Vipul Jairath, MBChB, DPhil, MRCP, a professor of medicine, epidemiology, and biostatistics at Western University

Vipul Jaraith, MBChB, DPhil

RELIEVE UCCD: Duvakitug’s Efficacy and Favorable Safety in Crohn’s Disease, With Jairath, MBChB, DPhil

New results from the phase 2b RELIEVE UCCD basket trial reported on the efficacy, safety, and tolerability of

Teva Pharmaceuticals and Sanofi’s investigational monoclonal antibody duvakitug in adults with moderately to severely active 

 and Crohn’s Disease (CD) compared to placebo.

American College of Gastroenterology (ACG)’s 2025 Annual Scientific Meeting

 by Vipul Jairath, MBChB, DPhil, a professor of medicine, epidemiology, and biostatistics at Western University, demonstrated a statistically significant and clinically meaningful endoscopic response with no emergent safety signals in the patient population.

Duvakitug, a human IgG1-λ2 monoclonal antibody targeting TL1A (tumor necrosis factor superfamily member 15), is designed to modulate inflammation and fibrosis associated with the pathogenesis of 

. The phase 2b RELIEVE UCCD study was a randomized, placebo-controlled, double-blind induction trial that evaluated duvakitug in UC and CD under a common basket protocol. The study met its primary endpoints of clinical remission in UC and ≥50% reduction from baseline in the Simple Endoscopic Score for Crohn’s Disease (SES-CD) in CD, as reported in 

“Again, you see a proof of mechanism suggesting that this class of drugs is beneficial in both UC and CD in the phase 2 program, and these have now moved forward into pivotal trials,” said Jairath in an interview with 

Participants were primarily randomly assigned to receive a 2250 mg subcutaneous loading dose of duvakitug or placebo, followed by a dose of duvakitug 450 mg (n = 46), 900 mg (n = 46), or placebo (n = 46) administered every 2 weeks.

The study enrolled 138 adults with moderately to severely active CD with prior documented inadequate response, loss of response, or intolerance to conventional and/or advanced therapies (ATs). Participants were stratified by prior recorded ATs.

Investigators observed a durable efficacy in both duvakitug doses, 26% of patients receiving 450 mg and 48% receiving 900 mg achieved the primary endpoints, compared with 13% of the placebo group. Endoscopic response rates based on the prespecified Bayesian analysis were 13% (450 mg) and 35% (900 mg) after placebo adjustment.

Safety outcomes were consistent with previous reports. The incidence of adverse events was similar between duvakitug 900 mg (43%) and placebo (48%), though higher in the duvakitug 450 mg group (67%). Adverse events leading to discontinuation occurred in 9% of patients receiving duvakitug 450 mg and 2% of those on duvakitug 900 mg or placebo.

“In the phase 2 trial, no new safety signals have been detected with duvakitug beyond what we expected when treating patients with Crohn's disease or ulcerative colitis,” said Jairath.

Editor’s Note: Jairath reports relevant disclosures with AbbVie, Alimentiv, Arena, and others.

Jairaith, V, Kierkuś, J, Duvall, A, et al. Duvakitug, an anti-TL1a mAb, Demonstrates Efficacy and Favorable Safety as an Induction Treatment in Adults With Moderately to Severely Active Crohn’s Disease: Results From the RELIEVE UCCD Phase 2b Basket Trial. Presented at the American College of Gastroenterology (ACG)’s 2025 Annual Scientific Meeting. Phoenix, Arizona. October 27-29, 2025.

Press release: Duvakitug positive phase 2B results demonstrate best-in-class potential in ulcerative colitis and crohn’s disease. Sanofi. December 17, 2024. Accessed November 13, 2025. 

https://www.sanofi.com/en/media-room/press-releases/2024/2024-12-17-12-30-00-2998154

Videos

Phase 2b RELIEVE UCCD results presented at ACG 2025 show duvakitug’s dose-dependent efficacy and favorable safety in Crohn’s disease.


ANTHEM-UC: Icotrokinra Shows Sustained Efficacy in Moderate-to-Severe Ulcerative Colitis, With Vipul Jairath, MBChB, DPhil, MRCP1

When treated with Johnson and Johnson’s icotrokinra, adults with moderate to severe 

 experienced dose-dependent improvements in clinical and endoscopic outcomes with a durable response, and favorable safety in the phase 2b ANTHEM-UC study’s patient population.

 by Vipul Jairath, MBChB, DPhil, MRCP1, a professor of medicine, epidemiology, and biostatistics at Western University, and reported on the safety and efficacy findings for 3 doses of icotrokinra.

