Guselkumab becomes the first and only IL-23 inhibitor with a fully subcutaneous induction regimen for adults with ulcerative colitis.
The FDA approved a subcutaneous (SC) induction regimen of guselkumab (Tremfya; Johnson & Johnson) for the treatment of adults with moderately to severely active ulcerative colitis (UC), becoming the first and only IL-23 inhibitor to offer both SC and intravenous induction options for UC and Crohn disease, according to a news release from Johnson & Johnson.1
This approval was based on results from the randomized, double-blind, placebo-controlled, parallel-group, multicenter, treat-through ASTRO phase 3 study (NCT05528510), which evaluated the efficacy of 400-mg gulsekumab SC induction therapy in adults with UC who previously had an inadequate response or intolerance to standard of care, prior biologics, or approved Janus kinase inhibitors. In the trial, investigators observed that all multiplicity-controlled primary and secondary endpoints had statistically significant and clinically meaningful improvements across all clinical and endoscopic measures with gulsekumab SC therapy.1,2
“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 T. Rubin, MD, director of the inflammatory bowel disease center at University of Chicago and ASTRO investigator, said in the news release. “With today’s approval, UC patients and providers now have the choice of starting [gulsekumab] 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.”1
According to the ASTRO trial design, patients were randomized 1:1:1 to receive either guselkumab 400 mg SC induction at weeks 0, 4, and 8, followed by gulsekumab 200 mg SC every 4 weeks (Q4W); guselkumab 400 mg SC induction at weeks 0, 4, and 8 followed by gulselkumab 100 mg SC every 8 weeks (Q8W); or placebo. The authors noted that the maintenance dose regimens were the same as those featured in the phase 3 QUASAR program, which previously established the safety and efficacy of intravenous guselkumab induction therapy in UC.1,3
Trial Name: A Study of Guselkumab Therapy in Participants With Moderately to Severely Active Ulcerative Colitis (ASTRO)
ClinicalTrials.gov Identifier: NCT05528510
Sponsor: Janssen Research & Development, LLC
Estimated Completion Date: October 6, 2028
An early symptomatic response was observed with both guselkumab-based regimens, with the treatment distancing itself from placebo as early as 2 weeks and sustaining the response across 24 weeks. There were significantly higher proportions of patients treated with guselkumab 400 mg SC Q4W who achieved clinical remission (26% vs 7%; P < .001) and endoscopic improvement (36% vs 12%; P < .001) at week 12 compared with placebo, according to the investigators.1
In an important sign of efficacy, the efficacy of both SC and intravenous induction was comparable across subgroups—including patients with either severe or refractory disease. Critically, both induction routes elicited a similar time to onset of efficacy.1
At week 24, SC induction followed by SC maintenance also demonstrated meaningful and significant improvements in both 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) compared with patients treated with placebo. The meaningful efficacy demonstrated across 24 weeks and doses indicate the potential for guselkumab to significantly impact UC treatment and relieve patients of the burdens associated with intravenous induction.1
This is not the first approval for guselkumab in its regulatory journey. In 2024, the IL-23 inhibitor received its first approval for moderate-to-severe UC based on positive results from the QUASAR study program. In that trial, 50% of patients receiving 200 mg intravenous maintenance therapy every 4 weeks achieved clinical remission at week 44.3,4
More recently, the FDA approved guselkumab for the treatment of Crohn disease, another gastrointestinal disorder that is a major cause of inflammatory bowel disease. It became the first IL-23 inhibitor offering SC and intravenous induction options specifically for Crohn disease. Results from the GRAVITI trial affirmed the efficacy of SC guselkumab in Crohn disease, with 41.3% of those receiving SC induction achieving an endoscopic response and a robust rate of clinical remission.5
In ASTRO, the investigators demonstrated that the chosen doses achieved results consistent with the FDA-approved 200-mg intravenous induction regimen of guselkumab. Based on these results, the recommended SC induction dosage of guselkumab is 400 mg, given as 2 consecutive injections of 200 mg each, at weeks 0, 4, and 8. For maintenance dosing, the recommended regimen is either 100 mg SC at week 16 and every 8 weeks thereafter, or 200 mg SC injection at week 12 and e very 4 weeks thereafter. Pharmacists should counsel patients that the lowest effective recommended dosage to maintain a therapeutic response should be used.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 disease,” Chris Gasink, MD, vice president of medical affairs, gastroenterology and autoantibody, at Johnson & Johnson Innovative Medicine, said in the news release.1
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September 22nd 2025
September 22nd 2025
