DAY 3 - Highlights of the 2025 AGA Clinical Guidelines and an Invitation to Comment

Siddharth Singh, MD, from the University of California San Diego in California, and Chair of the AGA guidelines committee, reviewed the IOM-based framework used to develop trustworthy clinical practice guidelines, which prioritizes transparency, management of conflicts of interest, rigorous systematic review of available evidence to judge the strength of each recommendation, and articulation of recommendations with external reviewers. He described the use of the GRADE process to identify questions of interest, review the literature, and conduct an evidence-to-decision process to assess net benefits and harms, the certainty of evidence, value to patients, resource use (cost), health equity, acceptability, and feasibility. Recommendations are presented as strong or conditional based on patient, clinician, and policy maker perspectives. 

Perica Davitkov, MD, from VA Medical Center in Cleveland, Ohio, and Sachin B. Wani, MD, from the University of Colorado in Aurora, Colorado, covered recommendations for surveillance and dysplasia detection in Barrett’s esophagus, which replaces document published in 2011. Surveillance is crucial to prevent esophageal adenocarcinoma and permit early intervention to improve outcomes, but the frequency of surveillance is unclear. The new guidelines emphasize the importance of high-quality endoscopy and thorough analysis using standardized classification systems. Their literature review led to the following recommendations:

•    Surveillance every 3 years; the interval can be extended to 5 years or discontinued in certain patients
•    Surveillance should include a combination of HD white light and chromoendoscopy 
•    Seattle biopsy protocol should be followed
The new guidelines provide no recommendation for or against the routine use of advanced sampling techniques or use of biomarkers (e.g., p53 staining and TissueCypher) to predict progression to high-grade dysplasia and cancer. These areas are recognized as knowledge gap, with limited data on how these practices impact patient care. 
Additional recommendations included the referral of patients with confirmed Barrett’s-related neoplasia to specialized centers for surveillance, and the use of PPIs to prevent progression to high-grade dysplasia or cancer.

Dr. Singh joined Frank I. Scott, MD, from the University of Colorado Anschutz Medical Campus in Aurora, Colorado, to discuss the AGA living guidelines on the pharmacologic management of moderate to severe Crohn’s disease (CD), which are reviewed every 6 months as new treatments and new data emerge. The most recent living guideline for ulcerative colitis was published in November of 2024. They emphasized that the guideline recommendations are limited to adults with moderately to severely active CD in the ambulatory setting; confirmation of active disease should be made prior to starting AT, retreatment screening and vaccination is important, and after initiation, patients should be monitored for response and toxicity. Nine new clinical questions and evidence-based recommendations are included in the new guidelines, and Drs. Singh and Scott focused on three:

1)    What is the efficacy of advanced therapies (AT) for induction and maintenance? TNF antagonists, IL-12/23 antagonists, IL-23p19 antagonists, and JAK inhibitors were compared to no treatment for the outcomes of induction and maintenance of clinical remission with 10% improvement as the clinically important threshold. Based on the analysis, AGA recommends for adult outpatients with moderately to severely active CD: infliximab, adalimumab, ustekinumab, risankizumab, mirikizumab, guselkumab, or upadactinib over no treatment and suggests use of certolizumab pegol or vedolizumab over no treatment. Other considerations: biosimilars can be considered, subcutaneous administration has shown comparable efficacy to IV, extended induction or dose escalation may be required for some patients, and higher dosing of maintenance may be required for some patients who are treatment refractory.
2)    In patients naïve to AT, what is the comparative efficacy of AT? A network meta-analysis was performed to compare AT, with an absolute risk difference threshold of 5% indicating improvement over the comparator for outcomes. AT were classified as higher or lower efficacy. Higher efficacy medications in naïve patients were infliximab, adalimumab, vedolizumab, ustekinumab, risankizumab, mirikizumab, and guselkumab. Lower efficacy medications for naïve patients were certolizumab pegol and upadacitinib. FDA recommends reserving the use of JAK inhibitors for patients with failure or intolerance to anti-TNF therapy. Individual patient factors and preferences should be considered when selecting an AT.

3)    In patients exposed to AT, what is the comparative efficacy of AT? The vast majority of patients in the reviewed studies had been exposed to anti-TNF therapies. Again, a network meta-analysis was conducted to classify AT into higher, intermediate, and low efficacy groups.  Higher efficacy AT were adalimumab, risankizumab, guselkumab, and upadacitinib; intermediate efficacy AT were ustekinumab and mirikizumab; and lower efficacy AT were certolizumab pegol and vedolizumab. It is important to consider the cardiovascular risks associated with JAK inhibitors, and second-line anti-TNF may be effective in patients who have failed an anti-TNF, unless they have primary refractory disease. 

Knowledge gaps remain in the areas of immunomodulation monotherapy and in combination with other TAs, de-escalation of therapy, and the relative efficacy of step-up and top-down approaches.

Osama Altayar, MD, from Washington University in St. Louis, Missouri, and Michael Camilleri, MD, from Mayo Clinic College of Medicine in Rochester, Minnesota, reviewed the AGA guideline recommendations for the management of gastroparesis, a motility disorder characterized by delayed gastric emptying with symptoms of at least 3 months. Gastroparesis leads to more than 140,000 outpatient visits annually but only one agent (metoclopramide) has been approved by the FDA. The guidelines committee considered the evidence related to 12 clinical questions, and used efficacy thresholds based on Minimally Clinically Important Difference (MCID – the smallest change that can be perceived by patients) of the Gastroparesis-Cardinal Symptom Index – Daily Diary (GCSI-DD) for each symptom of gastroparesis (e.g., nausea, vomiting). Most of the recommendations were conditional based on low or very low certainty of evidence, indicating that physicians should provide information to patients to support shared decision-making, which may include no treatment. The recommendations were:

•    The gastric emptying study should be more than 2 hours and preferably 4 hours for diagnosis of suspected gastroparesis
•    Metoclopramide is recommended over no treatment, but side effects should be discussed, particularly for patients taking psychotropic medications and older patients, and side effects should be evaluated at 4-8 weeks to determine whether to continue treatment
•    Erythromycin is recommended over no treatment
•    Domperidone is not recommended, but may be helpful for those with neurological side effects or movement disorders and cant take metoclopramide. But this drug is no longer being made.
•    Prucalopride is not recommended but may be useful for patients with chronic idiopathic constipation.
•    NK-1 receptor antagonists, the neuromodulators nortriptyline and buspirone, and cannabinoids are not recommended.
•    G-POEM is not recommended, except in selected patents with medically refractory disease (see Malik et al. Gastrointest Endosc. 2025).
•    Surgical pyloric interventions are not recommended except in the context of a clinical trial. This area was identified as a knowledge gap.
•    Botulinum toxin and gastric electrical stimulation are not recommended.