Abstract
BACKGROUND AND AIMS: Comprehensive disease control is an important yet elusive treatment goal in ulcerative colitis (UC). We evaluated the effect of upadacitinib induction and maintenance treatment on composite clinical endpoints and normalization of important health-related quality of life (HRQoL) outcomes. METHODS: Data from the U-ACHIEVE and U-ACCOMPLISH trials were analyzed. Clinical responders to upadacitinib 45 mg 8-week induction were re-randomized 1:1:1 to upadacitinib 30 mg, 15 mg, or placebo for 52 weeks of maintenance. The percentage of patients achieving a composite clinical endpoint (clinical remission, complete symptom resolution, and Inflammatory Bowel Disease Questionnaire [IBDQ] remission) and a composite endpoint for normalization of HRQoL outcomes (Functional Assessment of Chronic Illness Therapy-Fatigue, IBDQ remission, Work Productivity and Activity Impairment Questionnaire-Ulcerative Colitis, 36-item Short Form Survey Physical Component Summary and Mental Component Survey, and EuroQol 5-Dimension 5-Level scores) was evaluated. RESULTS: At induction week 8, more patients treated with upadacitinib 45 mg achieved the composite clinical endpoint vs placebo (6.4% vs 0.9%, P ≤ .001) and normalization of the composite HRQoL endpoint (18.9% vs 5.5%, P ≤ .001). At maintenance week 52, the composite clinical endpoint was achieved by 18.3% and 13.1% of patients treated with upadacitinib 30 mg and 15 mg, respectively, vs 4.5% with placebo (P ≤ .001). Normalization of the composite HRQoL endpoint was achieved by 24.0% and 22.3% of patients treated with upadacitinib 30 mg and 15 mg, respectively, vs 8.7% for placebo (P ≤ .001). CONCLUSIONS: Upadacitinib may help patients with moderately to severely active UC achieve complete symptom resolution, endoscopic remission, and normalization of HRQoL. CLINICAL REGISTRATION NUMBERS: U-ACHIEVE (NCT02819635) and U-ACCOMPLISH (NCT03653026).