A0396 - Mirikizumab Improves Mental and Physical Health Outcomes in Patients With Moderately to Severely Active Ulcerative Colitis: Results From the Phase 3 LUCENT-1 Induction and LUCENT-2 Maintenance Studies

Introduction: Mirikizumab (miri), an anti-IL-23p19 monoclonal antibody, demonstrated efficacy vs. placebo (PBO) in adult patients (pts) with moderately to severely active ulcerative colitis (UC) in phase 3, randomized, double-blind, PBO-controlled 12-week (W) induction (LUCENT-1/NCT03518086) and 40-W maintenance (LUCENT-2/NCT03524092) studies.^1,2 Here we evaluated the effect of miri vs. PBO on Medical Outcomes Study 36-Item Short Form Health Survey (SF-36; version 2) scores.

Methods: In the induction study, 1162 pts who had an inadequate response/loss of response/intolerance to conventional/biologic therapy were randomized (3:1) to receive miri 300 mg IV (N=868) or PBO (N=294) every 4 weeks (Q4W). Pts who achieved clinical response with miri at W12 in the induction study (miri clinical responders; N=544) were re-randomized (2:1) to miri 200 mg subcutaneous (N=365) or PBO (N=179) Q4W through W40 (i.e., W52 of continuous therapy) in the maintenance study. Least squares mean (LSM) change from baseline in physical (PCS) and mental (MCS) component scores, and 8 domain scores (physical functioning, role-physical, role-emotional, bodily pain, vitality, social functioning, mental and general health) of the SF-36 survey were evaluated at W12 and W40. Treatment comparisons were made using analysis of covariance.

Results: During the induction period, significant improvements in PCS (LSM difference vs. PBO [95% CI]: 2.07 [1.21, 2.93]; p< 0.001) and MCS (1.60 [0.56, 2.63]; p=0.002), and all domain scores (p< 0.05) of SF-36 were achieved with miri vs. PBO at W12. These improvements in SF-36 scores were sustained throughout the maintenance period with significant improvements seen with miri vs. PBO group in PCS (2.30 [1.12, 3.49]; p< 0.001) and MCS (1.48 [0.13, 2.82]; p=0.031), and 6/8 domain scores (p< 0.05) at W40 (Table).

Discussion: Miri significantly improves SF-36 mental and physical component scores in patients with moderately to severely active UC during induction (W12) and maintenance (W40).

¹G 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(1):i028–i029.

²M 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.