S1588 Mirikizumab Sustains Improvement in Fatigue, Abdominal Pain, and Stool Frequency Following 104 Weeks of Continuous Treatment for Crohn’s Disease: Results From the VIVID-2 Open-Label Extension Study

Introduction: Mirikizumab (MIRI), a p19-directed antibody against interleukin-23, demonstrated improvements in fatigue, abdominal pain (AP) and stool frequency (SF) at Week (W) 12 and W52 in the VIVID-1 clinical trial. Methods: This analysis shows the effect of MIRI on fatigue, AP, SF and achievement of clinical remission by Patient-Reported Outcome (PRO; SF ≤3 and AP ≤1 and neither worse than baseline) in the VIVID-2 open-label extension study through W104. This analysis includes data from primary analysis set in patients with Crohn’s disease (CD) randomized to the MIRI treatment arm in VIVID-1 who achieved endoscopic response (≥50% reduction from baseline in Simple endoscopic score for CD) at W52 and continued the MIRI subcutaneous dosing (300 mg) in VIVID-2. Change from VIVID-1 baseline was measured for continuous endpoints. Endpoints: fatigue measured using FACIT-Fatigue (measured as change from baseline, and clinically-meaningful improvement of ≥6-points among patients with baseline ≤46), AP improvement (measured as change from baseline, and achievement of ≤1 among patients with baseline >1), SF improvement (measured as change from baseline, and achievement of ≤3 among patients with baseline >3) and clinical remission by PRO, assessed at W64 and 104. Missing data were handled using observed case (OC) and modified non-responder imputation (mNRI) for response rates, while using modified baseline observation carried forward (mBOCF) for change from baseline. Response rates were presented as unadjusted proportions with 2-sided 95% confidence intervals using the Rubin's Rules (mNRI). ANCOVA models were used for continuous variables, adjusting for baseline values and intervention group. Results: Fatigue mean (standard error [SE]) change from baseline was 10.7 (0.56) at W64; 9.4 (0.59) at W104, (observed response, n [%]: 152 [67.6%] at W64; 136 [64.8%] at W104). AP improved (mean [SE] change: −1.5 [0.04] at W64; −1.6 [0.05] at W104), with response rates increasing from 174 (77.3%) to 161 (84.7%). SF showed sustained improvement (mean [SE] change: −4.3 [0.14] at W64; −4.3 [0.16] at W104), with response rates reaching 155 (89.6%) at W104. Similar rates of achievement of clinical remission by PRO were observed (178 [73.6%] at W64; 165 [80.1%] at W104). Conclusion: MIRI sustained improvement in fatigue, AP, SF and clinical remission by PRO through 104 weeks of continuous treatment. These consistent findings support the long-term treatment with MIRI to address key symptoms of CD.