Colon to Rectum
Gastroenterology. 2023;165(6):1443–57
Guselkumab in patients with moderately to severely active ulcerative colitis: QUASAR phase 2b induction study
Background and aims: The QUASAR phase 2b induction study evaluated the efficacy and safety of guselkumab, an interleukin-23p19 subunit antagonist, in patients with moderately to severely active ulcerative colitis with prior inadequate response and/or intolerance to corticosteroids, immunosuppressants, and/or advanced therapy.
Methods: In this double-blind, placebo-controlled, dose-ranging, induction study, patients were randomized (1:1:1) to receive intravenous guselkumab 200 mg or 400 mg or placebo at weeks 0/4/8. The primary end point was clinical response (compared with baseline, modified Mayo score decrease ≥ 30% and ≥ 2 points, rectal bleeding subscore ≥ 1-point decrease or subscore of 0/1) at week 12. Guselkumab and placebo week-12 clinical non-responders received subcutaneous or intravenous guselkumab 200 mg, respectively, at weeks 12/16/20 (uncontrolled study period).
Results: The primary analysis population included patients with baseline modified Mayo scores ≥ 5 and ≤ 9 (intravenous guselkumab 200 mg, n = 101; 400 mg, n = 107; placebo, n = 105). Week-12 clinical response percentage was greater with guselkumab 200 mg (61.4%) and 400 mg (60.7%) versus placebo (27.6%; both p < 0.001). Greater proportions of guselkumab-treated versus placebo-treated patients achieved all major secondary end points (clinical remission, symptomatic remission, endoscopic improvement, histo-endoscopic mucosal improvement, and endoscopic normalization) at week 12. Among guselkumab week-12 clinical non-responders, 54.3% and 50.0% of patients in the 200- and 400-mg groups, respectively, achieved clinical response at week 24. Safety was similar among guselkumab and placebo groups.
Conclusions: Guselkumab intravenous induction was effective versus placebo in patients with moderately to severely active ulcerative colitis. Guselkumab was safe, and efficacy and safety were similar between guselkumab dose groups.