ACG 2026: Oral IL-23 blocker shows promise for ulcerative colitis

Clinical takeaway: For patients with moderate to severe ulcerative colitis, oral icotrokinra may offer a new targeted treatment option without the need for injections or infusions. In a phase 2b trial, the IL-23 receptor blocker improved clinical response, remission, and endoscopic outcomes while maintaining a safety profile similar to placebo.

IL-23 inhibition is an established strategy in inflammatory bowel disease, but currently available agents require intravenous or subcutaneous administration. An effective oral therapy could expand treatment options and potentially improve patient acceptance and adherence.

In the global ANTHEM-UC trial, results of which were presented at the ACG annual meeting and published in the New England Journal of Medicine, 252 adults with moderately to severely active ulcerative colitis were randomized to once-daily oral icotrokinra at doses of 100 mg, 200 mg, or 400 mg, or to placebo. Nearly half had previously received advanced therapies, including biologics, making the population representative of patients often seen in specialty practice.

At 12 weeks, clinical response rates were nearly doubled with icotrokinra. Responses occurred in 63% of patients receiving 400 mg, 58% receiving 200 mg, and 55% receiving 100 mg, compared with 27% receiving placebo. The highest dose also achieved clinical remission in 30% of patients versus 11% with placebo, while symptomatic remission occurred in 46% versus 19%, respectively. Endoscopic improvement was seen in 37% of patients on 400 mg compared with 14% on placebo. Benefits were observed even among patients with prior treatment failures, according to investigators.

Treatment effects persisted through 28 weeks, and adverse-event rates were similar across icotrokinra and placebo groups. Serious adverse events were uncommon and occurred in 2% of patients receiving the highest dose versus 10% of those receiving placebo.

“The fact that the medicine can be taken orally will help us improve the range of options we have for treating patients,” said study author Maria T. Abreu, MD in a press release.

Source: Abreu MT, et al. (2026 Oct 14) N Engl J Med. Phase 2 Trial of Icotrokinra for Patients with Ulcerative Colitis