Subcutaneous Guselkumab Induction Achieves Clinical Remission in Moderate to Severe Ulcerative Colitis
A fully subcutaneous induction and maintenance regimen of guselkumab demonstrated significant efficacy and a favorable safety profile in adults with moderately to severely active ulcerative colitis (UC), according to results from the phase 3 ASTRO trial.
The double-blind, randomized, placebo-controlled ASTRO trial enrolled adults with active UC across 153 sites in 25 countries. Participants had a modified Mayo score of 5 to 9, endoscopic disease activity, and prior inadequate response, intolerance, or dependence on corticosteroids, immunomodulators, biologics, Janus kinase inhibitors, or sphingosine 1-phosphate receptor modulators. Patients were randomized to one of two subcutaneous guselkumab induction regimens—400 mg at weeks 0, 4, and 8 followed by either 100 mg every 8 weeks or 200 mg every 4 weeks—or placebo.
At week 12, the primary endpoint was met. A significantly greater proportion of patients receiving guselkumab induction achieved clinical remission compared with placebo (28% vs 6%), representing an adjusted treatment difference of 21 percentage points (p<0.0001). At week 24, remission rates remained significantly higher in both guselkumab maintenance groups (35% and 36%) compared with placebo (9%).
The investigators concluded that “subcutaneous guselkumab induction and maintenance was safe and efficacious for 24 weeks in participants with moderately to severely active ulcerative colitis.” Importantly, they noted that these results “establish a fully subcutaneous guselkumab regimen as a treatment option in this patient population.”
Safety outcomes were reassuring. Adverse event rates in both guselkumab groups were comparable to placebo, and serious adverse events occurred less frequently in guselkumab-treated patients. There were no treatment-related deaths and no new safety signals identified. Worsening UC was more common in the placebo group than in either guselkumab group.
For gastroenterologists, the key takeaway is that guselkumab can be effectively initiated and maintained using a fully subcutaneous regimen in moderate to severe UC. This approach may reduce infusion-related barriers, expand patient access, and simplify treatment logistics while maintaining robust clinical efficacy and safety.
Reference
Long M, Allegretti JR, Danese S, et al. Efficacy and safety of subcutaneous guselkumab induction therapy in participants with moderately to severely active ulcerative colitis (ASTRO): a double-blind, treat-through, randomised, placebo-controlled, phase 3 trial. The Lancet Gastroenterology & Hepatology. Published online January 2026. doi: 10.1016/S2468-1253(25)00322-X