Investigational icotrokinra is a first-in-class targeted oral peptide designed to selectively block IL-23 receptor activation, with the potential to modulate or inhibit the inflammatory response in moderate-to-severe plaque psoriasis, ulcerative colitis, and other IL-23 mediated diseases. The drug is being investigated in the ongoing 

“Icotrokinra has a novel mechanism of action. It’s a pill and it’s a peptide, so it can be taken orally. It’s also highly potent for the IL-23 receptor, and I think that’s the key differentiating factor,” said Jairath in an interview in 

 “It has low oral bioavailability, but very high potency for the IL-23 receptor itself. So it blocks the receptor, the site of action, and its subunits, and in doing so, it blocks the downstream inflammatory cytokines mediated through the IL-23 pathway.”

The results presented at ACG come from a 28-week follow-up of ANTHEM-UC, a phase 2b, randomized, double-blind, placebo-controlled, treat-through, dose-ranging study. In adults with moderate to severe UC, participants were randomly assigned in a 1:1:1:1 ratio to once-daily oral icotrokinra 100 mg, 200 mg, 400 mg, or placebo. At week 16, any patient meeting inadequate response criteria had a treatment adjustment where patients in placebo switched to icotrokinra 400 mg, while icotrokinra patients had a sham adjustment.

Investigators noted a week 12 primary endpoint of clinical response and week 28 exploratory endpoints of clinical response, clinical remission, symptomatic remission, endoscopic improvement, and histologic-endoscopic mucosal improvement (HEMI).

Among the 252 randomized participants, the mean modified Mayo score (mMS) was 6.63, with 31.9% having mMS >7 and 58.7% presenting with a Mayo endoscopy subscore (MES) of 3, indicating moderate to severe disease activity. Nearly half (43.3%) were biologic, JAK inhibitor, or sphingosine-1-phosphate receptor modulator inadequate responders (BIO/JAKi/S1P-IR). Patients were stratified by prior biologic, JAKi, or S1P receptor modulator inadequate response status (BIO/JAKi/S1P-IR; yes or no [Y/N]) and by MES 2 or 3.

By week 16, inadequate response criteria were met by 38.1% of placebo-treated patients (n = 24) compared with 17.2%, 17.7%, and 11.1% of those receiving icotrokinra 100 mg (n = 11), 200 mg (n = 11), and 400 mg (n = 7), respectively.

At week 28, all icotrokinra doses demonstrated clinically meaningful improvements versus placebo in clinical response, clinical and symptomatic remission, endoscopic improvement, and histologic-endoscopic mucosal improvement (HEMI), with response rates increasing from week 12 through week 28.

Per each dose group, adverse events occurred in 61.9%, 65.6%, 66.1%, and 60.3% of patients. Serious adverse events and discontinuations were 11.1%, 0%, 6.5%, and 3.2%. No serious infections, malignancies, hepatic events, venous thromboembolism, major cardiovascular events, or deaths were reported in the patient population treated with icotrokinra.

“I think what you see clearly with that is some incremental benefit with continued treatment and persistence of response, said Jairath. “There's been no new safety concerns that would be expected from this class of action. I think most importantly, we haven't seen any areas of specialist interest. No cardiovascular events, no thrombosis, no tuberculosis.”

Jairaith, V, Siegmund, B, Surace, L, et al. Efficacy and Safety of Icotrokinra, a Targeted Oral Peptide That Selectively Blocks IL-23 Receptor Activation, in Ulcerative Colitis: Results From Week 28 of ANTHEM-UC, a Phase 2b Dose-Ranging Trial Presented at the American College of Gastroenterology (ACG)’s 2025 Annual Scientific Meeting. Phoenix, Arizona. October 27-29, 2025.

Icotrokinra long-term results affirm promise of targeted oral peptide with high rates of durable skin clearance and favorable safety profile in difficult-to-treat scalp and genital psoriasis. Jnj.com. Published 2023. Accessed November 12, 2025. 

https://www.investor.jnj.com/investor-news/news-details/2025/Icotrokinra-long-term-results-affirm-promise-of-targeted-oral-peptide-with-high-rates-of-durable-skin-clearance-and-favorable-safety-profile-in-difficult-to-treat-scalp-and-genital-psoriasis/default.aspx

ANTHEM-UC study findings presented at ACG show efficacy, durability and safety of icotrokinra in adults with moderate-to-severe ulcerative colitis.

Vipul Jaraith, MBChB, DPhil

Articles