Q4 2025 Recap: Gastroenterology News and Updates

The fourth quarter of 2025 marked a pivotal period in gastroenterology, with major regulatory decisions and updated clinical guidance reflecting the accelerating pace of therapeutic innovation.

New and expanded US Food and Drug Administration (FDA) approvals broadened treatment options across inflammatory bowel disease and functional GI disorders, including the first pediatric indication for linaclotide in IBS-C, an updated indication for upadacitinib in both ulcerative colitis (UC) and Crohn’s disease, and more convenient dosing with a single-injection formulation of mirikizumab for UC maintenance. In parallel, the American Gastroenterological Association (AGA) released an updated, living guideline for moderate to severe Crohn’s disease that emphasizes early use of high-efficacy therapies over traditional step-up approaches.

Beyond approvals and guidelines, late-breaking trial data and expert insights highlighted continued momentum in UC drug development and long-term disease management. 4-year extension data from LUCENT-3 reinforced the durability of IL-23p19 inhibition with mirikizumab, while phase 2 and 3 studies of novel agents such as obefazimod and icotrokinra pointed to emerging non-immunosuppressive and next-generation options for patients with persistent unmet needs. Rounding out the quarter, an American College of Physicians (ACP) position paper on colorectal cancer screening and surveillance underscored ongoing efforts to refine quality measures and align policy with evidence-based care.

Check out this recap of what made headlines in Q4 of 2025:

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

On November 20, 2025, the AGA released a living clinical practice guideline on the pharmacologic management of moderate-to-severely active Crohn’s disease, intended to support a comprehensive, patient-centered, evidence-based approach to managing this patient population. The document 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.

FDA Approves Linaclotide (Linzess) Capsules for Pediatric IBS-C

On November 5, 2025, the FDA approved linaclotide (Linzess) capsules for pediatric patients ≥ 7 years of age with IBS-C, making it the first treatment approved for IBS-C in this patient population. The approval was supported by extrapolation of efficacy from adequate and well-controlled studies in adults and a 12-week double-blind, randomized, parallel-group trial in pediatric patients 7-17 years of age who met modified Rome III criteria for child/adolescent IBS-C.

ACP Releases Position Paper on Colorectal Cancer Screening, Surveillance

On October 21, 2025, the ACP released a position paper reviewing current performance measures for colorectal cancer screening and surveillance, ultimately supporting 1 of 5 reviewed measures. Published in Annals of Internal Medicine, the paper seeks to inform physicians, payers, and policymakers in their selection and use of performance measures and make recommendations for measures that could be developed.

FDA Approves Updated Indication for Upadacitinib (Rinvoq) in IBD

On October 13, 2025, the FDA approved a supplemental new drug application (sNDA) updating the indication statement for upadacitinib (Rinvoq) for the treatment of adults with moderately to severely active UC and moderately to severely active CD, now allowing for use of upadacitinib after patients have received ≥ 1 approved systemic therapy in the event tumor necrosis factor (TNF) blockers are clinically inadvisable. Previously, upadacitinib was only indicated for adults who had an inadequate response or intolerance to ≥ 1 blockers.

FDA Approves Single-Dose Formulation of Mirikizumab-mrkz for Ulcerative Colitis

On October 27, 2025, the FDA approved a single-injection, once-monthly maintenance regimen of mirikizumab-mrkz (Omvoh) 200 mg/2 mL for subcutaneous use in adults with moderately to severely active UC. The decision was based on results from a phase 1 study comparing a single 200 mg/2 mL subcutaneous injection to 2 100 mg/1 mL injections in participants, ultimately confirming mirikizumab single-injection is bioequivalent to the previously approved 2-injection regimen.

LUCENT-3: Mirikizumab (Omvoh) Shows Sustained Benefit in Ulcerative Colitis Through 4 Years

On October 7, 2025, Eli Lilly and Company announced data from the phase 3 LUCENT-3 open-label extension study establishing mirikizumab-mrkz (Omvoh) as the first and only interleukin-23p19 (IL-23p19) to help patients with moderately to severely active UC achieve sustained, long-term outcomes through 4 years. Results were seen across multiple symptomatic, clinical, endoscopic, histologic and quality-of-life measures, including among patients who had previously failed a biologic or advanced therapy (27%).

Obefazimod As An “Exciting” Potential Treatment for Ulcerative Colitis, With Bruce Sands, MD

Despite an expanding treatment landscape, UC remains a challenging chronic condition for many patients, particularly those with moderate to severe disease who fail multiple lines of therapy. The need for new, effective, and better-tolerated options continues to drive innovation in the field.

At the American College of Gastroenterology (ACG)’s 2025 Annual Scientific Meeting, attention turned to obefazimod, a first-in-class small molecule with a novel, non-immunosuppressive mechanism of action. In this interview, Bruce Sands, MD, Chief of the Dr. Henry D. Janowitz Division of Gastroenterology at the Mount Sinai Medical Center and the Dr. Burrill B. Crohn Professor of Medicine at the Icahn School of Medicine at Mount Sinai, reviewed data from a pair of phase 3 studies, ABTECT 1 and ABTECT 2, presented during a late-breaking session at ACG.

ANTHEM-UC: Icotrokinra Shows Sustained Efficacy in Moderate-to-Severe Ulcerative Colitis, With Vipul Jairath, MBChB, DPhil

When treated with Johnson and Johnson’s icotrokinra, adults with moderate to severe UC experienced dose-dependent improvements in clinical and endoscopic outcomes with a durable response, and favorable safety in the phase 2b ANTHEM-UC study’s patient population. Vipul Jairath, MBChB, DPhil, breaks down some of these findings and their significance in this interview at the ACG 2025 Annual Scientific Meeting.