— Most patients in clinical response or remission with IL-23 inhibitor icotrokinra at 76 weeks
October 14, 2026 • 4 min read
An oral peptide that blocks the interleukin-23 receptor demonstrated durable long-term efficacy in patients with moderately to severely active ulcerative colitis, according to results from the phase IIb ANTHEM-UC trial.
During the long-term extension phase of the study, the majority of patients who remained on treatment with icotrokinra (Icotyde) were in clinical response, clinical remission, or endoscopic improvement at week 76, "all of the things we expect from a drug that works," said Maria Abreu, MD, of Cedars-Sinai Medical Center in Los Angeles, at the American College of Gastroenterologyopens in a new tab or window annual meeting in Nashville, Tennessee.
Patients receiving 100-mg, 200-mg, or 400-mg doses of icotrokinra had clinical response rates of 81.3%, 72.7%, and 72.7%, respectively; clinical remission rates of 56.3%, 59.1%, and 56.8%, with 97% corticosteroid-free; and endoscopic improvement rates of 64.6%, 68.2%, and 63.6%.
The original 12-week phase of the study, the results of which were published in the New England Journal of Medicineopens in a new tab or window, showed that patients assigned to receive 100-mg, 200-mg, or 400-mg doses of the drug achieved clinical response rates of 55%, 58%, and 63%, respectively, compared with a rate of 27% in the placebo group (P<0.001 for all comparisons), meeting the study's primary endpoint.
In addition, a significantly greater proportion of patients receiving 400-mg icotrokinra achieved clinical remission, symptomatic remission, and endoscopic improvement at week 12 compared with placebo patients.
"Unsurprisingly, people who were naive for advanced therapies had higher response rates than those previously exposed," Abreu said. However, even patients previously exposed to advanced therapies had clinical remission rates over 50%, she pointed out.
Moreover, symptomatic remission was observed as early as week 4, with rates that were maintained or improved through week 76.
"So, it looks like over time that there is no fall-off," Abreu told MedPage Today. "People didn't lose the response. The ones that responded continue to do well. And that's another big issue in our field ... that patients do fine at the beginning of treatment, they lose response, and then it's all downhill from there."
"What's nice is that it is an oral drug, and we know it's safe," she added. "So, this could be a really nice advance for our patients."
Considering its safety, and the fact that it is an oral drug that generates early and durable responses, she suggested that icotrokinra will have a role as a first-line advanced therapy if approved for patients with ulcerative colitis.
Earlier this year, the FDA approved icotrokinraopens in a new tab or window for adults and children ages 12 years and older with moderate or severe plaque psoriasis.
According to Abreu and co-authors, the mechanism of receptor blockade with this first-in-class drug contrasts with that of parenterally administered biologic agents that target circulating cytokines, including the p19 subunit of interleukin-23, such as risankizumab (Skyrizi), mirikizumab (Omvoh), and guselkumab (Tremfya), and the p40 subunit of interleukin-12 and interleukin-23, such as ustekinumab (Stelara).
ANTHEM-UCopens in a new tab or window included adults with a diagnosis of ulcerative colitis at least 12 weeks before screening. Patients had to have moderately to severely active disease, defined as a modified Mayo score of at least 5 at baseline and a Mayo endoscopic subscore of at least 2 obtained during central review of the video endoscopy performed at screening.
In addition, participants had to have a history of glucocorticoid dependence; unacceptable side effects with or an inadequate response to oral glucocorticoids, azathioprine, or mercaptopurine; or a history of unacceptable side effects with or an inadequate response to at least one approved advanced therapy for ulcerative colitis at an approved dose.
A total of 252 participants at 115 sites underwent randomization, with 63 assigned to the 400-mg group, 62 to the 200-mg group, 64 to the 100-mg group, and 63 to the placebo group. Patients achieving a clinical response at week 28 were able to continue study treatment in the long-term extension phase.
Across the icotrokinra groups in the long-term extension phase, mean age was 40-46, 55-63% were men, and 66-71% were white.
Groups in the long-term extension phase were well matched, with the exception that more patients in the 400-mg cohort had extensive disease and were more likely to have received two or more classes of therapy in advance of the study.
A majority of participants (85%) stayed in the long-term extension study over 76 weeks.
Adverse events (AEs) were more frequent in the icotrokinra groups than the placebo group, including worsening of ulcerative colitis, upper respiratory tract infection, nasopharyngitis, headache, and arthralgia. However, the proportions of participants with one or more serious AEs or with an AE that led to discontinuation of the trial regimen were not higher in the icotrokinra groups versus the placebo group.
The phase III ICONIC-UC trialopens in a new tab or window is evaluating icotrokinra in adults and adolescents with moderately to severely active ulcerative colitis.