New AGA Guideline Adds New Therapies for Managing Moderate-to-Severe UC

The American Gastroenterological Association (AGA) recently published an updated clinical practice guideline for the management of moderate-to-severe ulcerative colitis (UC) in adult outpatients. The update amends the 2020 version, adding new treatments that were FDA-approved after the last guideline was published. Unlike the previous document, the new guideline was developed as a document that will be relatively easy to update as new evidence and treatments become available.

As in the previous guideline, the 2024 AGA guideline panel suggests initiating advanced therapies in patients with moderate-to-severe UC over gradual step-up therapy with 5-aminosalicylates. The list of strongly recommended first-line advanced therapies is expanded to include 10 treatments.

Newcomers to the list include the Janus kinase inhibitor Rinvoq (upadacitinib); the interleukin-23 inhibitors Skyrizi (risankizumab) and Tremfya (guselkumab); and the sphingosine 1-phosphate receptor modulators Velsipity (etrasimod) and Zeposia (ozanimod). Other strongly recommended treatments include Remicade (infliximab) and its biosimilar versions, Simponi (golimumab), Entyvio (vedolizumab), Xeljanz (tofacitinib), and Stelara (ustekinumab) and its biosimilars.

The tumor necrosis factor (TNF) blocker Humira (adalimumab) and its biosimilars fell from strongly recommended to conditionally recommended over no treatment. Filgotinib and Omvoh (mirikizumab) are also conditionally recommended over no treatment. Filgotinib is available in the European Union, the United Kingdom and Japan under the brand name Jyseleca but hasn’t been approved by the FDA for sale in the United States.

When comparing the 10 strongly recommended treatments, Rinvoq emerged as the only intervention with a clinically meaningful difference from placebo of over 20%. The other strongly recommended agents reached the 10% threshold set by the guideline panel. The three treatments that were conditionally recommended did not meet this threshold.

Higher-efficacy medications strongly recommended for advanced therapy-naïve patients include infliximab (brand and biosimilars), Entyvio, Zeposia, Velsipity, Rinvoq, Skyrizi, and Tremfya. For patients with prior exposure to advanced therapies, especially TNF blockers, the three recommended higher-efficacy treatments are Xeljanz, Rinvoq, and ustekinumab (brand and biosimilars).

The AGA has billed the updated guideline is a “living document,” which it plans to review and update every six months based on newly emerging evidence and results from phase 3 and phase 4 trials.