed results as to whether patients on GLP-1s are at increased risk of these events, and the limited data available are inconsistent,” Schulman said. “As a result, there are inconsistencies in the recommendations from various societies leading to growing uncertainty with proceduralists on how to provide safe, effective, and timely procedural care to patients taking GLP-1 RAs.”

The new joint-society guidance may alleviate some of the uncertainty. Among the recommendations:

• Continuing GLP-1 RAs in the perioperative period should be based on shared decision-making with the patient and all care teams balancing the metabolic need for the GLP-1 RA with individual patient risk.
• Certain variables may increase the risk for delayed gastric emptying and aspiration with the periprocedural use of GLP-1 RAs: escalation phase — This phase vs the maintenance phase is associated with a higher risk for delayed gastric emptying; higher dose — the higher the dose, the greater the risk for gastrointestinal (GI) side effects; weekly dosing — GI side effects are more common with weekly vs daily formulations; presence of GI symptoms — nausea, vomiting, abdominal pain, dyspepsia, and constipation may suggest delayed gastric emptying; and medical problems beyond GLP-1 RA indications with GI effects — assess for such conditions as bowel dysmotility, gastroparesis, and Parkinson’s disease.
• Risk factors should be assessed in advance to allow sufficient time to adjust preoperative care, including diet modification and medication bridging if GLP-1 RA cessation is deemed advisable.
• If retained gastric contents are a concern on the day of a procedure, point-of-care gastric ultrasound could be used to assess aspiration risk, resources permitting.
• The aspiration risk from delayed gastric emptying should be minimized by preoperative diet modification and/or altering the anesthesia plan to consider rapid sequence induction of general anesthesia for tracheal intubation. A 24-hour preoperative liquid diet, as before colonoscopy and bariatric surgery, can be utilized when delayed gastric emptying is a concern.
• When concern about retained gastric contents exists on procedure day, providers should engage patients in a shared decision-making model and consider the benefits and risks of rapid-sequence induction of general anesthesia for tracheal intubation to minimize aspiration risk vs procedure cancellation.

“Safe continuation of surgery and gastrointestinal endoscopy, and prevention of procedure cancellation, for patients on GLP-1 RAs can be prioritized following the recommendations above, as would occur for other patient populations with gastroparesis,” the guidance panel wrote.

 

Digestive Health Center of Huntington

Commenting on the statement but not involved in it, David B. Purow, MD, managing director of the Digestive Health Center at Northwell Health/Huntington Hospital in Huntington, New York, said the recommendations will encourage clinicians to be more discerning about actual risk in individual cases rather than follow the previous blanket recommendation to stop these agents before procedures requiring sedation. 

While GLP-1 RAs were prescribed for the relatively small number of patients with diabetes, he said, the risk was not apparent but became clearer with the widespread use of these agents for weight loss — often unregulated and undisclosed to care providers.

“The pendulum shifted too far the other way, and now it’s shifted back,” he said in an interview. “The new guidance is great because now we can be more thoughtful about managing individual patients.” He cited, for instance, the recommendations on the greater risk in patients in the dose escalation phase or on higher doses, and the risk-reducing measure of a liquid diet for 24 hours before surgery.

His center is already using point-of-care ultrasound and recently had a case in which a patient who forgot and took his GLP-1 RA before a scheduled procedure was found on ultrasound to have a full stomach. “In some cases, these drugs can cause an almost gastroparesis level of delayed emptying,” Purow said.

Purow thinks this early guidance will probably progress to firm guidelines within a year. Schulman is more cautious. “Our understanding of this complex topic is increasing rapidly, and ongoing clinical research will ultimately lead to evidence-based guidelines in this changing landscape,” she said.

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Schulman is a consultant for Apollo Endosurgery, Boston Scientific, Olympus, Microtech, and Fractyl. Purow had no competing interests to declare.

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

The majority of patients may safely take glucagon-like peptide 1 receptor agonists (GLP-1 RAs) before elective surgery and gastrointestinal endoscopies, according to updated guidance from five medical societies.

The new guidance, contrasting with earlier recommendations, says these incrementally used agents can be taken up until the day of surgery, but patients are advised to follow a liquid diet for 24 hours before the procedure. The decision to proceed with endoscopy and other procedures should be based on shared decision-making with the patient and interdisciplinary care teams in conjunction with minimization of the aspiration risk from delayed gastric emptying, the guidance stresses.

The five endorsing organizations are the American Society for Metabolic and Bariatric Surgery, American Society of Anesthesiologists (ASA), American Gastroenterological Association, International Society of Perioperative Care of Patients with Obesity, and Society of American Gastrointestinal and Endoscopic Surgeons. The societies emphasize that the statement is intended as guidance only and is not an evidence-based formal guideline.

GLP-1 RAs are known to delay gastric emptying, raising concerns about regurgitation, aspiration, and airway compromise during anesthesia. Rare serious adverse events have also been observed, prompting the ASA in 2023 to recommend holding these agents for 1 week for the injectable form and 1 day for the oral form before all procedures requiring anesthesia. 

 

University of Michigan

That abundance of caution, however, had negative impacts of its own. “This guidance has led to cancellations and postponements of many endoscopic and surgical procedures or required patients to undergo general anesthesia who may otherwise have had their procedures performed under moderate sedation,” said guidance coauthor Allison R. Schulman, MD, MPH, an associate professor of medicine and surgery and chief of endoscopy at the University of Michigan in Ann Arbor. “Nearly all institutions have been forced to revise preprocedural protocols, despite a lack of high-level evidence to suggest that these adjustments are necessary.”

“Studies have yielded mixed results as to whether patients on GLP-1s are at increased risk of these events, and the limited data available are inconsistent,” Schulman said. “As a result, there are inconsistencies in the recommendations from various societies leading to growing uncertainty with proceduralists on how to provide safe, effective, and timely procedural care to patients taking GLP-1 RAs.”

The new joint-society guidance may alleviate some of the uncertainty. Among the recommendations:

• Continuing GLP-1 RAs in the perioperative period should be based on shared decision-making with the patient and all care teams balancing the metabolic need for the GLP-1 RA with individual patient risk.
• Certain variables may increase the risk for delayed gastric emptying and aspiration with the periprocedural use of GLP-1 RAs: escalation phase — This phase vs the maintenance phase is associated with a higher risk for delayed gastric emptying; higher dose — the higher the dose, the greater the risk for gastrointestinal (GI) side effects; weekly dosing — GI side effects are more common with weekly vs daily formulations; presence of GI symptoms — nausea, vomiting, abdominal pain, dyspepsia, and constipation may suggest delayed gastric emptying; and medical problems beyond GLP-1 RA indications with GI effects — assess for such conditions as bowel dysmotility, gastroparesis, and Parkinson’s disease.
• Risk factors should be assessed in advance to allow sufficient time to adjust preoperative care, including diet modification and medication bridging if GLP-1 RA cessation is deemed advisable.
• If retained gastric contents are a concern on the day of a procedure, point-of-care gastric ultrasound could be used to assess aspiration risk, resources permitting.
• The aspiration risk from delayed gastric emptying should be minimized by preoperative diet modification and/or altering the anesthesia plan to consider rapid sequence induction of general anesthesia for tracheal intubation. A 24-hour preoperative liquid diet, as before colonoscopy and bariatric surgery, can be utilized when delayed gastric emptying is a concern.
• When concern about retained gastric contents exists on procedure day, providers should engage patients in a shared decision-making model and consider the benefits and risks of rapid-sequence induction of general anesthesia for tracheal intubation to minimize aspiration risk vs procedure cancellation.

“Safe continuation of surgery and gastrointestinal endoscopy, and prevention of procedure cancellation, for patients on GLP-1 RAs can be prioritized following the recommendations above, as would occur for other patient populations with gastroparesis,” the guidance panel wrote.

 

Digestive Health Center of Huntington

Commenting on the statement but not involved in it, David B. Purow, MD, managing director of the Digestive Health Center at Northwell Health/Huntington Hospital in Huntington, New York, said the recommendations will encourage clinicians to be more discerning about actual risk in individual cases rather than follow the previous blanket recommendation to stop these agents before procedures requiring sedation. 

While GLP-1 RAs were prescribed for the relatively small number of patients with diabetes, he said, the risk was not apparent but became clearer with the widespread use of these agents for weight loss — often unregulated and undisclosed to care providers.

“The pendulum shifted too far the other way, and now it’s shifted back,” he said in an interview. “The new guidance is great because now we can be more thoughtful about managing individual patients.” He cited, for instance, the recommendations on the greater risk in patients in the dose escalation phase or on higher doses, and the risk-reducing measure of a liquid diet for 24 hours before surgery.

His center is already using point-of-care ultrasound and recently had a case in which a patient who forgot and took his GLP-1 RA before a scheduled procedure was found on ultrasound to have a full stomach. “In some cases, these drugs can cause an almost gastroparesis level of delayed emptying,” Purow said.

Purow thinks this early guidance will probably progress to firm guidelines within a year. Schulman is more cautious. “Our understanding of this complex topic is increasing rapidly, and ongoing clinical research will ultimately lead to evidence-based guidelines in this changing landscape,” she said.

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Schulman is a consultant for Apollo Endosurgery, Boston Scientific, Olympus, Microtech, and Fractyl. Purow had no competing interests to declare.

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

The majority of patients may safely take glucagon-like peptide 1 receptor agonists (GLP-1 RAs) before elective surgery and gastrointestinal endoscopies, according to updated guidance from five medical societies.

The new guidance, contrasting with earlier recommendations, says these incrementally used agents can be taken up until the day of surgery, but patients are advised to follow a liquid diet for 24 hours before the procedure. The decision to proceed with endoscopy and other procedures should be based on shared decision-making with the patient and interdisciplinary care teams in conjunction with minimization of the aspiration risk from delayed gastric emptying, the guidance stresses.

The five endorsing organizations are the American Society for Metabolic and Bariatric Surgery, American Society of Anesthesiologists (ASA), American Gastroenterological Association, International Society of Perioperative Care of Patients with Obesity, and Society of American Gastrointestinal and Endoscopic Surgeons. The societies emphasize that the statement is intended as guidance only and is not an evidence-based formal guideline.

GLP-1 RAs are known to delay gastric emptying, raising concerns about regurgitation, aspiration, and airway compromise during anesthesia. Rare serious adverse events have also been observed, prompting the ASA in 2023 to recommend holding these agents for 1 week for the injectable form and 1 day for the oral form before all procedures requiring anesthesia. 

 

University of Michigan

That abundance of caution, however, had negative impacts of its own. “This guidance has led to cancellations and postponements of many endoscopic and surgical procedures or required patients to undergo general anesthesia who may otherwise have had their procedures performed under moderate sedation,” said guidance coauthor Allison R. Schulman, MD, MPH, an associate professor of medicine and surgery and chief of endoscopy at the University of Michigan in Ann Arbor. “Nearly all institutions have been forced to revise preprocedural protocols, despite a lack of high-level evidence to suggest that these adjustments are necessary.”

“Studies have yielded mixed results as to whether patients on GLP-1s are at increased risk of these events, and the limited data available are inconsistent,” Schulman said. “As a result, there are inconsistencies in the recommendations from various societies leading to growing uncertainty with proceduralists on how to provide safe, effective, and timely procedural care to patients taking GLP-1 RAs.”

The new joint-society guidance may alleviate some of the uncertainty. Among the recommendations:

• Continuing GLP-1 RAs in the perioperative period should be based on shared decision-making with the patient and all care teams balancing the metabolic need for the GLP-1 RA with individual patient risk.
• Certain variables may increase the risk for delayed gastric emptying and aspiration with the periprocedural use of GLP-1 RAs: escalation phase — This phase vs the maintenance phase is associated with a higher risk for delayed gastric emptying; higher dose — the higher the dose, the greater the risk for gastrointestinal (GI) side effects; weekly dosing — GI side effects are more common with weekly vs daily formulations; presence of GI symptoms — nausea, vomiting, abdominal pain, dyspepsia, and constipation may suggest delayed gastric emptying; and medical problems beyond GLP-1 RA indications with GI effects — assess for such conditions as bowel dysmotility, gastroparesis, and Parkinson’s disease.
• Risk factors should be assessed in advance to allow sufficient time to adjust preoperative care, including diet modification and medication bridging if GLP-1 RA cessation is deemed advisable.
• If retained gastric contents are a concern on the day of a procedure, point-of-care gastric ultrasound could be used to assess aspiration risk, resources permitting.
• The aspiration risk from delayed gastric emptying should be minimized by preoperative diet modification and/or altering the anesthesia plan to consider rapid sequence induction of general anesthesia for tracheal intubation. A 24-hour preoperative liquid diet, as before colonoscopy and bariatric surgery, can be utilized when delayed gastric emptying is a concern.
• When concern about retained gastric contents exists on procedure day, providers should engage patients in a shared decision-making model and consider the benefits and risks of rapid-sequence induction of general anesthesia for tracheal intubation to minimize aspiration risk vs procedure cancellation.

