FDA Approves Guselkumab as First IL-23 Inhibitor With Fully Subcutaneous Induction Regimen for Ulcerative Colitis

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The US FDA has approved a subcutaneous (SC) induction regimen of guselkumab (Tremfya; Johnson & Johnson) for adults with moderately to severely active ulcerative colitis (UC), Johnson & Johnson announced September 19, 2025. With this decision, guselkumab becomes the first IL-23 inhibitor to offer both SC and intravenous (IV) induction options for the treatment of UC and Crohn disease (CD).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 press release.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.”

Approval was supported by results from the phase 3 ASTRO trial, which evaluated SC guselkumab in adults with UC who had inadequate response or intolerance to conventional and advanced therapies. Patients received 400 mg every 4 weeks for induction.¹

At week 12, 26% of patients in the guselkumab group achieved clinical remission compared with 7% in the placebo group (P<.001). Endoscopic improvement was observed in 36% of patients on guselkumab vs 12% on placebo (P<.001). Early separation from placebo occurred as early as week 2 and was sustained through week 24.¹

Week 24 data showed continued benefit with SC induction followed by maintenance therapy. Clinical remission rates were 34% for both 100 mg and 200 mg regimens compared with 10% for placebo (P<.001). Endoscopic improvement was reported in 39% and 44% of patients, respectively, vs 12% for placebo (P<.001). Efficacy was consistent with prior results from the QUASAR study that supported approval of intravenous (IV) induction in UC in 2024.¹

The approved SC induction dosing is 400 mg (two 200 mg injections) at weeks 0, 4, and 8, followed by maintenance dosing of 100 mg every 8 weeks or 200 mg every 4 weeks. An IV induction regimen remains an alternative option. No new safety concerns were reported. The safety profile was consistent with prior guselkumab trials in inflammatory bowel disease.¹

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

Johnson & Johnson announced plans to initiate a head-to-head trial comparing guselkumab with risankizumab in Crohn disease.¹

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. Halsey G. Guselkumab (Tremfya) Wins Approval for Crohn Disease, Fourth Indication for Immune-Mediated Diseases. Patient Care. March 21, 2025. Accessed September 22, 2025. https://www.patientcareonline.com/view/guselkumab-tremfya-wins-approval-for-crohn-disease-fourth-indication-for-immune-mediated-diseases