Guselkumab in Patients With Moderately to Severely Active Ulcerative Colitis : QUASAR Phase 2b Induction Study
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:165 |
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| Enthalten in: |
Gastroenterology - 165(2023), 6 vom: 01. Dez., Seite 1443-1457 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Peyrin-Biroulet, Laurent [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 29.11.2023 Date Revised 29.11.2023 published: Print-Electronic ClinicalTrials.gov: NCT04033445 Citation Status MEDLINE |
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| doi: |
10.1053/j.gastro.2023.08.038 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Guselkumab in Patients With Moderately to Severely Active Ulcerative Colitis |b QUASAR Phase 2b Induction Study |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT04033445 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a CLINICALTRIALS: gov number: NCT04033445 | ||
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Advanced Therapy | |
| 650 | 4 | |a Interleukin-23p19 Subunit Antagonist | |
| 650 | 4 | |a QUASAR | |
| 650 | 4 | |a Ulcerative Colitis | |
| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 650 | 7 | |a guselkumab |2 NLM | |
| 650 | 7 | |a 089658A12D |2 NLM | |
| 650 | 7 | |a Immunosuppressive Agents |2 NLM | |
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| 700 | 1 | |a Germinaro, Matthew |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Kuan-Hsiang Gary |e verfasserin |4 aut | |
| 700 | 1 | |a Shipitofsky, Nicole |e verfasserin |4 aut | |
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| 700 | 1 | |a Feagan, Brian G |e verfasserin |4 aut | |
| 700 | 1 | |a Sandborn, William J |e verfasserin |4 aut | |
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| 700 | 0 | |a QUASAR Study Group |e verfasserin |4 aut | |
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