“Safe continuation of surgery and gastrointestinal endoscopy, and prevention of procedure cancellation, for patients on GLP-1 RAs can be prioritized following the recommendations above, as would occur for other patient populations with gastroparesis,” the guidance panel wrote.

 

Digestive Health Center of Huntington

Commenting on the statement but not involved in it, David B. Purow, MD, managing director of the Digestive Health Center at Northwell Health/Huntington Hospital in Huntington, New York, said the recommendations will encourage clinicians to be more discerning about actual risk in individual cases rather than follow the previous blanket recommendation to stop these agents before procedures requiring sedation. 

While GLP-1 RAs were prescribed for the relatively small number of patients with diabetes, he said, the risk was not apparent but became clearer with the widespread use of these agents for weight loss — often unregulated and undisclosed to care providers.

“The pendulum shifted too far the other way, and now it’s shifted back,” he said in an interview. “The new guidance is great because now we can be more thoughtful about managing individual patients.” He cited, for instance, the recommendations on the greater risk in patients in the dose escalation phase or on higher doses, and the risk-reducing measure of a liquid diet for 24 hours before surgery.

His center is already using point-of-care ultrasound and recently had a case in which a patient who forgot and took his GLP-1 RA before a scheduled procedure was found on ultrasound to have a full stomach. “In some cases, these drugs can cause an almost gastroparesis level of delayed emptying,” Purow said.

Purow thinks this early guidance will probably progress to firm guidelines within a year. Schulman is more cautious. “Our understanding of this complex topic is increasing rapidly, and ongoing clinical research will ultimately lead to evidence-based guidelines in this changing landscape,” she said.

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Schulman is a consultant for Apollo Endosurgery, Boston Scientific, Olympus, Microtech, and Fractyl. Purow had no competing interests to declare.

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

PHILADELPHIA — A new 10-day treatment regimen with the oral potassium-competitive acid blocker vonoprazan, and the antibiotics levofloxacin and amoxicillin, was significantly more effective at eradicating Helicobacter pylori infection than triple therapy with omeprazole, amoxicillin, and clarithromycin, according to the results of a randomized, multicenter study.

In addition, the triple therapy regimen with vonoprazan was generally better tolerated than the 14-day omeprazole-based regimen.

The new treatment combination was created to tackle the two main reasons that patients with H pylori experience treatment failure: Inadequate acid suppressant activity and antibiotic resistance, said principal investigator Kachonsak Yongwatana, MD, from Phramongkutklao Hospital in Bangkok, Thailand.

“Vonoprazan” is the more potent option for acid suppression, and “levofloxacin” addresses antibiotic resistance, he explained.

Yongwatana presented the findings (Abstract 41) at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting. The ACG recently released a clinical guideline on the treatment of H pylori infection. 
 

Robust Eradication Rates

Yongwatana and colleagues enrolled adult patients with H pylori infections at four hospitals in Thailand between December 2022 and September 2023. The presence of H pylori was confirmed by upper gastrointestinal endoscopy with positive rapid urease test or positive test on tissue biopsy. 

Patients were then randomized into two treatment groups: The 10-day VAL group (vonoprazan 20 mg twice daily, amoxicillin 1000 mg twice daily, and levofloxacin 500 mg once daily for 10 days) and the 14-day OAC group (omeprazole 20 mg twice daily, amoxicillin 1000 mg twice daily, and clarithromycin 500 mg twice daily for 14 days). Eradication was assessed by urea breath test 4 weeks after completion of treatment.

There were 280 patients in total, with 140 in each group. There were no significant differences in baseline characteristics between the groups. The most common endoscopic findings among all participants included erosive gastritis (38%), nonerosive gastritis (27%), and gastric ulcer (17%). 

In comparing the treatments, the researchers found that 10-day VAL led to significantly greater H pylori eradication rate than the 14-day OAC group in both intention-to-treat analysis (91.4 % vs 80.7%, P = .009) and per-protocol analysis (93.4% vs 83.7%, P = .012). 

Vonoprazan-based therapy was also well tolerated by participants. Patients in the 10-day VAL group had significantly lower rates of experiencing a bitter taste (2.1% vs 42.9%, P < .001) and bloating (5% vs 12.1%, P = .033) than those in the 14-day OAC group. 
 

Isolating the BMI Effect

The researchers conducted a subgroup analysis on potential factors influencing response, which revealed that having a body mass index (BMI) < 23.5 was significantly associated with a higher chance at successful H pylori eradication (relative risk [RR], 2.27; P = .049). 

They then analyzed whether this BMI threshold was predictive in the separate treatment regimens. Although having a BMI < 23.5 was significantly associated with a higher eradication rate in the 14-day OAC group (RR, 3.34; P = .026), no such effect was noted in the 10-day VAL group (RR, 1.10; P = .888).

The influence of BMI could be caused by the bioavailability of the treatments used in the regimen, Younwatana said in an interview. He and his colleagues recommended against using the 14-day OAC regimen in those with BMI ≥ 23.5.

“In patients with a high BMI, we should be concerned that normal proton pump inhibitors may not work,” he said. “You have to step up to the higher-potency options.” 
 

Seeking Confirmation in Other Populations

Session comoderator Felice Schnoll-Sussman, MD, MSc, professor of clinical medicine and the director of the Jay Monahan Center for Gastrointestinal Health, director of the DIGEST program, and the associate chair of medicine for Outreach and Network at New York–Presbyterian Brooklyn Methodist Hospital in New York City, said in an interview that the promising results merit confirmation in other populations. 

“When you see a study that is coming out of one country, when there could be issues related to antibiotic sensitivity in H pylori, it really is important to decide whether or not this is applicable to other patient populations,” said Schnoll-Sussman, who was not involved in the study. 

She noted that this is also true of the findings from the subgroup as it is unclear whether average rates of BMI are notably lower in Thailand from other countries.

“As we know, BMI affects so many things with disease states. So, it’s a possibility in a country where the BMI is actually lower, there may be something else about these individuals in terms of their wellness status that could be underlying the effect.” 

The study had no specific funding, although Takeda supplied treatments used in the analysis. Yongwatana reported no relevant financial relationships. Schnoll-Sussman reported serving as an advisory committee/board member for Braintree, Ethicon, Implantica, and Phathom. 

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

PHILADELPHIA — A new 10-day treatment regimen with the oral potassium-competitive acid blocker vonoprazan, and the antibiotics levofloxacin and amoxicillin, was significantly more effective at eradicating Helicobacter pylori infection than triple therapy with omeprazole, amoxicillin, and clarithromycin, according to the results of a randomized, multicenter study.

In addition, the triple therapy regimen with vonoprazan was generally better tolerated than the 14-day omeprazole-based regimen.

The new treatment combination was created to tackle the two main reasons that patients with H pylori experience treatment failure: Inadequate acid suppressant activity and antibiotic resistance, said principal investigator Kachonsak Yongwatana, MD, from Phramongkutklao Hospital in Bangkok, Thailand.

“Vonoprazan” is the more potent option for acid suppression, and “levofloxacin” addresses antibiotic resistance, he explained.

Yongwatana presented the findings (Abstract 41) at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting. The ACG recently released a clinical guideline on the treatment of H pylori infection. 
 

Robust Eradication Rates

Yongwatana and colleagues enrolled adult patients with H pylori infections at four hospitals in Thailand between December 2022 and September 2023. The presence of H pylori was confirmed by upper gastrointestinal endoscopy with positive rapid urease test or positive test on tissue biopsy. 

Patients were then randomized into two treatment groups: The 10-day VAL group (vonoprazan 20 mg twice daily, amoxicillin 1000 mg twice daily, and levofloxacin 500 mg once daily for 10 days) and the 14-day OAC group (omeprazole 20 mg twice daily, amoxicillin 1000 mg twice daily, and clarithromycin 500 mg twice daily for 14 days). Eradication was assessed by urea breath test 4 weeks after completion of treatment.

There were 280 patients in total, with 140 in each group. There were no significant differences in baseline characteristics between the groups. The most common endoscopic findings among all participants included erosive gastritis (38%), nonerosive gastritis (27%), and gastric ulcer (17%). 

In comparing the treatments, the researchers found that 10-day VAL led to significantly greater H pylori eradication rate than the 14-day OAC group in both intention-to-treat analysis (91.4 % vs 80.7%, P = .009) and per-protocol analysis (93.4% vs 83.7%, P = .012). 

Vonoprazan-based therapy was also well tolerated by participants. Patients in the 10-day VAL group had significantly lower rates of experiencing a bitter taste (2.1% vs 42.9%, P < .001) and bloating (5% vs 12.1%, P = .033) than those in the 14-day OAC group. 
 

Isolating the BMI Effect

The researchers conducted a subgroup analysis on potential factors influencing response, which revealed that having a body mass index (BMI) < 23.5 was significantly associated with a higher chance at successful H pylori eradication (relative risk [RR], 2.27; P = .049). 

They then analyzed whether this BMI threshold was predictive in the separate treatment regimens. Although having a BMI < 23.5 was significantly associated with a higher eradication rate in the 14-day OAC group (RR, 3.34; P = .026), no such effect was noted in the 10-day VAL group (RR, 1.10; P = .888).

The influence of BMI could be caused by the bioavailability of the treatments used in the regimen, Younwatana said in an interview. He and his colleagues recommended against using the 14-day OAC regimen in those with BMI ≥ 23.5.

“In patients with a high BMI, we should be concerned that normal proton pump inhibitors may not work,” he said. “You have to step up to the higher-potency options.” 
 

Seeking Confirmation in Other Populations

Session comoderator Felice Schnoll-Sussman, MD, MSc, professor of clinical medicine and the director of the Jay Monahan Center for Gastrointestinal Health, director of the DIGEST program, and the associate chair of medicine for Outreach and Network at New York–Presbyterian Brooklyn Methodist Hospital in New York City, said in an interview that the promising results merit confirmation in other populations. 

“When you see a study that is coming out of one country, when there could be issues related to antibiotic sensitivity in H pylori, it really is important to decide whether or not this is applicable to other patient populations,” said Schnoll-Sussman, who was not involved in the study. 

She noted that this is also true of the findings from the subgroup as it is unclear whether average rates of BMI are notably lower in Thailand from other countries.

“As we know, BMI affects so many things with disease states. So, it’s a possibility in a country where the BMI is actually lower, there may be something else about these individuals in terms of their wellness status that could be underlying the effect.” 

The study had no specific funding, although Takeda supplied treatments used in the analysis. Yongwatana reported no relevant financial relationships. Schnoll-Sussman reported serving as an advisory committee/board member for Braintree, Ethicon, Implantica, and Phathom. 

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

PHILADELPHIA — A new 10-day treatment regimen with the oral potassium-competitive acid blocker vonoprazan, and the antibiotics levofloxacin and amoxicillin, was significantly more effective at eradicating Helicobacter pylori infection than triple therapy with omeprazole, amoxicillin, and clarithromycin, according to the results of a randomized, multicenter study.

In addition, the triple therapy regimen with vonoprazan was generally better tolerated than the 14-day omeprazole-based regimen.

The new treatment combination was created to tackle the two main reasons that patients with H pylori experience treatment failure: Inadequate acid suppressant activity and antibiotic resistance, said principal investigator Kachonsak Yongwatana, MD, from Phramongkutklao Hospital in Bangkok, Thailand.

“Vonoprazan” is the more potent option for acid suppression, and “levofloxacin” addresses antibiotic resistance, he explained.

Yongwatana presented the findings (Abstract 41) at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting. The ACG recently released a clinical guideline on the treatment of H pylori infection. 
 

