Oral Icotrokinra Sustains UC Response Through 76 Weeks in ANTHEM-UC LTE

Once-daily oral icotrokinra maintained clinical efficacy with no new safety signals for approximately 1.5 years in adults with moderately to severely active ulcerative colitis (UC), according to data from the ANTHEM-UC long-term extension (LTE) presented at the American College of Gastroenterology (ACG) 2026 Annual Scientific Meeting in Nashville, Tennessee.¹

Results showed most of the 136 icotrokinra-treated participants entering the extension achieved clinical response, clinical remission, and endoscopic improvement at week 76, and 87% remained on treatment through week 78.¹

Icotrokinra is a first-in-class targeted oral peptide which binds the interleukin (IL)-23 receptor, blocking IL-23 signaling at the receptor rather than at the cytokine.¹ It received US Food and Drug Administration approval as Icotyde in March 2026 for moderate to severe plaque psoriasis.³ Maria Abreu, MD, Cedars Sinai, presented the LTE results at ACG.

How Was the ANTHEM-UC Long-Term Extension Designed?

In the phase 2b, randomized, double-blind ANTHEM-UC trial, adults with a modified Mayo score of 5 to 9 and a Mayo endoscopic subscore ≥ 2 received icotrokinra 100 mg, 200 mg, or 400 mg once daily or placebo (1:1:1:1). Randomization was stratified by prior inadequate response or intolerance to advanced therapy and by Mayo endoscopic subscore. All 3 doses met the week 12 primary end point of clinical response, with durable efficacy through week 28.^1,2

Participants with an inadequate response at week 16 underwent a blinded treatment adjustment, with placebo recipients switched to icotrokinra 400 mg and icotrokinra recipients receiving a sham adjustment. Those in clinical response at week 28 could continue study treatment in the LTE, where adjustments to 5-aminosalicylates, corticosteroids, and immunomodulators were permitted. Placebo recipients were discontinued after unblinding.¹

Clinical response, clinical remission, and endoscopic improvement were evaluated at week 76, and symptomatic remission was assessed at each visit. Nonresponder imputation was applied without statistical testing, and the final safety visit occurred at week 78.¹

How Durable Was Icotrokinra Efficacy Through Week 76?

Among the 136 LTE participants, the majority achieved clinical response, clinical remission, and endoscopic improvement at week 76. Of participants in clinical remission at week 76, 97% were also corticosteroid free. Symptomatic remission, observed as early as week 4, was maintained or improved through week 76.¹

Abreu pointed to the 87% treatment retention rate as a key finding of the extension.¹

“In reality, people vote with their feet, right?” said Abreu in an interview with HCPLive. “If they’re not doing well, they’re going to move on and go on to something else.”

Abreu noted the 400-mg group enrolled participants with more extensive disease and greater prior exposure to multiple therapies, an imbalance arising by chance in the phase 2 study.

What Did Long-Term Safety Data Show for Icotrokinra in UC?

Icotrokinra was well tolerated, and no new safety signals were identified. Through week 78 in the full analysis set, exposure-adjusted rates of adverse events (AEs), serious AEs, AEs leading to discontinuation, and infections per 100 patient-years were similar to or lower than placebo. No deaths occurred, and one AE of interest, ductal carcinoma in situ, was reported in the 100-mg group during the LTE.¹

Abreu said she expects the oral IL-23 receptor blocker to be used early in the UC treatment course, after mesalamine or corticosteroids, drawing on clinicians’ experience with injectable IL-23 inhibitors.

“Before they get to a subQ or an IV infusion, I think this is going to be very, very legit,” said Abreu. “It’s very effective. It’s very safe.”

Editors’ Note: Relevant disclosures for Abreu include AbbVie, Alimentiv, Bristol Myers Squibb, Genentech, Johnson & Johnson, Lilly, Pfizer, and others.

References:

1. Abreu MT, et al. Long-term efficacy and safety of icotrokinra, a first-in-class targeted oral peptide that precisely blocks the IL-23 receptor, in ulcerative colitis: results from the ANTHEM-UC long-term extension. Presented at: American College of Gastroenterology 2026 Annual Scientific Meeting; October 9-14, 2026; Nashville, TN.

2. Johnson & Johnson. Icotrokinra meets primary endpoint of clinical response in ulcerative colitis study and shows potential to transform the treatment paradigm for patients. Accessed October 13, 2026. https://www.jnj.com/media-center/press-releases/icotrokinra-meets-primary-endpoint-of-clinical-response-in-ulcerative-colitis-study-and-shows-potential-to-transform-the-treatment-paradigm-for-patients

3. Campbell P. Icotrokinra, an Oral Il-23 Inhibitor, Receives FDA Approval for Psoriasis. HCPLive. Published March 18, 2026. Accessed October 13, 2026. https://www.hcplive.com/view/icotrokinra-receives-fda-approval-for-psoriasis