Efficacy and safety of subcutaneous guselkumab induction therapy in patients with ulcerative colitis: results through week 24 from the phase 3 ASTRO study

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Introduction: Guselkumab (GUS), a dual-acting IL-23p19 subunit inhibitor, demonstrated efficacy in patients (pts) with ulcerative colitis (UC) treated with GUS intravenous (IV) induction and subcutaneous (SC) maintenance (QUASAR). Objectives: To evaluate GUS SC induction efficacy and safety in ASTRO, phase 3, randomized, double-blind, placebo (PBO)-controlled, parallel-group, multicenter trial in moderately to severely active UC. Methodology: Eligible pts had inadequate response/intolerance to corticosteroids, immunosuppressants, biologics, JAK inhibitors, and/or S1P inhibitors (BIO/JAKi/S1Pi-IR)/were BIO/JAKi/S1Pi-naïve. Randomization was stratified by baseline (BL) BIO/JAKi/S1Pi status, Mayo endoscopic subscore (MES); 418 pts allocated 1:1:1 to GUS 400mg SC (q4w; x3)→GUS 200mg SC q4w (N=140), GUS 400mg SC q4w (x3)→GUS 100mg SC q8w (N=139)/PBO (N=139). Pts were rescued at week (W)16: PBO switched to GUS; GUS stayed on GUS (sham rescue). Primary endpoint: W12 clinical remission. Multiplicity-controlled secondary endpoints: clinical remission at W24; symptomatic remission, endoscopic improvement, clinical response: all W12 and W24; histo-endoscopic mucosal improvement (HEMI) at W12. Prespecified analysis compared combined GUS 400mg SC vs PBO at W12, each GUS SC maintenance regimen vs PBO at W24. Safety was assessed throughout. Results: BL characteristics were similar across groups (overall mean age, 41.7yrs; mean UC duration, 7.6yrs; mean modified Mayo score, 6.7; MES=3, 56.0%; BIO/JAKi/S1Pi-IR, 40.2%). The primary and all secondary endpoints were met. At W12, greater proportions of GUS- vs PBO-treated pts achieved clinical remission (27.6% vs 6.5%), symptomatic remission (51.3% vs 20.9%), endoscopic improvement (37.3% vs 12.9%), clinical response (65.6% vs 34.5%), HEMI (30.5% vs 10.8%); all P<0.001. At W24, greater proportions of pts treated with GUS 100mg SC q8w/GUS 200mg SC q4w vs PBO achieved clinical remission (35.3% and 36.4% vs 9.4%;both P<0.001), symptomatic remission (54.7% and 50.0% vs 25.2%;both P<0.001), endoscopic improvement (40.3% and 45.0% vs 12.2%;both P<0.001), clinical response (63.3% and 61.4% vs 30.9%;both P<0.001). In subgroups by BIO/JAKi/S1Pi history, greater proportions of GUS- vs PBO-treated pts achieved endpoints ([ Fig. 1 ]). Fig. 1 Proportions of GUS vs PBO pts with≥1 AE, serious AE, AE leading to treatment discontinuation were not greater (Table). Conclusion: ASTRO established efficacy of GUS SC induction in UC with no new safety concerns ([ Fig. 2 ]). Fig. 2 Publication History Article published online: 04 September 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

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