Guselkumab Subcutaneous Induction Advances Ulcerative Colitis Care, With David Rubin, MD

The treatment landscape for ulcerative colitis (UC) took an important step forward with the US Food and Drug Administration’s approval of a subcutaneous (SC) induction regimen for guselkumab (Tremfya).

The September 19, 2025, decision makes guselkumab the first and only IL-23 inhibitor to offer both intravenous (IV) and SC induction options in inflammatory bowel disease (IBD) and was 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.

“Having subcutaneous induction of guselkumab for ulcerative colitis has two important implications. The first one is for patients, and the sense of making this a bit more convenient for them to be able to either have it done in the doctor's office in a short period of time, or learning how to do it and doing it themselves, which most of our patients do,” David Rubin, MD, a professor of medicine and director of the IBD Center at the University of Chicago and chair of the International Organization for the Study of IBD, explained to HCPLive. “The second one that I think is important, that we should really understand, is the simplification of preauthorization for the drug from insurance companies.”

In ASTRO, 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. 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.

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.

“The data in ASTRO are interesting and important, because the subcutaneous loading in ASTRO at week 12 looks just like the IV loading from QUASAR at week 12,” Rubin explained. “In other words, as much as people may have thought that a subcutaneous loading phase might be a weaker delivery or a lower dose or some other adjustment that's not going to be as effective as what was seen with IV, it actually looks the same. In fact, arguably, some of the numbers even look better.”

Looking at data for guselkumab from various studies in IV and SC across both Crohn’s disease and UC, Rubin also points to the importance of remission at week 12, which he says has consistently predicted more success in maintenance. He additionally highlights guselkumab’s consistent benefit across various subgroups for both SC and IV induction in UC as well as its safety and tolerability.

“I've often said that the sign of progress in our field is when we start thinking about convenience,” Rubin said. “In addition to the general mechanism, when you think about convenience as the next thing you're going to talk about to patients and to ourselves and our staff, it really means that we've started to make some progress, because we've gotten past understanding that, yes, this mechanism works, and now we can start talking about how we deliver it in a more tolerable way, or how we get it to the patient with less hassle.”

Editors’ note: Relevant disclosures for Rubin include Takeda, AbbVie, Abivax SA, Bristol Myers Squibb, Celltrion, Eli Lilly, Genentech/Roche, Janssen, Pfizer, Sanofi, Takeda, and others.

Reference

Brooks A. FDA Approves Guselkumab (Tremfya) Subcutaneous Induction Regimen for Ulcerative Colitis. HCPLive. September 19, 2025. Accessed September 26, 2025. https://www.hcplive.com/view/fda-approves-guselkumab-tremfya-subcutaneous-induction-regimen-for-ulcerative-colitis