S765 Association of Ulcerative Colitis Bowel Urgency Improvement with Clinical Response and Remission

Introduction: Early bowel movement urgency (BU) improvement association with later clinical endpoint improvements was examined in moderately-to-severely active ulcerative colitis (UC) patients (pts) treated with mirikizumab (miri). Methods: BU was evaluated in Phase 3 randomized placebo (PBO)-controlled 12-week induction (LUCENT-1, NCT03518086) and 40-week maintenance (LUCENT-2, NCT03524092) trials with miri. Pts received IV miri 300mg or PBO during induction. Week (W)12 miri responders were rerandomized at LUCENT-2 baseline (BL) to subcutaneous miri 200mg or PBO. BU was measured with 11-point Urgency Numeric Rating Scale (UNRS) from 0 (no urgency) to 10 (worst possible). Pts’ UNRS scores were an average from 7 consecutive days prior to visit. Association of pts with BU Clinically Meaningful Improvement (CMI) or BU remission between BL and W4 with the proportion of pts achieving clinical response, and clinical, endoscopic, or symptomatic remission at end of W12 was assessed. For pts who achieved clinical response at W12, the analyses were repeated for the end of maintenance based on W12 BU status. Logistic regression models with treatment, urgency (BU CMI or BU Remission), treatment-by-urgency group interaction, and stratification factors were fitted to examine the association between early urgency improvement and later clinical endpoints. Results: Treatment-by-urgency group interactions were not statistically significant across clinical outcomes for induction and maintenance. For induction, treatment and urgency status were statistically significant. Pts experiencing BU CMI or BU remission at W4 were consistently more likely to achieve clinical response, and clinical, endoscopic, or symptomatic remission at W12 for both treatment groups. For remission, only treatment main effect was statistically significant. Among miri induction clinical responders (an enriched population), BU CMI or BU Remission at end of induction (W12) was not associated with later maintenance efficacy outcomes (W52). Miri-treated pts achieved higher rates of clinical response, and clinical, endoscopic, or symptomatic remission at W52 than with PBO regardless of BU CMI or BU Remission at W12 (Table). Conclusion: Early BU Improvement, CMI or Remission, was associated with better clinical outcomes during induction for miri and PBO pts, showing BU is a sensitive predictor of early clinical outcomes. Among miri induction responders, miri consistently provided better maintenance of response and remission rates than PBO. Table 1. - Bowel urgency associations with Clinical Response and Clinical Remission for patients with moderate-to-severely active ulcerative colitis LUCENT-1 Induction Urgency CMI Urgency Remission Endpoint PBO IV (N=276) Miri 300mg IV (N=811) p-value a Endpoint PBO (N=276) Miri 300mg IV (N=811) p-value a Urgency CMI W4 = Yes Clin. Response W12, (%) Clin. Remission W12, (%) Endo. Remission W12, (%) Sympt. Remission W12, (%) n=6168.927.936.149.2 n=23078.737.449.163.5 0.1260.1790.0830.055 Urgency remission W4 = Yes Clin. Response W12, (%) Clin. Remission W12, (%) Endo. Remission W12, (%) Sympt. Remission W12, (%) n=1376.946.246.269.2 n=6581.547.752.370.8 NA b NA b NA b NA b Urgency CMI W4 = No Clin. Response W12, (%) Clin. Remission W12, (%) Endo. Remission W12, (%) Sympt. Remission W12, (%) n=21534.98.816.721.4 n=58157.518.429.638.7 < 0.001< 0.001< 0.001< 0.001 Urgency remission W4 = No Clin. Response W12, (%) Clin. Remission W12, (%) Endo. Remission W12, (%) Sympt. Remission W12, (%) n=26340.711.419.825.5 n=74661.921.733.643.6 < 0.001< 0.001< 0.001< 0.001 LUCENT-2 Maintenance Urgency CMI Urgency Remission Endpoint PBO SC (N=172) Miri 200mg SC (N=336) p-value a Endpoint PBO SC (N=172) Miri 200mg SC (N=336) p-value a Urgency CMI W12 = Yes Clin. Response W52 (%) Clin. Remission W52 (%) Endo. Remission W52 (%) Sympt. Remission W52 (%) n=11252.729.531.343.8 n=21282.553.360.474.1 < 0.001< 0.001< 0.001< 0.001 Urgency remission W12 = Yes Clin. Response W52 (%) Clin. Remission W52 (%) Endo. Remission W52 (%) Sympt. Remission W52 (%) n=5347.234.035.845.3 n=10582.955.261.079.0 < 0.0010.0120.004< 0.001 Urgency CMI W12 = No Clin. Response W52 (%) Clin. Remission W52 (%) Endo. Remission W52 (%) Sympt. Remission W52 (%) n=6045.018.326.735.0 n=12479.047.657.369.4 < 0.001< 0.001< 0.001< 0.001 Urgency remission W12 = No Clin. Response W52 (%) Clin. Remission W52 (%) Endo. Remission W52 (%) Sympt. Remission W52 (%) n=11951.321.826.938.7 n=23180.549.458.469.3 < 0.001< 0.001< 0.001< 0.001 ap-value = within-group treatment comparison from Fisher’s exact tests.bSubgroup N was too small for p-value generation.Urgency CMI: UNRS=≥3 point decrease; Urgency remission: UNRS=0 or 1.Note: Using the Cochran-Mantel-Haenszel (CMH) test, treatment-by-subgroup interactions were not statistically significant.Note: W52 refers to W40 of LUCENT-2, representing 52 weeks of continuous treatment; W12 refers to baseline for LUCENT-2. Abbreviations: CMI=clinically meaningful improvement; PBO=placebo; miri=mirikizumab; IV=intravenous; n=number of patients in the specified category; SC=subcutaneous; W=week.