Robust Eradication Rates

Yongwatana and colleagues enrolled adult patients with H pylori infections at four hospitals in Thailand between December 2022 and September 2023. The presence of H pylori was confirmed by upper gastrointestinal endoscopy with positive rapid urease test or positive test on tissue biopsy. 

Patients were then randomized into two treatment groups: The 10-day VAL group (vonoprazan 20 mg twice daily, amoxicillin 1000 mg twice daily, and levofloxacin 500 mg once daily for 10 days) and the 14-day OAC group (omeprazole 20 mg twice daily, amoxicillin 1000 mg twice daily, and clarithromycin 500 mg twice daily for 14 days). Eradication was assessed by urea breath test 4 weeks after completion of treatment.

There were 280 patients in total, with 140 in each group. There were no significant differences in baseline characteristics between the groups. The most common endoscopic findings among all participants included erosive gastritis (38%), nonerosive gastritis (27%), and gastric ulcer (17%). 

In comparing the treatments, the researchers found that 10-day VAL led to significantly greater H pylori eradication rate than the 14-day OAC group in both intention-to-treat analysis (91.4 % vs 80.7%, P = .009) and per-protocol analysis (93.4% vs 83.7%, P = .012). 

Vonoprazan-based therapy was also well tolerated by participants. Patients in the 10-day VAL group had significantly lower rates of experiencing a bitter taste (2.1% vs 42.9%, P < .001) and bloating (5% vs 12.1%, P = .033) than those in the 14-day OAC group. 
 

Isolating the BMI Effect

The researchers conducted a subgroup analysis on potential factors influencing response, which revealed that having a body mass index (BMI) < 23.5 was significantly associated with a higher chance at successful H pylori eradication (relative risk [RR], 2.27; P = .049). 

They then analyzed whether this BMI threshold was predictive in the separate treatment regimens. Although having a BMI < 23.5 was significantly associated with a higher eradication rate in the 14-day OAC group (RR, 3.34; P = .026), no such effect was noted in the 10-day VAL group (RR, 1.10; P = .888).

The influence of BMI could be caused by the bioavailability of the treatments used in the regimen, Younwatana said in an interview. He and his colleagues recommended against using the 14-day OAC regimen in those with BMI ≥ 23.5.

“In patients with a high BMI, we should be concerned that normal proton pump inhibitors may not work,” he said. “You have to step up to the higher-potency options.” 
 

Seeking Confirmation in Other Populations

Session comoderator Felice Schnoll-Sussman, MD, MSc, professor of clinical medicine and the director of the Jay Monahan Center for Gastrointestinal Health, director of the DIGEST program, and the associate chair of medicine for Outreach and Network at New York–Presbyterian Brooklyn Methodist Hospital in New York City, said in an interview that the promising results merit confirmation in other populations. 

“When you see a study that is coming out of one country, when there could be issues related to antibiotic sensitivity in H pylori, it really is important to decide whether or not this is applicable to other patient populations,” said Schnoll-Sussman, who was not involved in the study. 

She noted that this is also true of the findings from the subgroup as it is unclear whether average rates of BMI are notably lower in Thailand from other countries.

“As we know, BMI affects so many things with disease states. So, it’s a possibility in a country where the BMI is actually lower, there may be something else about these individuals in terms of their wellness status that could be underlying the effect.” 

The study had no specific funding, although Takeda supplied treatments used in the analysis. Yongwatana reported no relevant financial relationships. Schnoll-Sussman reported serving as an advisory committee/board member for Braintree, Ethicon, Implantica, and Phathom. 

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

PHILADELPHIA — Artificial intelligence–assisted colonoscopy (AIAC) with computer-aided detection (CADe) technology may improve adenoma detection rate (ADR), but it’s also associated with higher detection and removal of non-neoplastic lesions, according to a study presented at the annual meeting of the American College of Gastroenterology (ACG).

In particular, AIAC led to a statistically and clinically significant increase in the proportion of exams that detected lesions that after resection were all found to be benign, compared with unassisted colonoscopy.

University of Minnesota

“The potential implications include increased procedural risks, as well as costs, such as pathology costs and other healthcare expenditures, without any additional colorectal cancer prevention benefit,” said lead author Tessa Herman, MD, chief resident of internal medicine at the University of Minnesota, Minneapolis, and Minneapolis Veterans Affairs Health Care System.

In a previous implementation trial at the Minneapolis VA Medical Center, Herman and colleagues compared ADR between a group of patients undergoing AIAC and a historical cohort of patients who had non–AI-assisted colonoscopy.

In this subsequent study, the research team conducted an ad hoc analysis of data from the previous trial to determine the proportion of colonoscopies for screening, surveillance, and positive fecal immunochemical tests which detect lesions that after resection are all found to be benign. They excluded colonoscopies conducted for diagnostic indications or inflammatory bowel disease, as well as incomplete colonoscopies, and for those with inadequate bowel preparation.

Overall, they studied 441 non-AIAC colonoscopies (between November 2022 and April 2023) and 599 AIAC colonoscopies (between May 2023 and October 2023). The groups were balanced, and there were no significant differences in patient demographics, endoscopists, AI technology, procedure time, or average number of polyps detected.

In the non-AIAC cohort, 37 cases (8.4%) had polypectomies that revealed only benign lesions, as compared with 74 cases (12.4%) in the AIAC cohort. The most common resected lesions were benign colonic mucosa, lymphoid aggregates, and hyperplastic polyps.

Applied to the 15 million colonoscopies conducted in the United States per year, the findings indicate that full adoption of AIAC could result in about 600,000 more colonoscopies in which only benign, nonadenomatous lesions are removed, compared with traditional colonoscopy, Herman said.

More study of AIAC is needed, said Daniel Pambianco, MD, managing partner of GastroHealth-Charlottesville in Virginia and the 2023 ACG president. “This technology is in a fledging stage, and the more data we have, the more helpful it’ll be to know if we’re removing the right lesions at a better rate.”

“There’s a hope that assistance will improve detection, removal of polyps, and ultimately, colon cancer,” added Pambianco, who comoderated the session on colorectal cancer prevention.

Future longitudinal studies should monitor both ADR and benign lesion resection rates with AIAC, and modeling studies could determine the benefits and costs of the technology, Herman said. In addition, development of hybrid CADe and computer-aided diagnosis systems could mitigate concerns about excessive benign lesion resection with AI tools.

Valley Medical Group

Clinicians already are able to find colon mucosa that are polypoid or lymphoid aggregates during colonoscopy without AI assistance, said the session’s comoderator, Sita Chokhavatia, MD, AGAF, a gastroenterologist with Valley Medical Group in Ridgewood, New Jersey. 

“Instead, we need a tool that can help us to not remove these polyps that are not neoplastic,” she said. “With future developments, we may be able to take it to the next step where the algorithm tells us that it’s benign and not to touch it.”

The study was named an ACG Newsworthy Abstract. Herman, Pambianco, and Chokhavatia reported no relevant disclosures.

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

PHILADELPHIA — Artificial intelligence–assisted colonoscopy (AIAC) with computer-aided detection (CADe) technology may improve adenoma detection rate (ADR), but it’s also associated with higher detection and removal of non-neoplastic lesions, according to a study presented at the annual meeting of the American College of Gastroenterology (ACG).

In particular, AIAC led to a statistically and clinically significant increase in the proportion of exams that detected lesions that after resection were all found to be benign, compared with unassisted colonoscopy.

University of Minnesota

“The potential implications include increased procedural risks, as well as costs, such as pathology costs and other healthcare expenditures, without any additional colorectal cancer prevention benefit,” said lead author Tessa Herman, MD, chief resident of internal medicine at the University of Minnesota, Minneapolis, and Minneapolis Veterans Affairs Health Care System.

In a previous implementation trial at the Minneapolis VA Medical Center, Herman and colleagues compared ADR between a group of patients undergoing AIAC and a historical cohort of patients who had non–AI-assisted colonoscopy.

In this subsequent study, the research team conducted an ad hoc analysis of data from the previous trial to determine the proportion of colonoscopies for screening, surveillance, and positive fecal immunochemical tests which detect lesions that after resection are all found to be benign. They excluded colonoscopies conducted for diagnostic indications or inflammatory bowel disease, as well as incomplete colonoscopies, and for those with inadequate bowel preparation.

Overall, they studied 441 non-AIAC colonoscopies (between November 2022 and April 2023) and 599 AIAC colonoscopies (between May 2023 and October 2023). The groups were balanced, and there were no significant differences in patient demographics, endoscopists, AI technology, procedure time, or average number of polyps detected.

In the non-AIAC cohort, 37 cases (8.4%) had polypectomies that revealed only benign lesions, as compared with 74 cases (12.4%) in the AIAC cohort. The most common resected lesions were benign colonic mucosa, lymphoid aggregates, and hyperplastic polyps.

Applied to the 15 million colonoscopies conducted in the United States per year, the findings indicate that full adoption of AIAC could result in about 600,000 more colonoscopies in which only benign, nonadenomatous lesions are removed, compared with traditional colonoscopy, Herman said.

More study of AIAC is needed, said Daniel Pambianco, MD, managing partner of GastroHealth-Charlottesville in Virginia and the 2023 ACG president. “This technology is in a fledging stage, and the more data we have, the more helpful it’ll be to know if we’re removing the right lesions at a better rate.”

“There’s a hope that assistance will improve detection, removal of polyps, and ultimately, colon cancer,” added Pambianco, who comoderated the session on colorectal cancer prevention.

Future longitudinal studies should monitor both ADR and benign lesion resection rates with AIAC, and modeling studies could determine the benefits and costs of the technology, Herman said. In addition, development of hybrid CADe and computer-aided diagnosis systems could mitigate concerns about excessive benign lesion resection with AI tools.

Valley Medical Group

Clinicians already are able to find colon mucosa that are polypoid or lymphoid aggregates during colonoscopy without AI assistance, said the session’s comoderator, Sita Chokhavatia, MD, AGAF, a gastroenterologist with Valley Medical Group in Ridgewood, New Jersey. 

“Instead, we need a tool that can help us to not remove these polyps that are not neoplastic,” she said. “With future developments, we may be able to take it to the next step where the algorithm tells us that it’s benign and not to touch it.”

The study was named an ACG Newsworthy Abstract. Herman, Pambianco, and Chokhavatia reported no relevant disclosures.

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

PHILADELPHIA — Artificial intelligence–assisted colonoscopy (AIAC) with computer-aided detection (CADe) technology may improve adenoma detection rate (ADR), but it’s also associated with higher detection and removal of non-neoplastic lesions, according to a study presented at the annual meeting of the American College of Gastroenterology (ACG).

In particular, AIAC led to a statistically and clinically significant increase in the proportion of exams that detected lesions that after resection were all found to be benign, compared with unassisted colonoscopy.

University of Minnesota

“The potential implications include increased procedural risks, as well as costs, such as pathology costs and other healthcare expenditures, without any additional colorectal cancer prevention benefit,” said lead author Tessa Herman, MD, chief resident of internal medicine at the University of Minnesota, Minneapolis, and Minneapolis Veterans Affairs Health Care System.

In a previous implementation trial at the Minneapolis VA Medical Center, Herman and colleagues compared ADR between a group of patients undergoing AIAC and a historical cohort of patients who had non–AI-assisted colonoscopy.

In this subsequent study, the research team conducted an ad hoc analysis of data from the previous trial to determine the proportion of colonoscopies for screening, surveillance, and positive fecal immunochemical tests which detect lesions that after resection are all found to be benign. They excluded colonoscopies conducted for diagnostic indications or inflammatory bowel disease, as well as incomplete colonoscopies, and for those with inadequate bowel preparation.

Overall, they studied 441 non-AIAC colonoscopies (between November 2022 and April 2023) and 599 AIAC colonoscopies (between May 2023 and October 2023). The groups were balanced, and there were no significant differences in patient demographics, endoscopists, AI technology, procedure time, or average number of polyps detected.

In the non-AIAC cohort, 37 cases (8.4%) had polypectomies that revealed only benign lesions, as compared with 74 cases (12.4%) in the AIAC cohort. The most common resected lesions were benign colonic mucosa, lymphoid aggregates, and hyperplastic polyps.

