OP10 Efficacy and safety of subcutaneous guselkumab induction therapy in patients with Ulcerative Colitis: Results through week 12 from the phase 3 ASTRO study

Guselkumab (GUS) is a selective dual-acting IL-23p19 subunit inhibitor that potently blocks IL-23 and binds to CD64, a receptor on cells that produce IL-23. GUS demonstrated efficacy in patients (pts) with ulcerative colitis (UC) who received GUS intravenous (IV) induction and subcutaneous (SC) maintenance (QUASAR). We evaluated the efficacy and safety of GUS SC induction in ASTRO, a phase 3, randomised, double-blind, placebo (PBO)-controlled, parallel-group, multicenter trial in pts with moderately to severely active UC. Eligible pts had a history of inadequate response or intolerance to corticosteroids, immunosuppressants, biologics, Janus kinase inhibitors, and/or sphingosine 1-phosphate inhibitors (BIO/JAKi/S1Pi-IR) or were BIO/JAKi/S1Pi naïve. Randomisation was stratified by baseline (BL) BIO/JAKi/S1Pi status and Mayo endoscopic subscore (MES) with 418 pts allocated 1:1:1 to GUS 400 mg SC q4w (x3)→GUS 200 mg SC q4w (N=140), GUS 400 mg SC q4w (x3)→GUS 100 mg SC q8w (N=139), or PBO (N=139). The primary endpoint was clinical remission (Mayo stool frequency subscore 0/1 not increased from BL, rectal bleeding subscore 0, MES 0/1 with no friability) at week (W) 12. Multiplicity-controlled W12 secondary endpoints are clinical response, symptomatic remission, endoscopic improvement, and histo-endoscopic mucosal improvement (HEMI). The prespecified analysis plan compared the combined GUS 400 mg SC treatment group to PBO at W12, and safety was assessed throughout. BL characteristics were similar across treatment groups (overall mean age, 41.7 years; mean UC duration, 7.6 years; mean modified Mayo score, 6.7; MES=3, 56.0%; BIO/JAKi/S1Pi-IR, 40.2%). The primary endpoint and all secondary endpoints were met. At W12, significantly greater proportions of pts treated with GUS 400 mg SC induction than PBO achieved clinical remission (27.6% vs 6.5%, respectively; adj Δ: 21.1%; P<0.001), clinical response (65.6% vs 34.5%; adj Δ: 31.0%; P<0.001), symptomatic remission (51.3% vs 20.9%; adj Δ: 30.4%; P<0.001), endoscopic improvement (37.3% vs 12.9%; adj Δ: 24.3%; P<0.001), and HEMI (30.5% vs 10.8%; adj Δ: 19.6%; P<0.001). In prespecified analyses of subpopulations defined by prior BIO/JAKi/S1Pi history, greater proportions of GUS-treated versus PBO-treated pts achieved the endpoints (Figure). The proportions of GUS-treated pts with ≥1 adverse event (AE), serious AE, or AE leading to treatment discontinuation were not greater than PBO (Table). ASTRO established the efficacy of GUS SC induction in UC, with no new safety concerns identified. These results build on the QUASAR IV induction data, demonstrating that both GUS IV and SC induction are highly efficacious in pts with moderately to severely active UC.