S1586 Efficacy of Guselkumab in Moderately to Severely Active Ulcerative Colitis by Extent of Disease and Inflammatory Burden: Subgroup Analysis of the Phase 3 QUASAR Maintenance Study

Introduction: Guselkumab (GUS) is a dual-acting IL-23 inhibitor. In the Phase 3 QUASAR maintenance study (NCT04033445), both the GUS 100 mg every 8 weeks (every 8 weeks) and 200 mg every 4 weeks subcutaneous (SC) maintenance dose regimens were efficacious. Here, we evaluated efficacy of these dose regimens in clinically relevant subgroups of participants (pts) with and without extensive ulcerative colitis (UC) disease or high inflammatory burden. Methods: Clinical responders after 12 weeks of GUS intravenous (IV) induction were randomized 1:1:1 to GUS 100 mg SC every 8 weeks, GUS 200 mg SC every 4 weeks or placebo (PBO) (GUS withdrawal) at start of the maintenance study (M-0). Efficacy endpoints were analyzed at Week (W)44 in the primary analysis population of pts randomized and treated in the maintenance study who had a modified Mayo score of 5-9 at induction baseline (I-0). Subgroup analyses were conducted by (1) extent of UC disease (limited to left side of colon vs extensive) based on screening endoscopy and/or medical history at I-0 and (2) inflammatory burden based on serum C-reactive protein (CRP) levels (≤3 vs >3 mg/L) at M-0. Results: Of 568 pts in the primary analysis population, 257 (45.2%) had extensive UC disease at I-0 and 182 (32.0%) had serum CRP >3 mg/L at M-0. Proportions of pts achieving W44 clinical and histologic-endoscopic efficacy endpoints were greater with both GUS dose regimens vs PBO across subgroups. For pts with extensive UC disease, the proportion of pts achieving clinical remission at W44 was numerically greater with GUS 200 mg every 4 weeks (62.7%) relative to GUS 100 mg every 8 weeks (49.4%) (PBO, 11.6%). For those with elevated CRP (>3 mg/L) at M-0, clinical remission at W44 was achieved by 48.2% of GUS 200 mg every 4 weeks vs 30.2% of GUS 100 mg every 8 weeks pts (PBO, 14.3%). Proportions of pts achieving endoscopic improvement, histo-endoscopic improvement, endoscopic remission, and maintenance of clinical remission were also greater with GUS 200 mg every 4 weeks in these subgroups. Among pts with disease limited to the left side of the colon or CRP ≤3 mg/L at M-0, proportions of pts achieving these efficacy endpoints were similar with GUS 100 mg every 8 weeks and GUS 200 mg every 4 weeks. Conclusion: For pts with moderately to severely active UC with extensive disease or high inflammatory burden, greater efficacy rates were observed with GUS 200 mg SC every 4 weeks compared with GUS 100 mg SC every 8 weeks.