Applied to the 15 million colonoscopies conducted in the United States per year, the findings indicate that full adoption of AIAC could result in about 600,000 more colonoscopies in which only benign, nonadenomatous lesions are removed, compared with traditional colonoscopy, Herman said.

More study of AIAC is needed, said Daniel Pambianco, MD, managing partner of GastroHealth-Charlottesville in Virginia and the 2023 ACG president. “This technology is in a fledging stage, and the more data we have, the more helpful it’ll be to know if we’re removing the right lesions at a better rate.”

“There’s a hope that assistance will improve detection, removal of polyps, and ultimately, colon cancer,” added Pambianco, who comoderated the session on colorectal cancer prevention.

Future longitudinal studies should monitor both ADR and benign lesion resection rates with AIAC, and modeling studies could determine the benefits and costs of the technology, Herman said. In addition, development of hybrid CADe and computer-aided diagnosis systems could mitigate concerns about excessive benign lesion resection with AI tools.

Valley Medical Group

Clinicians already are able to find colon mucosa that are polypoid or lymphoid aggregates during colonoscopy without AI assistance, said the session’s comoderator, Sita Chokhavatia, MD, AGAF, a gastroenterologist with Valley Medical Group in Ridgewood, New Jersey. 

“Instead, we need a tool that can help us to not remove these polyps that are not neoplastic,” she said. “With future developments, we may be able to take it to the next step where the algorithm tells us that it’s benign and not to touch it.”

The study was named an ACG Newsworthy Abstract. Herman, Pambianco, and Chokhavatia reported no relevant disclosures.

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

PHILADELPHIA — New research challenges the traditional practice of continuing vasoconstrictor therapy for 5 days after endoscopic variceal ligation (EVL) for acute variceal bleeding, finding that a shorter course of 1-3 days may suffice, without raising the risk for rebleeding, if the initial ligation successfully controls bleeding.

“This approach would allow earlier discharge from the hospital and reduce the risk of adverse events, all without sacrificing treatment efficacy or compromising patient safety,” Sushrut Ingawale, MD, MBBS, Quinnipiac University School of Medicine, North Haven, and St. Vincent’s Medical Center, Bridgeport, both in Connecticut, said in a presentation at the annual meeting of the American College of Gastroenterology (ACG).

Ingawale called for a “re-evaluation of existing protocols, emphasizing the potential to update current protocols to reflect shorter, more personalized” duration of vasoconstrictor therapy in these patients.

Rush University Medical Center

Commenting on this research, Nancy Reau, MD, AGAF, of Rush University in Chicago, Illinois, said: “We should always question the standard of care.”

“Vasoconstrictors for 5 days is the standard of care, but this could lead to prolonged hospitalization in patients who are otherwise doing well after endoscopic intervention. Recognizing that a shorter course of vasoconstrictor treatment may have equal outcome is very important though it may not be appropriate for all patients, especially those at high risk for rebleeding,” said Reau.
 

Outdated Guidelines?

In his presentation, Ingawale noted that current guidelines that recommend continuing vasoconstrictors, like octreotide or terlipressin, for at least 3-5 days after EVL for acute variceal bleeding are based primarily on old studies in which sclerotherapy was the primary hemostatic method.

The study team assessed comparative outcomes based on the duration of vasoconstrictors after EVL for acute variceal bleeding in a systematic review and network meta-analysis of 11 randomized controlled trials.

The studies had a total of 816 patients who were grouped based on the duration vasoconstrictor therapy: 24 hours or less (group 1), 24-72 hours (group 2), and 72-120 hours (group 3).

There was no significant difference in the risk for rebleeding in group 1 (risk ratio [RR], 1.36; 95% CI, 0.48-3.52) and group 2 (RR, 1.34; 95% CI, 0.42-4.54) vs group 3.

“This finding was even consistent when we compared individual durations” of 0, 12, 24, 48, and 72 hours vs 120 hours, Ingawale said.

There was also no statistically significant difference in the 5-day mortality risk between group 1 (RR, 0.66; 95% CI, 0.09-2.52) and group 2 (RR, 1.08; 95% CI, 0.15-6.43) or the 30-day mortality risk between group 1 (RR, 1.18; 95% CI, 0.51-2.51) and group 2 (RR, 0.98; 95% CI, 0.36-2.52) vs group 3.
 

Rapidly Evolving Area

“Our network meta-analysis did not show any benefit of continuing vasoconstrictors after EVL,” the researchers wrote in their conference abstract. Despite historical precedent, shorter durations may be adequate, “potentially enabling earlier hospital discharge without compromising patient outcomes.”

Ingawale suggested future research should look to identify the subset of patients at a risk for failure to control bleeding who might benefit from the continuation of vasoconstrictors.

“Management of complications of portal hypertension are rapidly evolving and this study will add to the data that drives our guidelines. Seeing this data in a peer reviewed publication will add the necessary validity to impact a change in the treatment paradigm,” Reau said.

The study had no specific funding. Ingawale had no relevant financial relationships. Reau disclosed various relationships with AbbVie, Gilead, Arbutus, Intercept, and Salix.

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

PHILADELPHIA — New research challenges the traditional practice of continuing vasoconstrictor therapy for 5 days after endoscopic variceal ligation (EVL) for acute variceal bleeding, finding that a shorter course of 1-3 days may suffice, without raising the risk for rebleeding, if the initial ligation successfully controls bleeding.

“This approach would allow earlier discharge from the hospital and reduce the risk of adverse events, all without sacrificing treatment efficacy or compromising patient safety,” Sushrut Ingawale, MD, MBBS, Quinnipiac University School of Medicine, North Haven, and St. Vincent’s Medical Center, Bridgeport, both in Connecticut, said in a presentation at the annual meeting of the American College of Gastroenterology (ACG).

Ingawale called for a “re-evaluation of existing protocols, emphasizing the potential to update current protocols to reflect shorter, more personalized” duration of vasoconstrictor therapy in these patients.

Rush University Medical Center

Commenting on this research, Nancy Reau, MD, AGAF, of Rush University in Chicago, Illinois, said: “We should always question the standard of care.”

“Vasoconstrictors for 5 days is the standard of care, but this could lead to prolonged hospitalization in patients who are otherwise doing well after endoscopic intervention. Recognizing that a shorter course of vasoconstrictor treatment may have equal outcome is very important though it may not be appropriate for all patients, especially those at high risk for rebleeding,” said Reau.
 

Outdated Guidelines?

In his presentation, Ingawale noted that current guidelines that recommend continuing vasoconstrictors, like octreotide or terlipressin, for at least 3-5 days after EVL for acute variceal bleeding are based primarily on old studies in which sclerotherapy was the primary hemostatic method.

The study team assessed comparative outcomes based on the duration of vasoconstrictors after EVL for acute variceal bleeding in a systematic review and network meta-analysis of 11 randomized controlled trials.

The studies had a total of 816 patients who were grouped based on the duration vasoconstrictor therapy: 24 hours or less (group 1), 24-72 hours (group 2), and 72-120 hours (group 3).

There was no significant difference in the risk for rebleeding in group 1 (risk ratio [RR], 1.36; 95% CI, 0.48-3.52) and group 2 (RR, 1.34; 95% CI, 0.42-4.54) vs group 3.

“This finding was even consistent when we compared individual durations” of 0, 12, 24, 48, and 72 hours vs 120 hours, Ingawale said.

There was also no statistically significant difference in the 5-day mortality risk between group 1 (RR, 0.66; 95% CI, 0.09-2.52) and group 2 (RR, 1.08; 95% CI, 0.15-6.43) or the 30-day mortality risk between group 1 (RR, 1.18; 95% CI, 0.51-2.51) and group 2 (RR, 0.98; 95% CI, 0.36-2.52) vs group 3.
 

Rapidly Evolving Area

“Our network meta-analysis did not show any benefit of continuing vasoconstrictors after EVL,” the researchers wrote in their conference abstract. Despite historical precedent, shorter durations may be adequate, “potentially enabling earlier hospital discharge without compromising patient outcomes.”

Ingawale suggested future research should look to identify the subset of patients at a risk for failure to control bleeding who might benefit from the continuation of vasoconstrictors.

“Management of complications of portal hypertension are rapidly evolving and this study will add to the data that drives our guidelines. Seeing this data in a peer reviewed publication will add the necessary validity to impact a change in the treatment paradigm,” Reau said.

The study had no specific funding. Ingawale had no relevant financial relationships. Reau disclosed various relationships with AbbVie, Gilead, Arbutus, Intercept, and Salix.

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

PHILADELPHIA — New research challenges the traditional practice of continuing vasoconstrictor therapy for 5 days after endoscopic variceal ligation (EVL) for acute variceal bleeding, finding that a shorter course of 1-3 days may suffice, without raising the risk for rebleeding, if the initial ligation successfully controls bleeding.

“This approach would allow earlier discharge from the hospital and reduce the risk of adverse events, all without sacrificing treatment efficacy or compromising patient safety,” Sushrut Ingawale, MD, MBBS, Quinnipiac University School of Medicine, North Haven, and St. Vincent’s Medical Center, Bridgeport, both in Connecticut, said in a presentation at the annual meeting of the American College of Gastroenterology (ACG).

Ingawale called for a “re-evaluation of existing protocols, emphasizing the potential to update current protocols to reflect shorter, more personalized” duration of vasoconstrictor therapy in these patients.

Rush University Medical Center

Commenting on this research, Nancy Reau, MD, AGAF, of Rush University in Chicago, Illinois, said: “We should always question the standard of care.”

“Vasoconstrictors for 5 days is the standard of care, but this could lead to prolonged hospitalization in patients who are otherwise doing well after endoscopic intervention. Recognizing that a shorter course of vasoconstrictor treatment may have equal outcome is very important though it may not be appropriate for all patients, especially those at high risk for rebleeding,” said Reau.
 

Outdated Guidelines?

In his presentation, Ingawale noted that current guidelines that recommend continuing vasoconstrictors, like octreotide or terlipressin, for at least 3-5 days after EVL for acute variceal bleeding are based primarily on old studies in which sclerotherapy was the primary hemostatic method.

The study team assessed comparative outcomes based on the duration of vasoconstrictors after EVL for acute variceal bleeding in a systematic review and network meta-analysis of 11 randomized controlled trials.

The studies had a total of 816 patients who were grouped based on the duration vasoconstrictor therapy: 24 hours or less (group 1), 24-72 hours (group 2), and 72-120 hours (group 3).

There was no significant difference in the risk for rebleeding in group 1 (risk ratio [RR], 1.36; 95% CI, 0.48-3.52) and group 2 (RR, 1.34; 95% CI, 0.42-4.54) vs group 3.

“This finding was even consistent when we compared individual durations” of 0, 12, 24, 48, and 72 hours vs 120 hours, Ingawale said.

There was also no statistically significant difference in the 5-day mortality risk between group 1 (RR, 0.66; 95% CI, 0.09-2.52) and group 2 (RR, 1.08; 95% CI, 0.15-6.43) or the 30-day mortality risk between group 1 (RR, 1.18; 95% CI, 0.51-2.51) and group 2 (RR, 0.98; 95% CI, 0.36-2.52) vs group 3.
 

Rapidly Evolving Area

“Our network meta-analysis did not show any benefit of continuing vasoconstrictors after EVL,” the researchers wrote in their conference abstract. Despite historical precedent, shorter durations may be adequate, “potentially enabling earlier hospital discharge without compromising patient outcomes.”

Ingawale suggested future research should look to identify the subset of patients at a risk for failure to control bleeding who might benefit from the continuation of vasoconstrictors.

“Management of complications of portal hypertension are rapidly evolving and this study will add to the data that drives our guidelines. Seeing this data in a peer reviewed publication will add the necessary validity to impact a change in the treatment paradigm,” Reau said.

The study had no specific funding. Ingawale had no relevant financial relationships. Reau disclosed various relationships with AbbVie, Gilead, Arbutus, Intercept, and Salix.

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

VIENNA — Guselkumab has been shown to be efficacious vs placebo in patients with moderately to severely active Crohn’s disease (CD), regardless of prior biologic therapy exposure, according to a pooled analysis of the two phase 3 double-blind GALAXI 2 and 3 studies.

“We found that guselkumab was effective in both biologic-naive and biologic-inadequate subpopulations,” said coinvestigator Bruce E. Sands, MD, AGAF, gastroenterologist from Icahn School of Medicine at Mount Sinai, New York City.

