DOP103 Intravenous and subcutaneous guselkumab induction are similarly efficacious in patients with ulcerative colitis across weight quartile and BMI subgroups: Week 12 results from the phase 3 QUASAR and ASTRO studies

Abstract Background Guselkumab (GUS) is a dual-acting IL-23p19 subunit inhibitor that potently neutralizes IL-23 and binds to CD64, a receptor on cells that produce IL-23.1 The similar efficacy and safety of intravenous (IV) and subcutaneous (SC) induction with GUS in participants with moderately to severely active ulcerative colitis (UC) has been established in the phase 3 QUASAR and ASTRO studies.2,3 Obesity has the potential to impact the pharmacokinetic and pharmacodynamic parameters of subcutaneously administered medications. The aim of this post-hoc analysis was to determine whether body mass and body mass index (BMI) in participants with UC differentially affects the efficacy of GUS SC induction compared to IV induction. Methods Participants had moderately to severely active UC (modified Mayo score of 5-9, baseline Mayo rectal bleeding subscore ≥1, and Mayo endoscopic subscore ≥2) and a history of inadequate response/intolerance to oral corticosteroids, AZA/6-MP/MTX, biologics, Janus kinase inhibitors, and/or sphingosine-1-phosphate (S1P) inhibitors (ASTRO only). GUS phase 3 induction regimens were 200 mg IV in QUASAR (N = 421) or 400 mg SC in ASTRO (N = 279) at Weeks 0, 4, and 8, with matching placebo IV/SC (N = 280 and N = 139, respectively) as the comparator. Clinical response (decrease from 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) and clinical remission (stool frequency subscore of 0 or 1 and not increased from baseline, a rectal bleeding subscore of 0, and an endoscopy subscore of 0, or 1 with no friability present on the endoscopy) were evaluated at Week 12 across baseline weight quartiles and standard BMI subgroups (i.e., underweight [