S692 Efficacy and Safety of Upadacitinib Induction Therapy in Patients With Moderately to Severely Active Ulcerative Colitis: Results From the Phase 3 U-ACHIEVE Study

Introduction: U-ACHIEVE is one of two phase 3 induction trials evaluating safety and efficacy of the selective JAK-1 inhibitor upadacitinib-45 mg once daily (UPA) in adults with ulcerative colitis (UC). Methods: U-ACHIEVE, a multicentre, double-blind, placebo (PBO)-controlled trial (NCT02819635) randomized patients (pts) with moderately-to-severely active UC 2:1 to UPA or PBO for 8 weeks (wks). Randomization was stratified by biologic inadequate responder (Biologic-IR) status (Biologic-IR vs non-biologic-IR), baseline corticosteroid use (yes or no), and baseline adapted Mayo score (≤7 or >7). Primary endpoint was proportion of pts achieving clinical remission (per adapted Mayo Score) at wk 8. Ranked secondary endpoints included wk 8 endoscopic improvement, endoscopic remission, clinical response per adapted Mayo Score, and histologic-endoscopic mucosal improvement; and wk 2 clinical response per partial adapted Mayo Score. Non-responder imputation incorporating multiple imputations for missing data due to COVID-19 are reported. Safety was assessed through wk 8. Results: 474 pts were randomized (UPA, n=319; PBO, n=155). Baseline characteristics were well balanced between groups (Table 1). A significantly higher proportion of pts receiving UPA (26.1%) vs PBO (4.8%) achieved wk 8 clinical remission (adjusted treatment difference [95% CI]: 21.6% [15.8, 27.4]; P< 0.001; Figure 1a). For all ranked secondary endpoints, UPA was superior to PBO (P< 0.001; Figure 1a). A significant difference vs PBO in clinical response favouring UPA was seen as early as wk 2 (60.1% vs 27.3%) and was sustained thereafter up to wk 8 (79.0% vs 41.6%; Figure 1b). Serious AEs, severe AEs, and AEs leading to study drug discontinuation were higher in PBO group (Table 1). Acne, creatine phosphokinase elevation, and nasopharyngitis were most common AEs with UPA and worsening UC and anaemia with PBO. Incidence of serious infection was similar between UPA and PBO. Neutropenia and lymphopenia were reported more frequently with UPA vs PBO (Table 1). No adjudicated gastrointestinal perforation, major adverse cardiovascular events, or thrombotic events, and no active tuberculosis, malignancy, or deaths were reported. Conclusion: In pts with moderately-to-severely active UC, UPA induction therapy was superior to PBO in inducing clinical and endoscopic remission/response, over 8 wks; responses were significant and rapid. UPA was well-tolerated; safety was comparable with the known safety profile of UPA, and no new safety signals were identified.Figure 1.: a. Primary and ranked secondary endpoints. b. Clinical response per partial adapted Mayo score.Table 1.: Baseline Demographics and Characteristics and Treatment adverse events throughout 8 weeks.

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