P568 Clinical relevance of baseline and change in Urgency Numeric Rating Scale score for mirikizumab treatment for Ulcerative Colitis

Abstract

Abstract Background Mirikizumab (MIRI), an anti-IL-23p19 antibody, has demonstrated efficacy/safety in moderately-to-severely active ulcerative colitis (UC) Phase 3 trials (LUCENT-1 and -2; NCT03518086, NCT03524092). This analysis evaluated induction and maintenance efficacy of MIRI among patients with different baseline (BL) bowel urgency severity. Methods In LUCENT-1, patients were randomized to receive 3 intravenous doses of 300mg MIRI or placebo (PBO); 1 every 4 weeks (Q4W). In LUCENT-2, responders to MIRI induction at W12 were rerandomized to subcutaneous 200mg MIRI or PBO Q4W through W40 (52W continuous treatment). Endpoints: clinical response, clinical remission, endoscopic remission, symptomatic remission at W12 and W52 (definitions in figure legend), Urgency Numeric Rating Scale ([UNRS]: 11-point scale from 0 [no urgency] to 10 [worst possible urgency]). Analysis: Fisher's exact test with non-responder imputation by patient induction BL UNRS score: 0-3, 4-6, and 7-10; score cut-offs based on ≥3 being a clinically meaningful improvement (JPRO 2022;6:114). Results Number of patients by BL UNRS score of 0-3, 4-6, or 7-10: W12 – 149, 437, 576 patients, respectively; W52 – 70, 215, 259 MIRI responders. At W12 and W52, a significantly greater proportion of MIRI-treated patients achieved clinical response, clinical remission, endoscopic remission, and symptomatic remission, regardless of UNRS score group at induction BL, for all comparisons except W52 clinical remission score 0-3 (Figure 1). In general, across clinical endpoints and regardless of BL UNRS score, MIRI treatment improved UNRS scores at W12 and W52 for a majority of patients, regardless of achievement of the clinical endpoint, although to a lesser extent when not achieved. MIRI treatment improved UNRS scores at W12 and W52 to a greater extent than PBO treatment regardless of achievement of clinical endpoint (Table 1; clinical remission data shown). Regardless of BL UNRS score, individual-point score shift data (not shown) illustrated that score shifts generally were distributed across lower scores at W12 and W52 than BL. This is relevant since Dubinsky and colleagues (JPRO 2022;6:31) demonstrated that a UNRS 1-2-point change in score can be important to a patient. Conclusion Regardless of BL bowel urgency severity based on UNRS score, MIRI is efficacious in achieving symptomatic, endoscopic, and clinical endpoints in UC patients. MIRI improves bowel urgency severity vs PBO even if clinical endpoints are not achieved. Observing shifts in UNRS scores along the UNRS scale, regardless of starting point, may aid in understanding a patient’s efficacy outcomes. These results support MIRI’s efficacy in bowel urgency and the clinical relevance of bowel urgency severity assessment over time.