These latest results add to the primary results of these studies reported earlier in 2024 that guselkumab was shown to be superior to both placebo and ustekinumab in the same patient population with moderately to severely active CD.

Sands reported the new data in a presentation at the United European Gastroenterology (UEG) Week 2024.

Guselkumab potently blocks interleukin (IL)–23 and binds to CD64, a receptor on cells that produce IL-23. The dual-acting IL-23p19 subunit inhibitor agent is currently under review by the Food and Drug Administration (FDA) for moderately to severely active CD. In September, guselkumab (Tremfya, Johnson & Johnson) was approved for use in moderately to severely active ulcerative colitis.
 

GALAXI 2 and 3 Pooled Dataset

In the two independent, identically designed GALAXI 2 and 3 studies, patients were randomized to guselkumab treatment at either 200 mg intravenous (IV) induction at weeks 0, 4, and 8, followed by 200 mg subcutaneous maintenance every 4 weeks, starting at week 12, or 200 mg IV induction at weeks 0, 4, and 8, followed by 100 mg subcutaneous maintenance every 8 weeks, starting at week 16; or to ustekinumab; or to placebo.

Participants were required to remain on their treatment of initial randomization for a long-term extension study (up to 5 years) looking at clinical, endoscopic, and safety outcomes, except for participants on placebo who were allowed to switch to ustekinumab if clinical response was not met at week 12.

Inclusion criteria for the studies comprised a Crohn’s Disease Activity Index score between 220 and 450, a mean daily stool frequency count > 3 or an abdominal pain score > 1, and a simple endoscopic score for CD score ≥ 6. Participants were also required to have shown an inadequate response or intolerance to oral corticosteroids, 6-mercaptopurine/azathioprine/methotrexate, or biologic therapies.

The pooled dataset included patients on either dose of guselkumab and patients on placebo (total n = 730). Of these, 52% of participants had shown a prior inadequate response to a biologic, 42% were biologic naive, and 6% had prior exposure to biologics but no documented failure. Patients on ustekinumab were not included in this analysis.

Almost all patients (97%) in the biologic-inadequate response group had previously received at least one anti–tumor necrosis factor agent, and around 15% had received vedolizumab. As expected, the biologic-inadequate responders were a lot sicker than the biologic-naive patients, Sands reported.

The composite co–primary endpoints for each guselkumab regimen vs placebo were clinical response at week 12 plus clinical remission at week 48, and clinical response at week 12 plus endoscopic response at week 48.

The major secondary endpoints comprised clinical remission at week 12 and endoscopic response also at week 12.
 

Short- and Long-Term Endpoints in Both Subgroups

In the biologic-naive subgroup, 54.7% of patients receiving the 200-mg dose regimen of guselkumab and 51.7% of those receiving the 100-mg dose regimen showed a clinical response at week 12 plus clinical remission at week 48, compared with 11.5% in the placebo group (P < .001 for both compared with placebo).

In the biologic-inadequate response group, 49.7% of those receiving the 200-mg dose regimen of guselkumab and 45.8% on the 100-mg dose regimen reached the composite endpoint, compared with the placebo response of 12.8% (P < .001 for both compared with placebo).

“You can see a slight decrease in response in the biologic-inadequate responders, but on the whole, the confidence intervals are highly overlapping,” said Sands.

Turning to major secondary endpoints at week 12, clinical remission was reached by 49.6% of the biologic-naive group on the 200-mg guselkumab regimen vs 16.4% on placebo, and by 46.0% of the biologic-inadequate group on the 200-mg regimen vs 19.2% on placebo (P < .001 for both subgroups). Endoscopic response was achieved by 46.3% of patients in the biologic-naive group and 29.0% in the biologic-inadequate group on the 200-mg regimen vs 18.0% and 6.4%, respectively, on placebo (P < .001 for both subgroups).

Sands noted that the drug has an excellent safety profile.

“These data show the drug works for naive patients who have failed conventional therapies, as well as for those who have failed biologic therapies,” so it could be used as a first- or second-line biologic, he added.

Sands reported potential conflicts of interest with AbbVie, Abivax, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, Artugen Therapeutics, AstraZeneca, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol-Myers Squibb, Calibr, Celgene, Celltrion, ClostraBio, Equillium, Enthera, Evommune, Ferring, Fresenius Kabi, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Janssen, Kaleido, Kallyope, Lilly, Merck, Microbiotica, Mobius Care, Morphic Therapeutic, MRM Health, Pfizer, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Pharma, Reistone Biopharma, Sun Pharma, Surrozen, Target RWE, Takeda, Teva, Theravance Biopharma, TLL Pharmaceutical, Tr1X, UNION Therapeutics, and Ventyx Biosciences.

A version of this article appeared on Medscape.com.

VIENNA — Guselkumab has been shown to be efficacious vs placebo in patients with moderately to severely active Crohn’s disease (CD), regardless of prior biologic therapy exposure, according to a pooled analysis of the two phase 3 double-blind GALAXI 2 and 3 studies.

“We found that guselkumab was effective in both biologic-naive and biologic-inadequate subpopulations,” said coinvestigator Bruce E. Sands, MD, AGAF, gastroenterologist from Icahn School of Medicine at Mount Sinai, New York City.

These latest results add to the primary results of these studies reported earlier in 2024 that guselkumab was shown to be superior to both placebo and ustekinumab in the same patient population with moderately to severely active CD.

Sands reported the new data in a presentation at the United European Gastroenterology (UEG) Week 2024.

Guselkumab potently blocks interleukin (IL)–23 and binds to CD64, a receptor on cells that produce IL-23. The dual-acting IL-23p19 subunit inhibitor agent is currently under review by the Food and Drug Administration (FDA) for moderately to severely active CD. In September, guselkumab (Tremfya, Johnson & Johnson) was approved for use in moderately to severely active ulcerative colitis.
 

GALAXI 2 and 3 Pooled Dataset

In the two independent, identically designed GALAXI 2 and 3 studies, patients were randomized to guselkumab treatment at either 200 mg intravenous (IV) induction at weeks 0, 4, and 8, followed by 200 mg subcutaneous maintenance every 4 weeks, starting at week 12, or 200 mg IV induction at weeks 0, 4, and 8, followed by 100 mg subcutaneous maintenance every 8 weeks, starting at week 16; or to ustekinumab; or to placebo.

Participants were required to remain on their treatment of initial randomization for a long-term extension study (up to 5 years) looking at clinical, endoscopic, and safety outcomes, except for participants on placebo who were allowed to switch to ustekinumab if clinical response was not met at week 12.

Inclusion criteria for the studies comprised a Crohn’s Disease Activity Index score between 220 and 450, a mean daily stool frequency count > 3 or an abdominal pain score > 1, and a simple endoscopic score for CD score ≥ 6. Participants were also required to have shown an inadequate response or intolerance to oral corticosteroids, 6-mercaptopurine/azathioprine/methotrexate, or biologic therapies.

The pooled dataset included patients on either dose of guselkumab and patients on placebo (total n = 730). Of these, 52% of participants had shown a prior inadequate response to a biologic, 42% were biologic naive, and 6% had prior exposure to biologics but no documented failure. Patients on ustekinumab were not included in this analysis.

Almost all patients (97%) in the biologic-inadequate response group had previously received at least one anti–tumor necrosis factor agent, and around 15% had received vedolizumab. As expected, the biologic-inadequate responders were a lot sicker than the biologic-naive patients, Sands reported.

The composite co–primary endpoints for each guselkumab regimen vs placebo were clinical response at week 12 plus clinical remission at week 48, and clinical response at week 12 plus endoscopic response at week 48.

The major secondary endpoints comprised clinical remission at week 12 and endoscopic response also at week 12.
 

Short- and Long-Term Endpoints in Both Subgroups

In the biologic-naive subgroup, 54.7% of patients receiving the 200-mg dose regimen of guselkumab and 51.7% of those receiving the 100-mg dose regimen showed a clinical response at week 12 plus clinical remission at week 48, compared with 11.5% in the placebo group (P < .001 for both compared with placebo).

In the biologic-inadequate response group, 49.7% of those receiving the 200-mg dose regimen of guselkumab and 45.8% on the 100-mg dose regimen reached the composite endpoint, compared with the placebo response of 12.8% (P < .001 for both compared with placebo).

“You can see a slight decrease in response in the biologic-inadequate responders, but on the whole, the confidence intervals are highly overlapping,” said Sands.

Turning to major secondary endpoints at week 12, clinical remission was reached by 49.6% of the biologic-naive group on the 200-mg guselkumab regimen vs 16.4% on placebo, and by 46.0% of the biologic-inadequate group on the 200-mg regimen vs 19.2% on placebo (P < .001 for both subgroups). Endoscopic response was achieved by 46.3% of patients in the biologic-naive group and 29.0% in the biologic-inadequate group on the 200-mg regimen vs 18.0% and 6.4%, respectively, on placebo (P < .001 for both subgroups).

Sands noted that the drug has an excellent safety profile.

“These data show the drug works for naive patients who have failed conventional therapies, as well as for those who have failed biologic therapies,” so it could be used as a first- or second-line biologic, he added.

Sands reported potential conflicts of interest with AbbVie, Abivax, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, Artugen Therapeutics, AstraZeneca, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol-Myers Squibb, Calibr, Celgene, Celltrion, ClostraBio, Equillium, Enthera, Evommune, Ferring, Fresenius Kabi, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Janssen, Kaleido, Kallyope, Lilly, Merck, Microbiotica, Mobius Care, Morphic Therapeutic, MRM Health, Pfizer, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Pharma, Reistone Biopharma, Sun Pharma, Surrozen, Target RWE, Takeda, Teva, Theravance Biopharma, TLL Pharmaceutical, Tr1X, UNION Therapeutics, and Ventyx Biosciences.

A version of this article appeared on Medscape.com.

VIENNA — Guselkumab has been shown to be efficacious vs placebo in patients with moderately to severely active Crohn’s disease (CD), regardless of prior biologic therapy exposure, according to a pooled analysis of the two phase 3 double-blind GALAXI 2 and 3 studies.

“We found that guselkumab was effective in both biologic-naive and biologic-inadequate subpopulations,” said coinvestigator Bruce E. Sands, MD, AGAF, gastroenterologist from Icahn School of Medicine at Mount Sinai, New York City.

These latest results add to the primary results of these studies reported earlier in 2024 that guselkumab was shown to be superior to both placebo and ustekinumab in the same patient population with moderately to severely active CD.

Sands reported the new data in a presentation at the United European Gastroenterology (UEG) Week 2024.

Guselkumab potently blocks interleukin (IL)–23 and binds to CD64, a receptor on cells that produce IL-23. The dual-acting IL-23p19 subunit inhibitor agent is currently under review by the Food and Drug Administration (FDA) for moderately to severely active CD. In September, guselkumab (Tremfya, Johnson & Johnson) was approved for use in moderately to severely active ulcerative colitis.
 

GALAXI 2 and 3 Pooled Dataset

In the two independent, identically designed GALAXI 2 and 3 studies, patients were randomized to guselkumab treatment at either 200 mg intravenous (IV) induction at weeks 0, 4, and 8, followed by 200 mg subcutaneous maintenance every 4 weeks, starting at week 12, or 200 mg IV induction at weeks 0, 4, and 8, followed by 100 mg subcutaneous maintenance every 8 weeks, starting at week 16; or to ustekinumab; or to placebo.

Participants were required to remain on their treatment of initial randomization for a long-term extension study (up to 5 years) looking at clinical, endoscopic, and safety outcomes, except for participants on placebo who were allowed to switch to ustekinumab if clinical response was not met at week 12.

Inclusion criteria for the studies comprised a Crohn’s Disease Activity Index score between 220 and 450, a mean daily stool frequency count > 3 or an abdominal pain score > 1, and a simple endoscopic score for CD score ≥ 6. Participants were also required to have shown an inadequate response or intolerance to oral corticosteroids, 6-mercaptopurine/azathioprine/methotrexate, or biologic therapies.

The pooled dataset included patients on either dose of guselkumab and patients on placebo (total n = 730). Of these, 52% of participants had shown a prior inadequate response to a biologic, 42% were biologic naive, and 6% had prior exposure to biologics but no documented failure. Patients on ustekinumab were not included in this analysis.

