Maria Abreu, MD, is Executive Director of the F. Widjaja Inflammatory Bowel Disease Institute at Cedars-Sinai.

Maria Abreu, MD

Once-daily oral icotrokinra maintained clinical efficacy with no new safety signals for approximately 1.5 years in adults with moderately to severely active 

, according to data from the ANTHEM-UC long-term extension (LTE) presented at the 

American College of Gastroenterology (ACG) 2026 Annual Scientific Meeting

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.

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.

 It received US Food and Drug Administration approval as Icotyde in March 2026 for moderate to severe plaque psoriasis.

 Maria Abreu, MD, Cedars Sinai, presented the LTE results at ACG.

Oral Icotrokinra for Ulcerative Colitis: 76-Week ANTHEM-UC Data

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.

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.

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.

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.

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

“In reality, people vote with their feet, right?” said Abreu in an interview with 

. “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.

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.

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.

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

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

Videos

Maria Abreu, MD, discusses 76-week ANTHEM-UC extension data showing once-daily oral icotrokinra maintained efficacy with no new safety signals in UC. 

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

Is Dual-Target Therapy the Future of Ulcerative Colitis? New Phase 2b JNJ-4804 Data

For patients with ulcerative colitis (UC) who have failed multiple lines of therapy, treatment options are limited and outcomes are often poor. A novel investigational approach simultaneously targeting 2 distinct inflammatory pathways with a single fixed-dose co-antibody may offer hope for changing that reality.

Phase 2b data from the DUET-UC trial presented at Digestive Disease Week (DDW) 2026 in Chicago, IL, by Maria Abreu, MD, Executive Director of the F. Widjaja Inflammatory Bowel Disease Institute at Cedars-Sinai, position JNJ-78934804 (JNJ-4804) as a potentially transformational therapy for one of the most difficult-to-treat populations in inflammatory bowel disease (IBD).

"Most of the advanced therapies in ulcerative colitis and Crohn's disease target one very specific thing." Abreu told 

. "I tell my patients an anti-TNF can only do one thing, it can only find TNF and block TNF. In the case of an anti IL-23, it could only do this one thing, so we view that these are 2 different aspects of the immune response, and so targeting these 2 orthogonal pathways makes intellectual sense.”

DUET-UC was a phase 2b, randomized, double-blind, dose-ranging study in which 572 patients with moderately to severely active UC were randomized to placebo, guselkumab, golimumab, or JNJ-4804 at low, mid, or high doses. The primary endpoint was clinical remission at Week 48.

Of note, the trial enrolled an unusually refractory population: all patients had inadequate response or intolerance to ≥ 1 systemic therapy class, 45% had failed ≥ 2, and some had cycled through 6 or more prior biologics across multiple mechanisms of action. At baseline, 72% had severe endoscopic disease.

"They enrolled a group of patients that no one wants in their study," Abreu said. "For the most part, studies want people who've never been on any therapy, or maybe they'll let one or two previous therapies. In this study, they said anyone who's been on more than one mechanism of action, not just one drug, but one mechanism of action, is allowed to enroll.”

In the overall population, high-dose JNJ-4804 was significantly superior to golimumab for clinical remission at Week 48 and performed similarly to guselkumab. Abreu noted that the most compelling findings, however, came from the highly refractory subgroup who had failed ≥ 2 systemic therapy classes.

In this population, high-dose JNJ-4804 demonstrated clinically meaningful improvements across all endpoints compared with both monotherapies and placebo, including a 28-point advantage over golimumab and a 12-point advantage over guselkumab in clinical remission rates. Benefits were similarly pronounced for corticosteroid-free remission, endoscopic improvement, and histologic remission with endoscopic improvement.

Abreu highlighted the molecular underpinning of these results, noting that earlier biopsy data from the VEGA study showed that combining anti-IL-23 and anti-TNF therapies produced far greater reductions in inflammatory gene expression and greater increases in epithelial repair pathways than either agent alone.

Safety events per 100 patient-years in the JNJ-4804 groups were comparable to or lower than those observed with the monotherapies. Serious infection rates were low across all arms, and no new safety signals emerged over the 48-week study period.

"There is no increase in adverse events," Abreu said. "And this was a 48-week study — it wasn't like a 12-week study. These people did fine, so I think that there's every reason to believe that in the larger studies, we're not going to unmask yet another side effect of the two together.”

Abreu expressed hope that the results would accelerate phase 3 development and encourage broader collaboration across companies to test additional combination permutations, a shift she described as long overdue for the field.

Editors’ note: Abreu reports relevant disclosures with AbbVie, Bristol Myers Squibb, Eli Lilly and Company, Gilead Sciences, Janssen Pharmaceuticals, Pfizer, and others.

Abreu M, Sands BE, Vermeire S, et al. EFFICACY AND SAFETY OF THE FIRST CO-ANTIBODY THERAPY, JNJ-78934804, IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS REFRACTORY TO SYSTEMIC THERAPIES. Presented at Digestive Disease Week (DDW) 2026; Chicago, IL; May 2–5, 2026.

Johnson & Johnson. Johnson & Johnson investigational co-antibody therapy JNJ-4804 shows potential to raise the bar for clinical efficacy in treating refractory inflammatory bowel disease. PR Newswire. Published May 05, 2026. Accessed May 05, 2026. 

https://www.prnewswire.com/news-releases/johnson--johnson-investigational-co-antibody-therapy-jnj-4804-shows-potential-to-raise-the-bar-for-clinical-efficacy-in-treating-refractory-inflammatory-bowel-disease-302761831.html

Feagan BG, Sands BE, Sandborn WJ, et al. Guselkumab plus golimumab combination therapy versus guselkumab or golimumab monotherapy in patients with ulcerative colitis (VEGA): a randomised, double-blind, controlled, phase 2, proof-of-concept trial. 

. 2023;8(4):307-320. doi:10.1016/S2468-1253(22)00427-7

Maria Abreu, MD, breaks down efficacy and safety data for dual-target co-antibody JNJ-4804, offering a potential new option for heavily pretreated UC patients.

Maria Abreu, MD

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