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Introduction Guselkumab (GUS) is a dual-acting IL-23p19 inhibitor that potently neutralizes IL-23 and binds to CD64, a receptor on cells that produce IL-23. 1 In the Phase 3 QUASAR maintenance study (NCT04033445), both the GUS 100mg every 8 weeks (q8w) and 200mg q4w subcutaneous (SC) maintenance dose regimens were efficacious.2 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 100mg SC q8w, GUS 200mg SC q4w 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 >3mg/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 >3mg/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 200mg q4w (62.7%) relative to GUS 100mg q8w (49.4%) (PBO, 11.6%). For those with elevated CRP (>3mg/L) at M-0, clinical remission at W44 was achieved by 48.2% of GUS 200mg q4w vs 30.2% of GUS 100mg q8w 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 200mg q4w in these subgroups. Among pts with disease limited to the left side of the colon or CRP ≤3mg/L at M-0, proportions of pts achieving these efficacy endpoints were similar with GUS 100mg q8w and GUS 200mg q4w.Conclusions For pts with moderately to severely active UC with extensive disease or high inflammatory burden, greater efficacy rates were observed with GUS 200mg SC q4w compared with GUS 100mg SC q8w.Study support Johnson & Johnson.References Sachen KL, et al. Guselkumab binding to CD64+ IL-23–producing myeloid cells enhances potency for neutralizing IL-23 signaling. Front. Immunol. 2025;16:1532852.Rubin DT, et al. Guselkumab in patients with moderately to severely active ulcerative colitis (QUASAR): phase 3 double-blind, randomised, placebo-controlled induction and maintenance studies. Lancet. 2025;405(10472):33–49.