BACKGROUND & 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 (UC) 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 or 400 mg or placebo at weeks 0/4/8. The primary endpoint 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 nonresponders 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%) vs placebo (27.6%; both P < .001). Greater proportions of guselkumab-treated vs placebo-treated patients achieved all major secondary endpoints (clinical remission, symptomatic remission, endoscopic improvement, histo-endoscopic mucosal improvement, and endoscopic normalization) at week 12. Among guselkumab week-12 clinical nonresponders, 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 vs placebo in patients with moderately to severely active UC. Guselkumab was safe, and efficacy and safety were similar between guselkumab dose groups. CLINICALTRIALS: gov number: NCT04033445.

Department of Gastroenterology Nancy University Hospital F 54500 Vandœuvre lès Nancy France; INSERM NGERE University of Lorraine F 54000 Nancy France; INFINY Institute Nancy University Hospital F 54500 Vandœuvre lès Nancy France; FHU CURE Nancy University Hospital F 54500 Vandœuvre lès Nancy France; Groupe Hospitalier privé Ambroise Paré Hartmann Paris IBD Center 92200 Neuilly sur Seine France; Division of Gastroenterology and Hepatology McGill University Health Centre Montreal Quebec Canada

Department of Medicine 1 Agaplesion Markus Hospital Goethe University Frankfurt Germany

Division of Gastroenterology Hepatology and Endoscopy Brigham and Women's Hospital Harvard Medical School Boston Massachusetts

Dr Henry D Janowitz Division of Gastroenterology Icahn School of Medicine at Mount Sinai New York New York

Hospital Clínic de Barcelona IDIBAPS CIBERehd Barcelona Spain

Janssen Research and Development LLC Spring House Pennsylvania

Kyorin University Tokyo Japan

University of British Columbia Vancouver British Columbia Canada

University of California San Diego La Jolla California

University of Chicago Medicine Inflammatory Bowel Disease Center Chicago Illinois

University of Pennsylvania Health System The Raymond and Ruth Perelman School of Medicine of the University of Pennsylvania Gastroenterology Division Philadelphia Pennsylvania

Western University London Ontario Canada

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ClinicalTrials.gov
NCT04033445