S903 Cumulative Response to Guselkumab Through Week 24 of Induction in Patients With Moderately to Severely Active Ulcerative Colitis: Results From the Phase 3 QUASAR Induction Study

Introduction: The Phase 3 QUASAR induction study evaluated efficacy and safety of guselkumab (GUS), an IL-23p19 subunit antagonist, in patients (pts) with moderately to severely active UC. At Week (Wk) 12, GUS 200mg IV was more effective than placebo (PBO) in inducing clinical remission and clinical response. Pts not in clinical response at Wk12 received GUS through Wk24. Here, we report GUS cumulative efficacy and safety. Methods: Pts with a modified Mayo score of 5-9 and a centrally reviewed Mayo endoscopy subscore ≥2 at baseline (BL) were randomized 3:2 to receive GUS 200mg IV or PBO at Wks0, 4, and 8. Pts not in clinical response at Wk12 received GUS at Wks12, 16, and 20 (GUS 200mg IV→GUS 200mg SC; PBO→GUS 200mg IV) and were evaluated at Wk24. Matching IV or SC PBO were used to maintain study blinding. Final safety assessments were conducted through Wk 32 (ie, 12 wks after last dose of GUS). Results: The primary analysis population consisted of 701 pts. BL demographics were similar among treatment groups, and approximately 50% had a history of inadequate response/intolerance to advanced therapy (ADT-IR). At Wk12, clinical response was achieved by a higher percentage of GUS- vs PBO-treated pts (61.5% vs 27.9%, respectively; adjusted Δ [95% CI]: 33.8% [26.9%, 40.7%]; P< 0.001; Figure 1). Of GUS-treated pts who were not in clinical response at Wk12 and received additional GUS treatment (GUS IV→GUS SC), 55% (66/120) achieved clinical response at Wk24. Cumulative clinical response at Wk12 or 24 was achieved by 77.2% of pts randomized to GUS at BL. Pts with and without history of ADT-IR benefitted from continued treatment with GUS SC through Wk24 (51.4% and 60.9% achieved clinical response at Wk24, respectively). Of PBO-treated pts who were not in clinical response at Wk12 and received GUS treatment (PBO IV→GUS IV), clinical response rate at Wk24 (69.7%) was similar to that at Wk12 for pts randomized to GUS at BL (61.5%). Safety findings through the final safety visit were consistent with Wk12 results; no new safety signals were identified (Table 1). The most frequent adverse events among GUS-treated pts (n=586) were COVID-19 (7.2%), anemia (5.1%), and worsening UC (4.6%). Conclusion: Among pts randomized to GUS IV who did not achieve clinical response at Wk12, continued treatment with GUS SC allowed 55% to achieve clinical response at Wk24. Overall, more than three-quarters of pts randomized to GUS IV achieved clinical response at Wk12 or 24. No new safety signals for GUS were identified.Figure 1.: Cumulative clinical response through Week 24. Table 1. - Safety summary through final safety visit IV Induction Cross-over Combined PBO IVa GUS 200mg IVa PBO IV → GUS 200mg IVb GUS 200mg IV → GUS 200mg SCb All GUSc Safety analysis set, N 280 421 165 125 586 Average duration of follow-up (weeks) 12.1 12.3 13.9 14.6 15.9 Average exposure (number of administrations) 2.9 2.9 2.9 2.8 3.5 Deathsd 2 (0.7%) 1 (0.2%) 0 0 1 (0.2%) Patients with one or more: Adverse events 138 (49.3%) 208 (49.4%) 65 (39.4%) 56 (44.8%) 292 (49.8%) Serious adverse events 20 (7.1%) 12 (2.9%) 3 (1.8%) 3 (2.4%) 18 (3.1%) Adverse events leading to discontinuation of study agent 11 (3.9%) 7 (1.7%) 7 (4.2%) 5 (4.0%) 19 (3.2%) Infectionse 43 (15.4%) 67 (15.9%) 26 (15.8%) 18 (14.4%) 104 (17.7%) Serious infectionse 1 (0.4%) 3 (0.7%) 1 (0.6%) 2 (1.6%) 6 (1.0%) Adverse events within 1 hour of infusionf 1 (0.4%) 6 (1.4%) 1 (0.6%) 3 (2.4%) 10 (1.7%) Note: Includes only pts with modified Mayo score 5-9 at induction baseline.aIncludes data up to Week 12 for subjects who received treatment at Week 12. Includes all data through final safety visit (12 weeks after the last dose of study intervention) for subjects who did not receive treatment at Week 12.bIncludes data from Week 12 onward.cFrom the first guselkumab dose onward.dAll reported deaths were cardiovascular in nature and the patient in GUS arm had substantial cardiovascular risk factors.eInfections were defined as any adverse event which was coded to the MedDRA system organ class 'Infections and infestations.’fNo AEs within 1 hour of infusion were serious or resulted in treatment discontinuation.

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