S1445 Efficacy and Safety of Subcutaneous Guselkumab Induction and Maintenance Therapy in Participants With Ulcerative Colitis: Results Through Week 48 From the Phase 3 ASTRO Study

Introduction: Guselkumab (GUS), a dual-acting interleukin-23p19 subunit inhibitor, demonstrated efficacy in participants (pts) with ulcerative colitis (UC) treated with intravenous (IV) or subcutaneous (SC) induction. Here, we report the efficacy and safety of SC induction followed by SC maintenance through Week (W) 48 in ASTRO, a phase 3, randomized, double-blind, placebo (PBO)-controlled, treat-through study in pts with moderately to severely active UC. Methods: Eligible pts had modified Mayo scores of 5 to 9, rectal bleeding subscore of ≥1, and Mayo endoscopic subscore (MES) ≥2. Pts also had documented inadequate response/intolerance to biologics, Janus kinase (JAK) inhibitors, and/or sphingosine-1-phosphate (S1P) inhibitors (BIO/JAKi/S1Pi-IR) or to corticosteroids, 6-mercaptopurine, or azathioprine. Randomization was stratified by baseline BIO/JAKi/S1Pi-IR status and MES with 418 pts allocated 1:1:1 to GUS 400 mg SC every 4 weeks (every 4 weeks) (×3)→GUS 200 mg SC every 4 weeks (N = 140), GUS 400 mg SC every 4 weeks (×3)→GUS 100 mg SC every 8 weeks (every 8 weeks) (N = 139), or PBO SC (N = 139). PBO pts who met rescue criteria were switched to GUS at W16; GUS pts who met rescue criteria stayed on their assigned GUS dose regimen (sham rescue). Results: At W48, greater proportions of pts in the GUS groups achieved clinical remission compared with PBO (36.7% for GUS 100 mg every 8 weeks [Δ29.5%], 42.9% for GUS 200 mg every 4 weeks [Δ35.6%], 7.2% for PBO). Endoscopic remission proportions were 25.9% for GUS 100 mg every 8 weeks (Δ20.9%), 26.4% for GUS 200 mg every 4 weeks (Δ21.4%), and 5.0% for PBO. Clinical response, symptomatic remission, endoscopic improvement, histologic improvement, and histologic remission proportions were also greater for GUS vs PBO. Consistent with the results of the overall population, efficacy was also observed for subpopulations of BIO/JAKi/S1Pi-naïve and BIO/JAKi/S1Pi-IR pts. Safety events per 100 pts-years were not greater in the GUS groups compared with the PBO group: adverse events (AE) (GUS 100 mg every 8 weeks and 200 mg every 4 weeks vs PBO: 308.3 and 310.7 vs 357.1), serious AEs (6.5 and 8.2 vs 38.4), serious infections (0.8 and 2.5 vs 3.7), and AEs leading to treatment discontinuation (4.9 and 4.1 vs 19.8). Conclusion: GUS SC induction followed by SC maintenance was efficacious through 1 year in pts with moderately to severely active UC, and the safety profile is consistent with GUS in its approved indications including UC.