S755 Early Symptom Control With Mirikizumab in Patients With Moderately to Severely Active Ulcerative Colitis in the LUCENT-1 Induction Trial

Abstract

Introduction: Mirikizumab (miri), an anti-IL23/p19 monoclonal antibody, demonstrated efficacy compared with placebo (PBO) in the Phase 3, multicentre, randomized, double-blind LUCENT-1 induction study in patients with moderately to severely active ulcerative colitis (UC, NCT03518086)). This analysis assessed early onset of symptomatic improvement and symptomatic control during induction. Methods: During the 12-week (W) induction study, 1162 adult patients (pts) with inadequate response, loss of response, or were intolerant to conventional therapy or biologic or tofacitinib therapy for UC, received miri IV Q4W (N=868) or PBO (N=294). We evaluated improvement for symptoms of stool frequency (SF), rectal bleeding (RB) and bowel movement urgency (BU), abdominal pain and fatigue. BU Numeric Rating Scale (NRS) change from baseline (BL), BU Clinical Meaningful Improvement (CMI), BU Remission, Fatigue NRS change from BL, Abdominal Pain Improvement, as well as SF Remission, RB Remission, Symptomatic Response and Symptomatic Remission were assessed. Results: As early as W2, miri-treated pts achieved a significantly greater reduction in RB subscores (p=0.001) and in SF subscores (p=0.035). From W2 and W4, a significantly greater percentage achieved SF Remission and RB Remission, respectively compared to PBO. A significantly greater percentage of miri-treated pts achieved Symptomatic Response compared to PBO from W2 (p=0.003) and of Symptomatic Remission compared with PBO from W4 (p< 0.001). Miri-treated pts showed a significantly greater mean reduction in BU NRS scores as early as W2 compared to PBO (p=0.004). From W4, a significantly greater percentage of miri-treated pts achieved BU CMI versus PBO (p=0.044). From W7 onwards, a significantly greater percentage achieved BU Remission (p=0.002). The pts showed a significantly greater mean reduction in Fatigue NRS scores from W2 compared to PBO (p=0.014). As early as W4, a significant reduction of at least 30% in Abdominal Pain NRS score from BL was observed in the miri-treated pts compared with PBO (p=0.007). At W12, a significantly greater proportion of miri-treated pts achieved Symptomatic Response, Symptomatic Remission, RB Remission, SF Remission, BU change from BL, BU CMI and Remission, as well as Fatigue and Abdominal Pain Improvement, compared to PBO (Table). Conclusion: Miri provides rapid control of UC symptoms, including BU and fatigue, as early as W2 compared with PBO in pts with moderately to severely active UC. Table 1. - Assessment of improvement for UC symptomatic components in patients treated with miri vs PBO at W12 Endpoint (W12) PBO IVQ4WN=294 Miri 300 mg IVQ4WN=868 Risk difference vs PBO (95% CI) * P-value RB Remission a , n (%) 129 (43.9) 555 (63.9) 20.6 (14.2, 27.0) < 0.001 SF Remission b , n (%) 117 (39.8) 495 (57.0) 17.1 (10.7, 23.6) < 0.001 Symptomatic Response c , n (%)Symptomatic Remission d , n (%) 154 (52.4)82 (27.9) 625 (72.0)395 (45.5) 20.2 (13.8, 26.6)17.5 (11.4, 23.6) < 0.001< 0.001 BU Clinical Meaningful Improvement e , n (%) N=276** 89 (32.2) N=811** 395 (48.7) 16.2 (9.7, 22.7) < 0.001 BU Remission f , n (%) N=276** 34 (12.3) N=811** 179 (22.1) 9.7 (4.9, 14.5) < 0.001 BU NRS, LSM change from baseline (SE)Fatigue NRS, LSM change from baseline (SE) -1.63 (0.14)-1.29 (0.13) -2.59 (0.08)-1.96 (0.08) -0.95 (-1.47, -0.44)-0.66 (-0.96, -0.37) < 0.001< 0.001 Abdominal Pain NRS ≥30% reduction g , n (%) N=246** 121 (49.2) N=711** 472 (66.4) 17.4 (10.3, 24.6) < 0.001 *The Cochran-Mantel-Haenszel (CMH) test, with missing data imputed as nonresponse, was used to assess the outcomes. Mixed Model for Repeated Measures was used to assess BU NRS. The risk difference and CMH test were both adjusted for the stratification factors of prior biologic or tofacitinib failure, baseline corticosteroid use, region, and baseline modified mayo score.**Baseline population differs according to definition of each endpoint.aRB subscore of 0.bSF subscore 0, or 1 with ≥1-point decrease from BL.cAt least a 30% decrease from BL in the sum of SF and RB subscores.dSF subscore 0, or 1 with ≥1-point decrease from BL, and RB subscore of 0.eBU NRS improvement of ≥3 points pts with BL BU NRS ≥3.fNRS 0 or 1 in pts with BL BU NRS ≥3.gNRS pain score ≥30% improvement from baseline in patients with baseline AP NRS ≥3.Abbreviations: PBO= placebo; miri= mirikizumab; Q4W= every 4 weeks; CI= confidence interval; n= number of patients in the specified category, RB= rectal bleeding; LSM = least square mean; SE= standard error; SF= stool frequency; BU= bowel movement urgency; NRS = numeric rating scale.