Almost all patients (97%) in the biologic-inadequate response group had previously received at least one anti–tumor necrosis factor agent, and around 15% had received vedolizumab. As expected, the biologic-inadequate responders were a lot sicker than the biologic-naive patients, Sands reported.

The composite co–primary endpoints for each guselkumab regimen vs placebo were clinical response at week 12 plus clinical remission at week 48, and clinical response at week 12 plus endoscopic response at week 48.

The major secondary endpoints comprised clinical remission at week 12 and endoscopic response also at week 12.
 

Short- and Long-Term Endpoints in Both Subgroups

In the biologic-naive subgroup, 54.7% of patients receiving the 200-mg dose regimen of guselkumab and 51.7% of those receiving the 100-mg dose regimen showed a clinical response at week 12 plus clinical remission at week 48, compared with 11.5% in the placebo group (P < .001 for both compared with placebo).

In the biologic-inadequate response group, 49.7% of those receiving the 200-mg dose regimen of guselkumab and 45.8% on the 100-mg dose regimen reached the composite endpoint, compared with the placebo response of 12.8% (P < .001 for both compared with placebo).

“You can see a slight decrease in response in the biologic-inadequate responders, but on the whole, the confidence intervals are highly overlapping,” said Sands.

Turning to major secondary endpoints at week 12, clinical remission was reached by 49.6% of the biologic-naive group on the 200-mg guselkumab regimen vs 16.4% on placebo, and by 46.0% of the biologic-inadequate group on the 200-mg regimen vs 19.2% on placebo (P < .001 for both subgroups). Endoscopic response was achieved by 46.3% of patients in the biologic-naive group and 29.0% in the biologic-inadequate group on the 200-mg regimen vs 18.0% and 6.4%, respectively, on placebo (P < .001 for both subgroups).

Sands noted that the drug has an excellent safety profile.

“These data show the drug works for naive patients who have failed conventional therapies, as well as for those who have failed biologic therapies,” so it could be used as a first- or second-line biologic, he added.

Sands reported potential conflicts of interest with AbbVie, Abivax, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, Artugen Therapeutics, AstraZeneca, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol-Myers Squibb, Calibr, Celgene, Celltrion, ClostraBio, Equillium, Enthera, Evommune, Ferring, Fresenius Kabi, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Janssen, Kaleido, Kallyope, Lilly, Merck, Microbiotica, Mobius Care, Morphic Therapeutic, MRM Health, Pfizer, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Pharma, Reistone Biopharma, Sun Pharma, Surrozen, Target RWE, Takeda, Teva, Theravance Biopharma, TLL Pharmaceutical, Tr1X, UNION Therapeutics, and Ventyx Biosciences.

A version of this article appeared on Medscape.com.

Irritable bowel syndrome (IBS) is one of the most common conditions encountered by both primary care providers and gastroenterologists, with a pooled global prevalence of 11.2%. This functional bowel disorder is characterized by abdominal pain or discomfort, diarrhea and/or constipation, and bloating.

Unfortunately, IBS is often misunderstood or minimized by some healthcare professionals, according to Alan Desmond, MB, consultant in gastroenterology and general internal medicine, Torbay Hospital, UK National Health Service.

Desmond regularly sees patients who either haven’t been accurately diagnosed or have been told, “Don’t worry, it’s ‘just’ irritable bowel syndrome,” he said at the recent International Conference on Nutrition in Medicine.

A 2017 study involving nearly 2000 patients with a history of gastrointestinal (GI) symptoms found that 43.1% of those who met the criteria for IBS were undiagnosed, and among those who were diagnosed, 26% were not receiving treatment.

“Many clinicians vastly underestimate the impact functional GI symptoms have on our patients in lack of productivity, becoming homebound or losing employment, the inability to enjoy a meal with friends or family, and always needing to know where the nearest bathroom is, for example,” Desmond said in an interview.

IBS can profoundly affect patients’ mental health. One study found that 38% of patients with IBS attending a tertiary care clinic contemplated suicide because they felt hopeless about ever achieving symptom relief.

Today, several dietary, pharmacologic, and psychological/behavioral approaches are available to treat patients with IBS, noted William D. Chey, MD, AGAF, chief of the Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan.

“Each individual patient may need a different combination of these foundational treatments,” he said. “One size doesn’t fit all.”
 

Diagnostic Pathway

One reason IBS is so hard to diagnose is that it’s a “symptom-based disorder, with identification of the condition predicated upon certain key characteristics that are heterogeneous,” Chey said in an interview. “IBS in patient ‘A’ may not present the same way as IBS in patient ‘B,’ although there are certain foundational common characteristics.”

IBS involves “abnormalities in the motility and contractility of the GI tract,” he said. It can present with diarrhea (IBS-D), constipation (IBS-C), or a mixture or alternation of diarrhea and constipation (IBS-M).

Patients with IBS-D often have an exaggerated gastro-colonic response, while those with IBS-C often have a blunted response.

Beyond stool abnormalities and abdominal pain/discomfort, patients often report bloating/distension, low backache, lethargy, nausea, thigh pain, and urinary and gynecologic symptoms.

Historically, IBS has been regarded as a “diagnosis of exclusion” because classic diagnostic tests typically yield no concrete findings. Desmond noted that several blood tests, procedures, imaging studies, and other tests are available to rule out other organic GI conditions, as outlined in the Table.

 

If the patient comes from a geographical region where giardia is endemic, clinicians also should consider testing for the parasite, Chey said.
 

New Understanding of IBS Etiology

Now, advances in the understanding of IBS are changing the approach to the disease.

“The field is moving away from seeing IBS as a ‘wastebasket diagnosis,’ recognizing that there are other causes of a patient’s symptoms,” Mark Pimentel, MD, associate professor of medicine and gastroenterology, Cedars-Sinai, Los Angeles, said in an interview. “What’s made IBS so difficult to diagnose has been the absence of biological markers and hallmark findings on endoscopy.”

Recent research points to novel bacterial causes as culprits in the development of IBS. In particular, altered small bowel microbiota can be triggered by acute gastroenteritis.

Food poisoning can trigger the onset of IBS — a phenomenon called “postinfectious IBS (PI-IBS),” said Pimentel, who is also executive director of the Medically Associated Science and Technology Program at Cedars-Sinai. PI-IBS almost always takes the form of IBS-D, with up to 60% of patients with IBS-D suffering the long-term sequelae of food poisoning.

The types of bacteria most commonly associated with gastroenteritis are Shigella, Campylobacter, Salmonella, and Escherichia coli, Pimentel said. All of them release cytolethal distending toxin B (CdtB), causing the body to produce antibodies to the toxin.

CdtB resembles vinculin, a naturally occurring protein critical for healthy gut function. “Because of this molecular resemblance, the immune system often mistakes one for the other, producing anti-vinculin,” Pimentel explained.

This autoimmune response leads to disruptions in the gut microbiome, ultimately resulting in PI-IBS. The chain of events “doesn’t necessarily happen immediately,” Pimentel said. “You might have developed food poisoning at a party weeks or months ago.”

Acute gastroenteritis is common, affecting as many as 179 million people in the United States annually. A meta-analysis of 47 studies, incorporating 28,270 patients, found that those who had experienced acute gastroenteritis had a fourfold higher risk of developing IBS compared with nonexposed controls.

“The problem isn’t only the IBS itself, but the fact that people with PI-IBS are four times as likely to contract food poisoning again, which can further exacerbate IBS symptoms,” Pimentel said.

Diarrhea-predominant IBS can be detected through the presence of two blood biomarkers — anti-CdtB and anti-vinculin — in a blood test developed by Pimentel and his group.

“Elevation in either of these biomarkers establishes the diagnosis,” Pimentel said. “This is a breakthrough because it represents the first test that can make IBS a ‘diagnosis of inclusion.’”

The blood test also can identify IBS-M but not IBS-C.

Pimentel said that IBS-C is associated with increased levels of methanogenic archaea, which can be diagnosed by a positive methane breath test. “Methane gas slows intestinal contractility, which might result in constipation,” he said.
 

Diet as a Treatment Option

Diet is usually the starting point for IBS treatment, Chey said. “The standard dietary recommendations, as defined by the National Institute for Health and Care Excellence Guidance for managing IBS, are reasonable and common sense — eating three meals a day, avoiding carbonated beverages, excess alcohol, and excess caffeine, and avoiding hard-to-digest foods that can be gas producing.”

A diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), which are carbohydrates that aren’t completely absorbed in the intestines, has been shown to be effective in alleviating GI distress in as many as 86% of patients with IBS, leading to improvements in overall GI symptoms as well as individual symptoms (eg, abdominal pain, bloating, constipation, diarrhea, and flatulence).

Desmond recommends the low FODMAP program delineated by Monash University in Australia. The diet should be undertaken only under the supervision of a dietitian, he warned. Moreover, following it on a long-term basis can have an adverse impact on dietary quality and the gut microbiome. Therefore, “it’s important to embark on stepwise reintroduction of FODMAPS under supervision to find acceptable thresholds that don’t cause a return of symptoms.”

A growing body of research suggests that following the Mediterranean diet can be helpful in reducing IBS symptoms. Chey said that some patients who tend to over-restrict their eating might benefit from a less restrictive diet than the typical low FODMAPs diet. For them, the Mediterranean diet may be a good option.
 

Pharmacotherapy for IBS

Nutritional approaches aren’t for everyone, Chey noted. “Some people don’t want to be on a highly restricted diet.” For them, medications addressing symptoms might be a better option.

Antispasmodics — either anticholinergics (hyoscine and dicyclomine) or smooth muscle relaxants (alverine, mebeverine, and peppermint oil) — can be helpful, although they can worsen constipation in a dose-dependent manner. It is advisable to use them on an as-needed rather than long-term basis.

Antidiarrheal agents include loperamide and diphenoxylate.

For constipation, laxatives (eg, senna, bisacodyl, polyethylene glycol, and sodium picosulfate) can be helpful.

Desmond noted that the American Gastroenterological Association does not recommend routine use of probiotics for most GI disorders, including IBS. Exceptions include prevention of Clostridioides difficile, ulcerative colitis, and pouchitis.
 

Targeting the Gut-Brain Relationship

Stress plays a role in exacerbating symptoms in patients with IBS and is an important target for intervention.

“If patients are living with a level of stress that’s impairing, we won’t be able to solve their gut issues until we resolve their stress issues,” Desmond said. “We need to calm the gut-microbiome-brain axis, which is multidimensional and bidirectional.”

Many people — even those without IBS — experience queasiness or diarrhea prior to a major event they’re nervous about, Chey noted. These events activate the brain, which activates the nervous system, which interacts with the GI tract. Indeed, IBS is now recognized as a disorder of gut-brain interaction, he said.

“We now know that the microbiome in the GI tract influences cognition and emotional function, depression, and anxiety. One might say that the gut is the ‘center of the universe’ to human beings,” Chey said.

Evidence-based psychological approaches for stress reduction in patients with IBS include cognitive behavioral therapy, specifically tailored to helping the patient identify associations between IBS symptoms and thoughts, emotions, and actions, as well as learning new behaviors and engaging in stress management. Psychodynamic (interpersonal) therapy enables patients to understand the connection between GI symptoms and interpersonal conflicts, emotional factors, or relationship difficulties.

Gut-directed hypnotherapy (GDH) is a “proven modality for IBS,” Desmond said. Unlike other forms of hypnotherapy, GDH focuses specifically on controlling and normalizing GI function. Studies have shown a reduction of ≥ 30% in abdominal pain in two thirds of participants, with overall response rates up to 85%. It can be delivered in an individual or group setting or via a smartphone.

Desmond recommends mindfulness-based therapy (MBT) for IBS. MBT focuses on the “cultivation of mindfulness, defined as intentional, nonjudgmental, present-focused awareness.” It has been found effective in reducing flares and the markers of gut inflammation in ulcerative colitis, as well as reducing symptoms of IBS.

Chey noted that an emerging body of literature supports the potential role of acupuncture in treating IBS, and his clinic employs it. “I would like to see further research into other areas of CAM [complementary and alternative medicine], including herbal approaches to IBS symptoms as well as stress.”

Finally, all the experts agree that more research is needed.

“The real tragedy is that the NIH invests next to nothing in IBS, in contrast to inflammatory bowel disease and many other conditions,” Pimentel said. “Yet IBS is 45 times more common than inflammatory bowel disease.”

