Guselkumab in East Asians With Moderate-to-Severe Ulcerative Colitis: Subgroup Analysis of the QUASAR Induction and Maintenance Studies

Abstract

Background and aim: The global QUASAR (NCT04033445) clinical program demonstrated the efficacy and safety of guselkumab, a dual-acting interleukin-23 p19 subunit inhibitor, as induction and maintenance therapy in participants with moderate to severely active ulcerative colitis (UC). We report a subgroup analysis in East Asian participants.

Methods: The QUASAR program included two randomized, placebo-controlled, 12-week induction studies of guselkumab 200 mg (and 400 mg, Phase 2b) IV every 4 weeks (q4w) in adults with baseline modified Mayo scores of 5-9 and inadequate response/intolerance to conventional and/or advanced UC therapy. Clinical responders to guselkumab induction were re-randomized (1:1:1) at maintenance study baseline to SC guselkumab 200 mg q4w, 100 mg q8w, or placebo. Primary endpoints were clinical response (Phase 2b) or clinical remission (Phase 3) at induction Week 12 (I-12) and clinical remission at maintenance Week 44 (M-44). Subgroup analyses included participants from sites in China, Japan, Korea, and Taiwan region.

Results: Data were from 71 (Phase 2b) and 135 (Phase 3) East Asians in the induction studies and 106 in the maintenance study. At Week I-12, 45.5%-58.8% of guselkumab versus 25.5%-29.2% of placebo participants achieved clinical response and 16.0%-23.8% versus 4.2%-5.5%, respectively, achieved clinical remission. At Week M-44, 37.1%-46.3% of guselkumab versus 13.3% of placebo participants achieved clinical remission. The adverse event profile was generally consistent with the global QUASAR population.

Conclusions: Results support the efficacy and safety of guselkumab induction and maintenance in East Asians with moderately to severely active UC, consistent with findings from the global QUASAR studies.

Trial registration: ClinicalTrials.gov, NCT04033445; EudraCT, 2018-004002-25.

Keywords: Asia; clinical trials; guselkumab; ulcerative colitis.

FIGURE 1

Overview of the QUASAR Phase 2b/3 clinical trial program of guselkumab in ulcerative colitis. Footnote: GUS, guselkumab; IV, intravenous; q4w, every 4 weeks; q8w, every 8 weeks; SC, subcutaneous; UC, ulcerative colitis. *Study treatment administered; ^†Study treatment administered to Week 12 clinical non‐responders at weeks 12, 16, and 20. ^aClinical response defined as a decrease from induction baseline in the modified Mayo score by ≥ 30% and ≥ 2 points, with either a ≥ 1 point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1.

FIGURE 2

Participant disposition in the QUASAR induction studies and maintenance study (East Asian subpopulation)^a. Footnote: FAS, Full Analysis Set; GUS, guselkumab; IV, intravenous; M‐0, maintenance Week 0; q4w, every 4 weeks; q8w, every 8 weeks; SC, subcutaneous. ^aIncludes only participants with a modified Mayo score 5–9 at induction baseline (primary analysis population). ^bMaintenance study disposition is shown for participants randomized at Week M‐0; an additional 23 induction placebo IV responders and 30 induction guselkumab 24‐week responders continued in the non‐rerandomized portion of maintenance study to receive placebo SC or GUS 200 mg SC q4w, respectively.

FIGURE 3

Summary of primary and major secondary efficacy outcomes in the Phase 2b and Phase 3 QUASAR induction studies (East Asian subpopulation versus global population). Footnote: AE, adverse event; GUS, guselkumab; I‐0, induction Week 0; I‐12, induction Week 12; IBDQ, Inflammatory Bowel Disease Questionnaire; IV, intravenous; PRO, patient‐reported outcome; PROMIS, Patient‐Reported Outcomes Measurement Information System; pts, participants. Includes only participants with modified Mayo score 5–9 at induction baseline. Data for global participants have been reported previously [23, 24]. Clinical response is defined as a decrease from induction baseline in the modified Mayo score by ≥ 30% and ≥ 2 points, with either a ≥ 1‐point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1. Clinical remission is defined as a stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy, where the stool frequency subscore has not increased from induction baseline. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1 with no friability present on the endoscopy. Histologic‐endoscopic mucosal improvement is defined as achieving a combination of histologic improvement and endoscopic improvement. Histologic improvement is defined as neutrophil infiltration in < 5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue according to the Geboes grading system. Endoscopic remission (normalization) is defined as an endoscopy subscore of 0. Histologic remission is defined as absence of neutrophils from the mucosa (both lamina propria and epithelium), no crypt destruction, and no erosions, ulcerations or granulation tissue according to the Geboes grading system. Symptomatic remission is defined as a stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0, where the stool frequency subscore has not increased from induction baseline. IBDQ remission is defined as a total IBDQ score ≥ 170. Fatigue response is defined as ≥ 7‐point improvement from induction baseline in the PROMIS‐Fatigue Short Form 7a.

FIGURE 4

Summary of primary and major secondary efficacy outcomes in the Phase 3 QUASAR maintenance study (East Asian subpopulation). Footnote: AE, adverse event; GUS, guselkumab; IBDQ, Inflammatory Bowel Disease Questionnaire; M‐0, maintenance Week 0; M‐44, maintenance Week 44; PRO, patient‐reported outcome; PROMIS, Patient‐Reported Outcomes Measurement Information System; pts, participants; q4w, every 4 weeks; q8w, every 8 weeks; SC, subcutaneous. Includes only participants with modified Mayo score 5–9 at induction baseline. Data for global participants have been reported previously [24]. Clinical response is defined as a decrease from induction baseline in the modified Mayo score by ≥ 30% and ≥ 2 points, with either a ≥ 1‐point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1. Clinical remission is defined as a stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy, where the stool frequency subscore has not increased from induction baseline. Symptomatic remission is defined as a stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0, where the stool frequency subscore has not increased from induction baseline. Corticosteroid‐free clinical remission is defined as not requiring any treatment with corticosteroids for at least 8 weeks prior to Week M‐44 and also meeting the criteria for clinical remission at Week M‐44. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1 with no friability present on the endoscopy. Histologic‐endoscopic mucosal improvement is defined as achieving a combination of histologic improvement and endoscopic improvement. Histologic improvement is defined as neutrophil infiltration in < 5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue according to the Geboes grading system. Endoscopic remission (normalization) is defined as an endoscopy subscore of 0. IBDQ remission is defined as a total IBDQ score ≥ 170. Fatigue response is defined as ≥ 7‐point improvement from induction baseline in the PROMIS‐Fatigue Short Form 7a.