Sustained Symptom Control With Mirikizumab in Patients With Moderately-to-Severely Active Ulcerative Colitis in the LUCENT-2 Maintenance Trial

Introduction: Mirikizumab (miri) improved symptom control in a Phase 3, multicenter, randomized, double-blind, parallel, placebo-controlled induction study at Week (W)12, in patients (pts) with moderately-to-severely active ulcerative colitis (UC; LUCENT-1). This analysis assessed sustained symptom control during the maintenance phase through W40 (W52 of continuous therapy), among pts who were induced into clinical response with miri. Methods: During the 40W maintenance study (LUCENT-2), pts (N=544) who achieved clinical response to miri 300mg Q4W by W12 of induction, were re-randomized 2:1 to subcutaneous (SC) miri 200mg (n=365) or PBO Q4W (n=179). We evaluated sustained control of stool frequency (SF), rectal bleeding (RB), bowel movement urgency (BU) and abdominal pain (AP). The proportion of pts achieving SF Remission (defined as SF=0, or SF=1 with a ≥1-point decrease from induction baseline [BL]), RB Remission (RB=0), Symptomatic Remission (both SF and RB Remission), Stable Maintenance of Symptomatic Remission (defined as pts in Symptomatic Remission for at least 7 out of 9 visits from W4 to W36 and also at Week 40 among pts in Symptomatic Remission and Clinical Response at the end of LUCENT-1), and AP Improvement (Numeric Rating Scale [NRS] pain score ≥30% improvement from BL in pts with baseline AP NRS ≥3) were assessed. BU NRS change from baseline, and the proportion of pts achieving BU Remission (NRS 0 or 1 in pts with BU NRS ≥3 at baseline) were evaluated. Results: A greater proportion of miri-treated pts achieved SF Remission, RB Remission and Symptomatic Remission compared to PBO at W40 (Table), with significant differences observed from W8 of LUCENT-2 (p=0.042; p=0.004; p=0.036, respectively) and maintained through W40. Miri-treated pts had a significantly higher percentage of Stable Maintenance of Symptomatic Remission (p< 0.001). Pts in the miri-treatment group had a significantly greater mean reduction in BU NRS change from induction BL starting at W12 (p=0.034) onwards compared to PBO (Table). Pts assigned to miri accrued an additional 13.6 percentage-point benefit in BU Remission during the first 8W of maintenance therapy and achieved a significant greater improvement at W40 compared to PBO (p< 0.001, Table). Similarly, AP was significantly improved for the miri-treated group starting at W16 (p=0.034) onwards compared to PBO. Conclusion: Miri provides sustained control of UC symptoms including BU, RB, and SF compared to PBO in pts with moderately to severely active UC. Table 1. - Proportion of Patients with Sustained Symptom Control at Week 40 (LUCENT-2) Endpoint (W40) PBO SC Q4WN=179 Miri 200 mg SC Q4WN=365 Risk difference vs PBO (95% CI)* P-value SF Remission, n (%) 80 (44.7) 274 (75.1) 29.6 (21.2, 38.0) < 0.001 RB Remission, n (%) 89 (49.7) 291 (79.7) 29.1 (20.8, 37.4) < 0.001 Symptomatic Remission, n (%) 71 (39.7) 259 (71.0) 30.2 (21.9, 38.6) < 0.001 Stable Maintenance of Symptomatic Remission, n (%) N=112** 43 (38.4) N=264** 184 (69.7) 31.0 (20.7, 41.2) < 0.001 BU NRS, LSM change from baseline (SE) -2.74 (0.20) -3.80 (0.14) -1.06 (-1.51, -0.61) < 0.001 BU Remission, n (%) N=172** 43 (25.0) N=336** 144 (42.9) 18.1 (9.8, 26.4) < 0.001 AP NRS ≥30% reduction, n (%) N=159** 75 (47.2) N=303** 231 (76.2) 27.4 (18.3, 36.4) < 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 clinical remission status at the end of induction study.**Baseline population differs according to definition of each endpoint.Abbreviations: PBO= placebo; miri= mirikizumab; Q4W= every 4 weeks; CI= confidence interval; n= number of patients in the specified category; SF= stool frequency; RB= rectal bleeding; BU= bowel movement urgency; NRS = numeric rating scale; LSM = least square mean; SE= standard error.