Subcutaneous Guselkumab Meets Week 12 Endpoint In Ulcerative Colitis

Key Takeaways

• Subcutaneous guselkumab induction was associated with higher week 12 clinical remission than placebo.
• Week 24 clinical remission remained higher in both guselkumab groups than in the placebo group.
• Adverse events were reported at similar overall frequencies across groups, with no treatment-related deaths and no new safety concerns.

In the ASTRO phase 3 abstract, adults with moderately to severely active ulcerative colitis receiving subcutaneous guselkumab induction had a 21 percentage point adjusted advantage over placebo in week 12 clinical remission. ASTRO was a double-blind, treat-through, randomized, placebo-controlled phase 3 trial evaluating subcutaneous induction and maintenance treatment. Week 24 remission was also higher in both guselkumab groups, while the overall safety profile was broadly similar across groups.

ASTRO enrolled 418 adults aged 18 years or older at 153 sites in 25 countries after screening 651 participants. Patients were randomized 1:1:1 to guselkumab 400/100 mg, guselkumab 400/200 mg, or matched placebo. Eligibility included a modified Mayo score of 5 to 9, a Mayo endoscopic subscore of at least 2, and a rectal bleeding subscore of at least 1, with inadequate response, intolerance, or corticosteroid dependence. Mean age was 41.7 years, 61% were male, mean disease duration was 7.6 years, and the prespecified primary endpoint was clinical remission at week 12.

At week 12, clinical remission occurred in 77 of 279 guselkumab-treated participants and 9 of 139 placebo-treated participants. Those rates were 28% with guselkumab and 6% with placebo, for an adjusted treatment difference of 21 percentage points. The 95% confidence interval was 14 to 28, and the p value was less than 0.0001.

At week 24, clinical remission occurred in 49 patients (35%) in the guselkumab 400/100 mg group, 51 (36%) in the 400/200 mg group, and 13 (9%) in the placebo group. Through week 24 among participants who received at least one dose, adverse events occurred in 74 of 139 (53%), 85 of 140 (61%), and 91 of 139 (65%). Serious adverse events occurred in 5 (4%), 6 (4%), and 17 (12%), and the most frequently reported events were worsening ulcerative colitis, arthralgia, and upper respiratory tract infection. No treatment-related deaths and no new safety concerns were reported, and the overall safety profile was broadly similar to placebo.

The investigators described the fully subcutaneous regimen as safe and efficacious through 24 weeks and as a treatment option for this population. The reported findings remained centered on 24-week efficacy and safety in adults with moderately to severely active ulcerative colitis.