215 Efficacy and Safety of Upadacitinib as an Induction Therapy for Patients With Moderately-to-Severely Active Ulcerative Colitis: Combined Results From 382 Subjects in the Phase 2b Study U-ACHIEVE

Abstract

INTRODUCTION: We assessed efficacy/safety of upadacitinib (UPA) in a ph 2b induction study (part 1) in pts with moderately-to-severely active ulcerative colitis (UC). Additional Pts were enrolled in part 2. We present the efficacy and safety of the combined results of part 1 and part 2 METHODS: Adults with moderately-to-severely active UC (Adapted Mayo Score 5–9 points and centrally-read endoscopy subscore 2–3) were randomised 1:1:1:1:1 to receive extended-release UPA7.5, 15, 30, 45 mg once daily (QD) or placebo for 8 wks (N = 250). In part 2, 132 pts were randomised to UPA30 or 45 mg QD with 1:1 allocation for 8 weeks. Pairwise comparisons between UPA and PBO for primary endpoint of clinical remission per Adapted Mayo Score at Week 8 (defined as stool frequency subscore ≤1, rectal bleeding subscore = 0, and endoscopic subscore ≤1) and ranked secondary endpoints were conducted using Cochran-Mantel-Haenszel test stratified by previous biologic use, BL corticosteroid use, and BL Adapted Mayo score. No multiplicity adjustments were applied. Non-responder imputation was used for missing values in 13% of pts. Treatment emergent adverse events (AEs) were reported from first dose of study drug to up to 30 days after last dose. RESULTS: A total 382 pts were randomised with mean (SD) age of 42.7 (14.3) yrs and disease duration of 8.4 (7.4) yrs. Primary endpoint of clinical remission, and secondary endpoints of endoscopic improvement, clinical response per Adapted Mayo score, clinical response per Partial Mayo score, endoscopic remission, and histologic improvement were significantly higher with UPA doses ≥30 mg QD vs PBO (Table 1). Incidences of AEs were similar across UPA groups and numerically higher in PBO group. Rates of serious AEs were 10.9%, 0%, 4.1%, 4.3% and 4.9% for PBO and UPA 7.5, 15, 30, and 45 mg QD, respectively. Serious infections occurred in pts receiving PBO (4.3%, n = 2), 15 mg QD (2.0%, n = 1), 30 mg QD (0.9%, n = 1), and 45 mg QD (1.6%, n = 2). One case of herpes zoster and pulmonary embolism (PE)/deep vein thrombosis (DVT) with UPA 45 mg QD were reported. PE/DVT was reported 26 days after study drug discontinuation due to UC worsening and hospitalization. No deaths were reported. CONCLUSION: In this combined analysis, primary and ranked secondary endpoints consistently met statistical significance with UPA doses ≥ 30 mg QD vs PBO in pts with moderately-to-severely active UC. These results are consistent with part 1 intention-to-treat analysis.1,2 UPA was well-tolerated and no new safety signals were identified.