FDA Approves Guselkumab (Tremfya) Subcutaneous Induction Regimen for Ulcerative Colitis

The US Food and Drug Administration (FDA) has approved a subcutaneous (SC) induction regimen of guselkumab (Tremfya) for the treatment of adults with moderately to severely active ulcerative colitis (UC), making guselkumab the first and only IL-23 inhibitor to offer both SC and intravenous (IV) induction options for the treatment of UC and Crohn’s disease (CD).1

According to a September 19, 2025, press release from Johnson & Johnson, the UC SC induction approval is based on results from the phase 3 ASTRO trial, which employed a treat-through design to evaluate the efficacy and safety of guselkumab SC induction therapy in adults with moderately to severely active UC who had an inadequate response or intolerance to conventional therapy and advanced therapies.1

“Historically, IL-23 inhibitors have required IV infusions at the start of therapy, which can create barriers to starting treatment or be burdensome for some patients and clinicians,” David Rubin, MD, Director, Inflammatory Bowel Disease Center, University of Chicago Medicine and study investigator, said in a statement.1 “With today’s approval, UC patients and providers now have the choice of starting [guselkumab] with a self-administered subcutaneous injection, with the same efficacy and safety that were established with IV induction in the prior clinical trials and subsequently seen in our real-world practice.”

Guselkumab is the first and only approved fully-human, dual-acting monoclonal antibody that blocks IL-23 while also binding to CD64, a receptor on cells that produce IL-23. It received initial approval from the FDA in 2017 for treatment of moderate-to-severe plaque psoriasis, followed by subsequent indications for active psoriatic arthritis and moderately to severely active UC in 2020 and 2024, respectively. In March 2025, it earned its fourth indication when it was approved for CD based on data from the GALAXI trials.1,2

ASTRO was a randomized, double-blind, placebo-controlled, parallel-group, multicenter, treat-through phase 3 study designed to evaluate the efficacy and safety of guselkumab SC induction therapy (400 mg at weeks 0, 4, and 8) in adults with moderately to severely active UC who had an inadequate response or intolerance to conventional therapy, prior biologics, and/or ozanimod or approved JAK inhibitors. In the trial, patients were randomly assigned in a 1:1:1 ratio to receive guselkumab 400 mg SC induction at Weeks 0, 4 and 8 followed by guselkumab 200 mg SC every 4 weeks (q4w); or guselkumab 400 mg SC induction at Weeks 0, 4 and 8, followed by guselkumab 100 mg SC every 8 weeks (q8w); or placebo.1

In the trial, all multiplicity-controlled primary and secondary endpoints demonstrated statistically significant and clinically meaningful improvements with guselkumab compared to placebo across all clinical and endoscopic measures. Among these was early symptomatic response, with guselkumab separating from placebo as early as 2 weeks and sustained through week 24.1

Additionally, significantly greater proportions of patients treated with guselkumab 400 mg SC q4w achieved clinical remission (26% vs 7%; P <.001) and endoscopic improvement (36% vs 12%; P <.001) at week 12 versus those treated with placebo. Of note, results were consistent with the FDA-approved 200mg IV induction regimen, which previously achieved clinical remission (23% vs 8%; P <.001) and endoscopic improvement (27% vs 11%; P <.001) versus those treated with placebo.1

Week 24 SC induction followed by SC maintenance data also demonstrated statistically significant and clinically meaningful improvements in clinical remission (100 mg: 34%, 200 mg: 34% vs 10%; P <.001) and endoscopic improvement (100 mg: 39%, 200 mg: 44% vs 12%; P <.001) versus those treated with placebo.1

Based on the positive outcomes of clinical programs, Johnson & Johnson is initiating the first IL-23 inhibitor head-to-head study seeking to demonstrate the superiority of guselkumab versus risankizumab (Skyrizi).1

“With today’s approval, [guselkumab] is the first and only IL-23 inhibitor to offer inflammatory bowel disease patients robust clinical and endoscopic results with a fully subcutaneous regimen, now across both ulcerative colitis and Crohn’s disease,” said Chris Gasink, MD, Vice President, Medical Affairs, Gastroenterology & Autoantibody, Johnson & Johnson Innovative Medicine.1 “The initiation of a head-to-head study in Crohn’s disease is a further testament to our commitment to advancing the clinical evidence of [guselkumab] in IBD.”

References

1. Johnson & Johnson. TREMFYA® (guselkumab) achieves U.S. approval for subcutaneous induction in adults with ulcerative colitis, now the first and only IL-23 inhibitor with a fully subcutaneous regimen. September 19, 2025. Accessed September 19, 2025. https://www.jnj.com/media-center/press-releases/tremfya-guselkumab-achieves-u-s-approval-for-subcutaneous-induction-in-adults-with-ulcerative-colitis-now-the-first-and-only-il-23-inhibitor-with-a-fully-subcutaneous-regimen

2. Campbell P. FDA Approves Guselkumab (Tremfya) For Crohn Disease. HCPLive. March 20, 2025. Accessed September 19, 2025. https://www.hcplive.com/view/fda-approves-guselkumab-tremfya-for-crohn-disease