Pimentel hopes that with enough advocacy and recognition that IBS isn’t “just stress-related,” more resources will be devoted to understanding this debilitating condition.

Desmond is the author of a book on the benefits of a plant-based diet. He has also received honoraria, speaking, and consultancy fees from the European Space Agency, Dyson Institute of Engineering and Technology, Riverford Organic Farmers, Ltd., Salesforce Inc., Sentara Healthcare, Saudi Sports for All Federation, the Physicians Committee for Responsible Medicine, The Plantrician Project, Doctors for Nutrition, and The Happy Pear.

Pimentel is a consultant for Bausch Health, Ferring Pharmaceuticals, and Ardelyx. He holds equity in and is also a consultant for Dieta Health, Salvo Health, Cylinder Health, and Gemelli Biotech. Cedars-Sinai has a licensing agreement with Gemelli Biotech and Hobbs Medical.

Chey is a consultant to AbbVie, Ardelyx, Atmo, Biomerica, Gemelli Biotech, Ironwood Pharmaceuticals, Nestlé, QOL Medical, Phathom Pharmaceuticals, Redhill, Salix/Valeant, Takeda, and Vibrant. He receives grant/research funding from Commonwealth Diagnostics International, Inc., US Food and Drug Administration, National Institutes of Health, QOL Medical, and Salix/Valeant. He holds stock options in Coprata, Dieta Health, Evinature, FoodMarble, Kiwi Biosciences, and ModifyHealth. He is a board or advisory panel member of the American College of Gastroenterology, GI Health Foundation, International Foundation for Gastrointestinal Disorders, Rome. He holds patents on My Nutrition Health, Digital Manometry, and Rectal Expulsion Device.

A version of this article appeared on Medscape.com.

Irritable bowel syndrome (IBS) is one of the most common conditions encountered by both primary care providers and gastroenterologists, with a pooled global prevalence of 11.2%. This functional bowel disorder is characterized by abdominal pain or discomfort, diarrhea and/or constipation, and bloating.

Unfortunately, IBS is often misunderstood or minimized by some healthcare professionals, according to Alan Desmond, MB, consultant in gastroenterology and general internal medicine, Torbay Hospital, UK National Health Service.

Desmond regularly sees patients who either haven’t been accurately diagnosed or have been told, “Don’t worry, it’s ‘just’ irritable bowel syndrome,” he said at the recent International Conference on Nutrition in Medicine.

A 2017 study involving nearly 2000 patients with a history of gastrointestinal (GI) symptoms found that 43.1% of those who met the criteria for IBS were undiagnosed, and among those who were diagnosed, 26% were not receiving treatment.

“Many clinicians vastly underestimate the impact functional GI symptoms have on our patients in lack of productivity, becoming homebound or losing employment, the inability to enjoy a meal with friends or family, and always needing to know where the nearest bathroom is, for example,” Desmond said in an interview.

IBS can profoundly affect patients’ mental health. One study found that 38% of patients with IBS attending a tertiary care clinic contemplated suicide because they felt hopeless about ever achieving symptom relief.

Today, several dietary, pharmacologic, and psychological/behavioral approaches are available to treat patients with IBS, noted William D. Chey, MD, AGAF, chief of the Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan.

“Each individual patient may need a different combination of these foundational treatments,” he said. “One size doesn’t fit all.”
 

Diagnostic Pathway

One reason IBS is so hard to diagnose is that it’s a “symptom-based disorder, with identification of the condition predicated upon certain key characteristics that are heterogeneous,” Chey said in an interview. “IBS in patient ‘A’ may not present the same way as IBS in patient ‘B,’ although there are certain foundational common characteristics.”

IBS involves “abnormalities in the motility and contractility of the GI tract,” he said. It can present with diarrhea (IBS-D), constipation (IBS-C), or a mixture or alternation of diarrhea and constipation (IBS-M).

Patients with IBS-D often have an exaggerated gastro-colonic response, while those with IBS-C often have a blunted response.

Beyond stool abnormalities and abdominal pain/discomfort, patients often report bloating/distension, low backache, lethargy, nausea, thigh pain, and urinary and gynecologic symptoms.

Historically, IBS has been regarded as a “diagnosis of exclusion” because classic diagnostic tests typically yield no concrete findings. Desmond noted that several blood tests, procedures, imaging studies, and other tests are available to rule out other organic GI conditions, as outlined in the Table.

 

If the patient comes from a geographical region where giardia is endemic, clinicians also should consider testing for the parasite, Chey said.
 

New Understanding of IBS Etiology

Now, advances in the understanding of IBS are changing the approach to the disease.

“The field is moving away from seeing IBS as a ‘wastebasket diagnosis,’ recognizing that there are other causes of a patient’s symptoms,” Mark Pimentel, MD, associate professor of medicine and gastroenterology, Cedars-Sinai, Los Angeles, said in an interview. “What’s made IBS so difficult to diagnose has been the absence of biological markers and hallmark findings on endoscopy.”

Recent research points to novel bacterial causes as culprits in the development of IBS. In particular, altered small bowel microbiota can be triggered by acute gastroenteritis.

Food poisoning can trigger the onset of IBS — a phenomenon called “postinfectious IBS (PI-IBS),” said Pimentel, who is also executive director of the Medically Associated Science and Technology Program at Cedars-Sinai. PI-IBS almost always takes the form of IBS-D, with up to 60% of patients with IBS-D suffering the long-term sequelae of food poisoning.

The types of bacteria most commonly associated with gastroenteritis are Shigella, Campylobacter, Salmonella, and Escherichia coli, Pimentel said. All of them release cytolethal distending toxin B (CdtB), causing the body to produce antibodies to the toxin.

CdtB resembles vinculin, a naturally occurring protein critical for healthy gut function. “Because of this molecular resemblance, the immune system often mistakes one for the other, producing anti-vinculin,” Pimentel explained.

This autoimmune response leads to disruptions in the gut microbiome, ultimately resulting in PI-IBS. The chain of events “doesn’t necessarily happen immediately,” Pimentel said. “You might have developed food poisoning at a party weeks or months ago.”

Acute gastroenteritis is common, affecting as many as 179 million people in the United States annually. A meta-analysis of 47 studies, incorporating 28,270 patients, found that those who had experienced acute gastroenteritis had a fourfold higher risk of developing IBS compared with nonexposed controls.

“The problem isn’t only the IBS itself, but the fact that people with PI-IBS are four times as likely to contract food poisoning again, which can further exacerbate IBS symptoms,” Pimentel said.

Diarrhea-predominant IBS can be detected through the presence of two blood biomarkers — anti-CdtB and anti-vinculin — in a blood test developed by Pimentel and his group.

“Elevation in either of these biomarkers establishes the diagnosis,” Pimentel said. “This is a breakthrough because it represents the first test that can make IBS a ‘diagnosis of inclusion.’”

The blood test also can identify IBS-M but not IBS-C.

Pimentel said that IBS-C is associated with increased levels of methanogenic archaea, which can be diagnosed by a positive methane breath test. “Methane gas slows intestinal contractility, which might result in constipation,” he said.
 

Diet as a Treatment Option

Diet is usually the starting point for IBS treatment, Chey said. “The standard dietary recommendations, as defined by the National Institute for Health and Care Excellence Guidance for managing IBS, are reasonable and common sense — eating three meals a day, avoiding carbonated beverages, excess alcohol, and excess caffeine, and avoiding hard-to-digest foods that can be gas producing.”

A diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), which are carbohydrates that aren’t completely absorbed in the intestines, has been shown to be effective in alleviating GI distress in as many as 86% of patients with IBS, leading to improvements in overall GI symptoms as well as individual symptoms (eg, abdominal pain, bloating, constipation, diarrhea, and flatulence).

Desmond recommends the low FODMAP program delineated by Monash University in Australia. The diet should be undertaken only under the supervision of a dietitian, he warned. Moreover, following it on a long-term basis can have an adverse impact on dietary quality and the gut microbiome. Therefore, “it’s important to embark on stepwise reintroduction of FODMAPS under supervision to find acceptable thresholds that don’t cause a return of symptoms.”

A growing body of research suggests that following the Mediterranean diet can be helpful in reducing IBS symptoms. Chey said that some patients who tend to over-restrict their eating might benefit from a less restrictive diet than the typical low FODMAPs diet. For them, the Mediterranean diet may be a good option.
 

Pharmacotherapy for IBS

Nutritional approaches aren’t for everyone, Chey noted. “Some people don’t want to be on a highly restricted diet.” For them, medications addressing symptoms might be a better option.

Antispasmodics — either anticholinergics (hyoscine and dicyclomine) or smooth muscle relaxants (alverine, mebeverine, and peppermint oil) — can be helpful, although they can worsen constipation in a dose-dependent manner. It is advisable to use them on an as-needed rather than long-term basis.

Antidiarrheal agents include loperamide and diphenoxylate.

For constipation, laxatives (eg, senna, bisacodyl, polyethylene glycol, and sodium picosulfate) can be helpful.

Desmond noted that the American Gastroenterological Association does not recommend routine use of probiotics for most GI disorders, including IBS. Exceptions include prevention of Clostridioides difficile, ulcerative colitis, and pouchitis.
 

Targeting the Gut-Brain Relationship

Stress plays a role in exacerbating symptoms in patients with IBS and is an important target for intervention.

“If patients are living with a level of stress that’s impairing, we won’t be able to solve their gut issues until we resolve their stress issues,” Desmond said. “We need to calm the gut-microbiome-brain axis, which is multidimensional and bidirectional.”

Many people — even those without IBS — experience queasiness or diarrhea prior to a major event they’re nervous about, Chey noted. These events activate the brain, which activates the nervous system, which interacts with the GI tract. Indeed, IBS is now recognized as a disorder of gut-brain interaction, he said.

“We now know that the microbiome in the GI tract influences cognition and emotional function, depression, and anxiety. One might say that the gut is the ‘center of the universe’ to human beings,” Chey said.

Evidence-based psychological approaches for stress reduction in patients with IBS include cognitive behavioral therapy, specifically tailored to helping the patient identify associations between IBS symptoms and thoughts, emotions, and actions, as well as learning new behaviors and engaging in stress management. Psychodynamic (interpersonal) therapy enables patients to understand the connection between GI symptoms and interpersonal conflicts, emotional factors, or relationship difficulties.

Gut-directed hypnotherapy (GDH) is a “proven modality for IBS,” Desmond said. Unlike other forms of hypnotherapy, GDH focuses specifically on controlling and normalizing GI function. Studies have shown a reduction of ≥ 30% in abdominal pain in two thirds of participants, with overall response rates up to 85%. It can be delivered in an individual or group setting or via a smartphone.

Desmond recommends mindfulness-based therapy (MBT) for IBS. MBT focuses on the “cultivation of mindfulness, defined as intentional, nonjudgmental, present-focused awareness.” It has been found effective in reducing flares and the markers of gut inflammation in ulcerative colitis, as well as reducing symptoms of IBS.

Chey noted that an emerging body of literature supports the potential role of acupuncture in treating IBS, and his clinic employs it. “I would like to see further research into other areas of CAM [complementary and alternative medicine], including herbal approaches to IBS symptoms as well as stress.”

Finally, all the experts agree that more research is needed.

“The real tragedy is that the NIH invests next to nothing in IBS, in contrast to inflammatory bowel disease and many other conditions,” Pimentel said. “Yet IBS is 45 times more common than inflammatory bowel disease.”

Pimentel hopes that with enough advocacy and recognition that IBS isn’t “just stress-related,” more resources will be devoted to understanding this debilitating condition.

Desmond is the author of a book on the benefits of a plant-based diet. He has also received honoraria, speaking, and consultancy fees from the European Space Agency, Dyson Institute of Engineering and Technology, Riverford Organic Farmers, Ltd., Salesforce Inc., Sentara Healthcare, Saudi Sports for All Federation, the Physicians Committee for Responsible Medicine, The Plantrician Project, Doctors for Nutrition, and The Happy Pear.

Pimentel is a consultant for Bausch Health, Ferring Pharmaceuticals, and Ardelyx. He holds equity in and is also a consultant for Dieta Health, Salvo Health, Cylinder Health, and Gemelli Biotech. Cedars-Sinai has a licensing agreement with Gemelli Biotech and Hobbs Medical.

