B0406 - Mirikizumab Demonstrates Sustained Improvement in Fatigue in Patients with Moderately-to-Severely Active Ulcerative Colitis: Results From the Phase 3 LUCENT-1 Induction and LUCENT-2 Maintenance Studies
Introduction: Fatigue is a significant concern for patients (pts) with ulcerative colitis (UC).1 Mirikizumab (miri), an anti-IL-23p19 monoclonal antibody, demonstrated efficacy vs placebo (PBO) in adult pts with moderately-to-severely active UC in phase 3, randomized, double-blind, PBO-controlled 12-week (W) induction (LUCENT-1/NCT03518086) and 40-W maintenance (LUCENT-2/NCT03524092) studies.2,3 Here, we report the effect of miri vs PBO on fatigue.
Methods: In the induction study, pts (N=1162) were randomized (3:1) to intravenous (IV) miri 300 mg or PBO every 4 weeks (Q4W). Pts who achieved clinical response with miri at W12 (N=544) in the induction were re-randomized (2:1) to subcutaneous (SC) miri 200 mg or PBO Q4W through W40 in the maintenance study. Fatigue was measured using the Fatigue Numeric Rating Scale (NRS), a single-question patient-reported instrument that measures the “worst fatigue in the past 24 hours” with an 11-point NRS (0 = no fatigue, 10 = fatigue as bad as you can imagine), on an electronic daily diary in LUCENT-1 and W40 of LUCENT-2 studies. The treatment difference in least squares mean (LSM) change from the baseline (W0 of therapy) in Fatigue NRS scores was determined using the analysis of covariance model.
Results: In the induction study, a significant reduction in Fatigue NRS score vs PBO was observed as early as W2 (LSM difference [95% CI]: −0.25 [−0.45, −0.05], p=0.013). The LSM difference from baseline at W12 was −0.69 (−0.98, −0.40; p< 0.001). In the maintenance study, a significant reduction in Fatigue NRS score compared to PBO was observed from W16 and sustained through W40 (−1.10 [−1.53, −0.67]; p< 0.001; Figure).
Discussion: Miri-treated pts with moderately-to-severely active UC showed early (W2) and sustained (W40) improvements in fatigue compared to PBO.
1Huppertz-Hauss G, et al. Fatigue in a population-based cohort of patients with inflammatory bowel disease 20 years after diagnosis: the IBSEN study. Scand J Gastroenterol. 2017;52:351–358.
2G D’Haens, et al. Efficacy and safety of mirikizumab as induction therapy in patients with moderately to severely active Ulcerative Colitis: Results from the Phase 3 LUCENT-1 study. J Crohn's Colitis. 2022;16:i028–29.
3M Dubinsky, et al. Efficacy and safety of mirikizumab as maintenance therapy in patients with moderately to severely active ulcerative colitis: results from the phase 3 LUCENT-2 study. Abs. 867e. Digestive Disease Week, May 21-24, 2022.
