AGA Releases Updated Clinical Crohn’s Disease Guideline Reflecting New Therapies

The American Gastroenterological Association (AGA) has released a living clinical practice guideline on the pharmacologic management of moderate-to-severely active Crohn’s disease (CD), intended to support a comprehensive, patient-centered, evidence-based approach to managing this patient population.

The document was published in Gastroenterology on November 20, 2025, and includes 16 recommendations emphasizing early use of high-efficacy therapies including infliximab, adalimumab, ustekinumab, risankizumab, mirikizumab, guselkumab, and upadacitinib over step-up treatment to improve patient outcomes.

“The science in Crohn’s disease is moving quickly, and our goal was to translate that evidence into clear, meaningful recommendations for front-line clinicians,” guideline author Siddharth Singh, MD, MS, a gastroenterologist and professor of medicine at Mayo Clinic College of Medicine, said in a statement. “It’s patient-centered but also provider-centric. We want to help physicians and advanced practice providers make timely, actionable decisions for their patients.”

Since the publication of the previous AGA guidelines for moderate-to-severely active CD in 2021, 2 additional classes of advanced therapies with 5 novel agents have been approved for this indication, followed by the introduction of biosimilars for several agents over the past decade, including for infliximab, adalimumab, and ustekinumab, as well as subcutaneous delivery options for infliximab and vedolizumab.

In developing the updated guideline, a multidisciplinary panel of clinical experts and methodologists used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to prioritize clinical questions, identify patient-centered outcomes, conduct an evidence synthesis, and develop recommendations. The goal was to provide comprehensive recommendations for the pharmacologic management of moderate-to-severely active CD in adults, as well as recommendations in those without and those with prior exposure to an advanced therapy, the timing of using these therapies, their withdrawal, and appropriate goals of medical management.

In total, the guideline panel agreed on 16 recommendations, of which 1 is a strong recommendation, 9 are conditional recommendations, and 6 were identified as knowledge gaps. In adult patients with moderate-to-severely active CD, the AGA recommends the use of infliximab, adalimumab, ustekinumab, risankizumab, mirikizumab, guselkumab, or upadacitinib over no treatment, and suggests the use of certolizumab pegol or vedolizumab over no treatment.

In individuals who are naïve to advanced therapies, the AGA suggests using a higher efficacy medication like infliximab, adalimumab, vedolizumab, ustekinumab, risankizumab, mirikizumab, or guselkumab rather than a lower-efficacy medication like certolizumab pegol or upadacitinib. In individuals who have previously been exposed to ≥ 1 advanced therapies, the document suggests using a higher efficacy medication like adalimumab, risankizumab, guselkumab, or upadacitinib or intermediate efficacy medication such as ustekinumab or mirikizumab rather than a lower efficacy medication like vedolizumab or certolizumab pegol.

In adult outpatients with moderate-to-severely active CD, the AGA advises against using thiopurine monotherapy for induction of remission, but suggests using thiopurine monotherapy over no treatment for maintenance of (typically corticosteroid-induced) remission. The AGA additionally suggests using subcutaneous methotrexate for induction and maintenance of remission, but recommends against using oral methotrexate.

The guideline further suggests using combination therapy with infliximab and thiopurines over infliximab monotherapy, particularly in those naïve to thiopurines. The AGA also suggests using initial advanced therapy over step therapy involving corticosteroids and/or immunomodulators in patients with moderate-to-severely active CD.

In addition to proposing key implementation considerations for optimal use of these medications, the panel also identified several knowledge gaps and areas for future research, such as how best to assess and target structural healing in CD, including variation in endoscopic and histologic scoring, uncertainty about the clinical relevance of histologic and transmural healing, and a lack of standardized outcome definitions. The optimal timing and frequency of structural assessments and which factors predict early versus delayed healing also remain unclear. Additionally, there is limited evidence on how treatment strategies should be modified to achieve these deeper healing targets, including the safety, long-term outcomes, patient preferences, and cost-effectiveness of dose changes, mechanism switching, or combination advanced therapies.

“These recommendations are about helping patients and providers make informed choices,” Singh said. “Our goal is to empower shared decision-making and ensure these evidence-based options are accessible and covered by insurance.”

References

1. AGA Living Clinical Practice Guideline on the Pharmacologic Management of Moderate-to-Severe Crohn's Disease, Gastroenterology. doi:https://doi.org/10.1053/j.gastro.2025.09.038

2. American Gastroenterological Association. American Gastroenterological Association streamlines Crohn’s disease treatment guidance as new therapies expand options. EurekAlert! November 20, 2025. Accessed November 20, 2025. https://www.eurekalert.org/news-releases/1106367