Chey is a consultant to AbbVie, Ardelyx, Atmo, Biomerica, Gemelli Biotech, Ironwood Pharmaceuticals, Nestlé, QOL Medical, Phathom Pharmaceuticals, Redhill, Salix/Valeant, Takeda, and Vibrant. He receives grant/research funding from Commonwealth Diagnostics International, Inc., US Food and Drug Administration, National Institutes of Health, QOL Medical, and Salix/Valeant. He holds stock options in Coprata, Dieta Health, Evinature, FoodMarble, Kiwi Biosciences, and ModifyHealth. He is a board or advisory panel member of the American College of Gastroenterology, GI Health Foundation, International Foundation for Gastrointestinal Disorders, Rome. He holds patents on My Nutrition Health, Digital Manometry, and Rectal Expulsion Device.

A version of this article appeared on Medscape.com.

Irritable bowel syndrome (IBS) is one of the most common conditions encountered by both primary care providers and gastroenterologists, with a pooled global prevalence of 11.2%. This functional bowel disorder is characterized by abdominal pain or discomfort, diarrhea and/or constipation, and bloating.

Unfortunately, IBS is often misunderstood or minimized by some healthcare professionals, according to Alan Desmond, MB, consultant in gastroenterology and general internal medicine, Torbay Hospital, UK National Health Service.

Desmond regularly sees patients who either haven’t been accurately diagnosed or have been told, “Don’t worry, it’s ‘just’ irritable bowel syndrome,” he said at the recent International Conference on Nutrition in Medicine.

A 2017 study involving nearly 2000 patients with a history of gastrointestinal (GI) symptoms found that 43.1% of those who met the criteria for IBS were undiagnosed, and among those who were diagnosed, 26% were not receiving treatment.

“Many clinicians vastly underestimate the impact functional GI symptoms have on our patients in lack of productivity, becoming homebound or losing employment, the inability to enjoy a meal with friends or family, and always needing to know where the nearest bathroom is, for example,” Desmond said in an interview.

IBS can profoundly affect patients’ mental health. One study found that 38% of patients with IBS attending a tertiary care clinic contemplated suicide because they felt hopeless about ever achieving symptom relief.

Today, several dietary, pharmacologic, and psychological/behavioral approaches are available to treat patients with IBS, noted William D. Chey, MD, AGAF, chief of the Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan.

“Each individual patient may need a different combination of these foundational treatments,” he said. “One size doesn’t fit all.”
 

Diagnostic Pathway

One reason IBS is so hard to diagnose is that it’s a “symptom-based disorder, with identification of the condition predicated upon certain key characteristics that are heterogeneous,” Chey said in an interview. “IBS in patient ‘A’ may not present the same way as IBS in patient ‘B,’ although there are certain foundational common characteristics.”

IBS involves “abnormalities in the motility and contractility of the GI tract,” he said. It can present with diarrhea (IBS-D), constipation (IBS-C), or a mixture or alternation of diarrhea and constipation (IBS-M).

Patients with IBS-D often have an exaggerated gastro-colonic response, while those with IBS-C often have a blunted response.

Beyond stool abnormalities and abdominal pain/discomfort, patients often report bloating/distension, low backache, lethargy, nausea, thigh pain, and urinary and gynecologic symptoms.

Historically, IBS has been regarded as a “diagnosis of exclusion” because classic diagnostic tests typically yield no concrete findings. Desmond noted that several blood tests, procedures, imaging studies, and other tests are available to rule out other organic GI conditions, as outlined in the Table.

 

If the patient comes from a geographical region where giardia is endemic, clinicians also should consider testing for the parasite, Chey said.
 

New Understanding of IBS Etiology

Now, advances in the understanding of IBS are changing the approach to the disease.

“The field is moving away from seeing IBS as a ‘wastebasket diagnosis,’ recognizing that there are other causes of a patient’s symptoms,” Mark Pimentel, MD, associate professor of medicine and gastroenterology, Cedars-Sinai, Los Angeles, said in an interview. “What’s made IBS so difficult to diagnose has been the absence of biological markers and hallmark findings on endoscopy.”

Recent research points to novel bacterial causes as culprits in the development of IBS. In particular, altered small bowel microbiota can be triggered by acute gastroenteritis.

Food poisoning can trigger the onset of IBS — a phenomenon called “postinfectious IBS (PI-IBS),” said Pimentel, who is also executive director of the Medically Associated Science and Technology Program at Cedars-Sinai. PI-IBS almost always takes the form of IBS-D, with up to 60% of patients with IBS-D suffering the long-term sequelae of food poisoning.

The types of bacteria most commonly associated with gastroenteritis are Shigella, Campylobacter, Salmonella, and Escherichia coli, Pimentel said. All of them release cytolethal distending toxin B (CdtB), causing the body to produce antibodies to the toxin.

CdtB resembles vinculin, a naturally occurring protein critical for healthy gut function. “Because of this molecular resemblance, the immune system often mistakes one for the other, producing anti-vinculin,” Pimentel explained.

This autoimmune response leads to disruptions in the gut microbiome, ultimately resulting in PI-IBS. The chain of events “doesn’t necessarily happen immediately,” Pimentel said. “You might have developed food poisoning at a party weeks or months ago.”

Acute gastroenteritis is common, affecting as many as 179 million people in the United States annually. A meta-analysis of 47 studies, incorporating 28,270 patients, found that those who had experienced acute gastroenteritis had a fourfold higher risk of developing IBS compared with nonexposed controls.

“The problem isn’t only the IBS itself, but the fact that people with PI-IBS are four times as likely to contract food poisoning again, which can further exacerbate IBS symptoms,” Pimentel said.

Diarrhea-predominant IBS can be detected through the presence of two blood biomarkers — anti-CdtB and anti-vinculin — in a blood test developed by Pimentel and his group.

“Elevation in either of these biomarkers establishes the diagnosis,” Pimentel said. “This is a breakthrough because it represents the first test that can make IBS a ‘diagnosis of inclusion.’”

The blood test also can identify IBS-M but not IBS-C.

Pimentel said that IBS-C is associated with increased levels of methanogenic archaea, which can be diagnosed by a positive methane breath test. “Methane gas slows intestinal contractility, which might result in constipation,” he said.
 

Diet as a Treatment Option

Diet is usually the starting point for IBS treatment, Chey said. “The standard dietary recommendations, as defined by the National Institute for Health and Care Excellence Guidance for managing IBS, are reasonable and common sense — eating three meals a day, avoiding carbonated beverages, excess alcohol, and excess caffeine, and avoiding hard-to-digest foods that can be gas producing.”

A diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), which are carbohydrates that aren’t completely absorbed in the intestines, has been shown to be effective in alleviating GI distress in as many as 86% of patients with IBS, leading to improvements in overall GI symptoms as well as individual symptoms (eg, abdominal pain, bloating, constipation, diarrhea, and flatulence).

Desmond recommends the low FODMAP program delineated by Monash University in Australia. The diet should be undertaken only under the supervision of a dietitian, he warned. Moreover, following it on a long-term basis can have an adverse impact on dietary quality and the gut microbiome. Therefore, “it’s important to embark on stepwise reintroduction of FODMAPS under supervision to find acceptable thresholds that don’t cause a return of symptoms.”

A growing body of research suggests that following the Mediterranean diet can be helpful in reducing IBS symptoms. Chey said that some patients who tend to over-restrict their eating might benefit from a less restrictive diet than the typical low FODMAPs diet. For them, the Mediterranean diet may be a good option.
 

Pharmacotherapy for IBS

Nutritional approaches aren’t for everyone, Chey noted. “Some people don’t want to be on a highly restricted diet.” For them, medications addressing symptoms might be a better option.

Antispasmodics — either anticholinergics (hyoscine and dicyclomine) or smooth muscle relaxants (alverine, mebeverine, and peppermint oil) — can be helpful, although they can worsen constipation in a dose-dependent manner. It is advisable to use them on an as-needed rather than long-term basis.

Antidiarrheal agents include loperamide and diphenoxylate.

For constipation, laxatives (eg, senna, bisacodyl, polyethylene glycol, and sodium picosulfate) can be helpful.

Desmond noted that the American Gastroenterological Association does not recommend routine use of probiotics for most GI disorders, including IBS. Exceptions include prevention of Clostridioides difficile, ulcerative colitis, and pouchitis.
 

Targeting the Gut-Brain Relationship

Stress plays a role in exacerbating symptoms in patients with IBS and is an important target for intervention.

“If patients are living with a level of stress that’s impairing, we won’t be able to solve their gut issues until we resolve their stress issues,” Desmond said. “We need to calm the gut-microbiome-brain axis, which is multidimensional and bidirectional.”

Many people — even those without IBS — experience queasiness or diarrhea prior to a major event they’re nervous about, Chey noted. These events activate the brain, which activates the nervous system, which interacts with the GI tract. Indeed, IBS is now recognized as a disorder of gut-brain interaction, he said.

“We now know that the microbiome in the GI tract influences cognition and emotional function, depression, and anxiety. One might say that the gut is the ‘center of the universe’ to human beings,” Chey said.

Evidence-based psychological approaches for stress reduction in patients with IBS include cognitive behavioral therapy, specifically tailored to helping the patient identify associations between IBS symptoms and thoughts, emotions, and actions, as well as learning new behaviors and engaging in stress management. Psychodynamic (interpersonal) therapy enables patients to understand the connection between GI symptoms and interpersonal conflicts, emotional factors, or relationship difficulties.

Gut-directed hypnotherapy (GDH) is a “proven modality for IBS,” Desmond said. Unlike other forms of hypnotherapy, GDH focuses specifically on controlling and normalizing GI function. Studies have shown a reduction of ≥ 30% in abdominal pain in two thirds of participants, with overall response rates up to 85%. It can be delivered in an individual or group setting or via a smartphone.

Desmond recommends mindfulness-based therapy (MBT) for IBS. MBT focuses on the “cultivation of mindfulness, defined as intentional, nonjudgmental, present-focused awareness.” It has been found effective in reducing flares and the markers of gut inflammation in ulcerative colitis, as well as reducing symptoms of IBS.

Chey noted that an emerging body of literature supports the potential role of acupuncture in treating IBS, and his clinic employs it. “I would like to see further research into other areas of CAM [complementary and alternative medicine], including herbal approaches to IBS symptoms as well as stress.”

Finally, all the experts agree that more research is needed.

“The real tragedy is that the NIH invests next to nothing in IBS, in contrast to inflammatory bowel disease and many other conditions,” Pimentel said. “Yet IBS is 45 times more common than inflammatory bowel disease.”

Pimentel hopes that with enough advocacy and recognition that IBS isn’t “just stress-related,” more resources will be devoted to understanding this debilitating condition.

Desmond is the author of a book on the benefits of a plant-based diet. He has also received honoraria, speaking, and consultancy fees from the European Space Agency, Dyson Institute of Engineering and Technology, Riverford Organic Farmers, Ltd., Salesforce Inc., Sentara Healthcare, Saudi Sports for All Federation, the Physicians Committee for Responsible Medicine, The Plantrician Project, Doctors for Nutrition, and The Happy Pear.

Pimentel is a consultant for Bausch Health, Ferring Pharmaceuticals, and Ardelyx. He holds equity in and is also a consultant for Dieta Health, Salvo Health, Cylinder Health, and Gemelli Biotech. Cedars-Sinai has a licensing agreement with Gemelli Biotech and Hobbs Medical.

Chey is a consultant to AbbVie, Ardelyx, Atmo, Biomerica, Gemelli Biotech, Ironwood Pharmaceuticals, Nestlé, QOL Medical, Phathom Pharmaceuticals, Redhill, Salix/Valeant, Takeda, and Vibrant. He receives grant/research funding from Commonwealth Diagnostics International, Inc., US Food and Drug Administration, National Institutes of Health, QOL Medical, and Salix/Valeant. He holds stock options in Coprata, Dieta Health, Evinature, FoodMarble, Kiwi Biosciences, and ModifyHealth. He is a board or advisory panel member of the American College of Gastroenterology, GI Health Foundation, International Foundation for Gastrointestinal Disorders, Rome. He holds patents on My Nutrition Health, Digital Manometry, and Rectal Expulsion Device.

A version of this article appeared on Medscape.com.