Guselkumab in Patients With Moderately to Severely Active Ulcerative Colitis: QUASAR Phase 2b Induction Study
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, Julián Panés, Tadakazu Hisamatsu, Gary R. Lichtenstein, Bruce E. Sands, Axel Dignaß, О. Аbrahamovych, Halyna Afanasieva, Lilia Aitova, Engin Altıntaş, Romain Altwegg, П. С. Андреев, Kazuki Aomatsu, Monika Augustyn, Paola Balestrieri, Jakob Begun, Luciana Soledad Brunatto, Diego Bulgheroni, Elena Bunkova, Mercedes Cabello, Qian Cao, Flavio Caprioli, Rute Cerqueira, Baili Chen, Chou‐Chen Chen, Chou-Pin Chen, Cheng‐Tang Chiu, Chang Hwan Choi, Michele Cicala, Olena Datsenko, Pieter Dewint, Eugeni Domènech, Joris Dutré, George Duvall, J. C. Fernández, Rafał Filip, Ronald Fogel, Sharyle Fowler, Toshimitsu Fujii, Masayuki Fukata, Yohei Furumoto, Antonio Gasbarrini, Beata Gawdis-Wojnarska, Cyrielle Gilletta, Paolo Gionchetti, Eran Goldin, Oleksandr Golovchenko, Maciej Gonciarz, Can Gönen, Gaston Gonzalez Segura, Oleksii Gridnyev, T Gyökeres, Xavier Hébuterne, Charlotte Hedin, Per M. Hellström, Ida Hilmi, Ivo Horný, Gyula Horvat, Namiko Hoshi, Luděk Hrdlička, Shunji Ishihara, Olha Ivanishyn, Byung Ik Jang, Odery Junior, Takashi Kagaya, Shuji Kanmura, Marina Karakina, Nakai Katsuhiko, Jarosław Kierkuś, Hyo Jong Kim, Tae-Oh Kim, Young‐Ho Kim, G Kiss, Jochen Klaus, D Kleczkowski, Maria Kłopocka, Taku Kobayashi, Iwona Kobielusz‐Gembala, Ja Seol Koo, Adam Kopoń, Tetiana Kravchenko, Masatoshi Kudo, Kwang An Kwon, Paula Lago, David Laharie, Ian C. Lawrance, Jarosław Leszczyszyn, Yan Li, Milan Lukáš
Abstract
Background & AimsThe 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.MethodsIn 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).ResultsThe 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.ConclusionsGuselkumab 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. 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. 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). 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. 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.