Subcutaneous administration of the anti–interleukin-23 agent guselkumab during 12 weeks of induction resulted in achievement of all study end points in people with moderate to severely active ulcerative colitis in the phase 3 ASTRO trial, reported investigators at the 2025 European Crohn’s and Colitis Organisation Congress.
The earlier QUASAR study found similar benefits for IV induction of guselkumab (Tremfya, Johnson & Johnson) to treat UC (Lancet 2025;405[10472]:33-49), which led to FDA approval of the IV form for that indication in 2024. The QUASAR data also showed the benefit of subcutaneous maintenance therapy with guselkumab.
“The week 12 results from the ASTRO study build on data from the QUASAR study,” said investigator Laurent Peyrin-Biroulet, MD, PhD, the director of the inflammatory bowel disease unit at Nancy University Hospital, in France. “The flexibility of a fully subcutaneous treatment regimen would be a welcome option for many patients, especially those with busy and active lifestyles.”
In ASTRO, 279 adults with moderate to severely active UC—defined as a baseline modified Mayo score from 5 to 9, including a rectal bleeding subscore of at least 1 and an endoscopic subscore of at least 2—received 400 mg of subcutaneous guselkumab at weeks 0, 4 and 8 over a total of 12 weeks. All participants were either intolerant of or unresponsive to conventional UC therapies, such as corticosteroids, biologics, ozanimod and Janus kinase inhibitors.
The primary end point was clinical remission, defined as a Mayo stool frequency subscore of 0 or 1 that had not increased at baseline, a Mayo rectal bleeding subscore of 0, and a Mayo endoscopic subscore of 0 or 1 with no friability present on endoscopy. Clinical response was a decrease in the modified Mayo score by at least 30% and at least 2 points, with either a =1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1; endoscopic improvement was defined as an endoscopic subscore of 0 or 1 with no friability.
By week 12, patients who received subcutaneous guselkumab had significantly higher levels of clinical remission (27.6% subcutaneous vs. 6.5% placebo; difference, 21.1%; 95% CI, 14.5%-27.6%; P<0.001), clinical response (65.6% vs. 34.5%; difference, 31%; 21.6%-40.5%; P<0.001) and endoscopic improvement (37.3% vs. 12.9%; difference 24.3%, 95% CI, 16.6%-31.9%; P<0.001) than the 139 participants who took placebo.
Overall, 30.5% of people in the subcutaneous induction arm achieved histo-endoscopic mucosal improvement, versus 10.8% in the placebo arm (difference, 19.6%; 95% CI, 12.4%-26.9%). Histo-endoscopic mucosal improvement was defined as endoscopic improvement, no tissue erosion, neutrophil penetration into less than 5% of crypts, no crypt destruction, and no erosions, ulcerations or granulation tissue per the Geboes grading system.
No IV ‘Kick Start’ Needed
“We’ve often felt that an IV induction is needed in ulcerative colitis due to a large inflammatory burden and that somehow IV was needed to ‘kick-start’ induction. The fact that the subcutaneous form had consistent efficacy with IV is impressive. Also, there were no new safety signals with the subcutaneous form,” Miguel Regueiro, MD, a professor of medicine and the chief of the Digestive Disease Institute at Cleveland Clinic, in Ohio, told Gastroenterology & Endoscopy News.
Dr. Regueiro noted that this is the first IL-23 inhibitor with a subcutaneous induction method for treating UC.
“I think that this could be an ‘easier’ way to administer an IL-23 inhibitor, that is, a patient starts on subcutaneous guselkumab for induction and continues subcutaneous guselkumab in maintenance,” Dr. Regueiro added. “There is no need to start IV and then switch to subcutaneous.”
A maintenance trial within ASTRO is ongoing, according to Esi Lamousé-Smith, MD, PhD, the vice president and Gastroenterology Disease Area Leader, Immunology, at Johnson & Johnson in Spring House, Pa.
Dr. Lamousé-Smith noted that the phase 3 GRAVITI trials showed similar benefits of subcutaneous guselkumab for Crohn’s disease, in induction and maintenance (Gastroenterology 2025:S0016-5085[25]00522-0), and FDA approval for Crohn’s disease is under review.
—Marcus A. Banks
Dr. Lamousé-Smith is an employee of Johnson & Johnson. Drs. Peyrin-Biroulet and Regueiro reported a financial relationship with Johnson & Johnson.
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