Guselkumab in Patients With Moderately to Severely Active Ulcerative Colitis: QUASAR Phase 2b Induction Study.

Abstract

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.

• Authors: Laurent Peyrin-Biroulet, Jessica R Allegretti, David T Rubin, Brian Bressler, Matthew Germinaro, Kuan-Hsiang Gary Huang, Nicole Shipitofsky, Hongyan Zhang, Rebbecca Wilson, Chenglong Han, Brian G Feagan, William J Sandborn, Julian Panés, Tadakazu Hisamatsu, Gary R Lichtenstein, Bruce E Sands, Axel Dignass, QUASAR Study Group
• Journal: Gastroenterology (Gastroenterology) Vol. 165 Issue 6 Pg. 1443-1457 (Dec 2023) ISSN: 1528-0012 [Electronic] United States
• PMID: 37659673 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• guselkumab
• Immunosuppressive Agents

Topics

• Humans
• Antibodies, Monoclonal, Humanized (adverse effects)
• Colitis, Ulcerative (diagnosis, drug therapy, complications)
• Double-Blind Method
• Immunosuppressive Agents (therapeutic use)
• Remission Induction
• Treatment Outcome