S1335 Association of Faecal Calprotectin With Symptomatic, Endoscopic, and Clinical Remission in Patients With Moderately to Severely Active Ulcerative Colitis Treated With Mirikizumab

Introduction: Mirikizumab (miri), a p19-directed IL-23 antibody, has been shown to be effective in patients with moderately-to-severely active ulcerative colitis (UC) in Phase 3 trials (LUCENT-1 NCT03518086; LUCENT-2 NCT03524092). The relationship between symptomatic, endoscopic, and clinical remission and levels of the inflammatory biomarker faecal calprotectin (fCAL) was studied for miri-treated patients enrolled in the trials. Methods: This post hoc analysis evaluated patients treated with intravenous (IV) miri 300mg every 4 weeks (every 4 weeks) until week (W)12 in induction (n=868) followed by subcutaneous miri (n=365) every 4 weeks up to W52 (miri induction responders at W12 who were rerandomized for the maintenance period) or placebo. The improvement in fCAL at W12 and W52 between miri and placebo were compared using Cochran Mantel Haenszel, adjusting for randomization stratification factors. Missing data were imputed as nonresponse. The relationship between achieving symptomatic, endoscopic, or clinical remission (defined in Table) and fCAL levels at W4, W12 and W52 was assessed using receiver operating characteristic (ROC) approaches. Predictability was measured by area under the ROC curve (AUC), and AUC≤0.5 indicates no predictability. Optimal fCAL threshold was obtained based on Youden Index. Results: Greater proportions of miri-treated patients compared to placebo achieved fCAL≤250 ug/g at W4, W12, and W52. A total of 19.0% vs 12.5%, 34.3% vs 20.1%, 50.7% vs 19.3% patients achieved fCAL≤250 ug/g at W4, W12, and W52 miri vs placebo, respectively. Greater proportions of patients achieving symptomatic, endoscopic, and clinical remission reached the predefined threshold of fCAL≤250 ug/g or the optimum fCAL threshold obtained from the ROC (see Table footnote) in this study compared with those not achieving the endpoints (Table 1). W4 fCAL levels had 70.5% predictability for W12 endoscopic remission and 64.9% for clinical remission, but lower predictability for symptomatic remission (59.1%). W12 fCAL levels had 83.0% predictability for W12 endoscopic remission, 78.5% for clinical remission, and 67.4% for symptomatic remission. W52 fCAL levels had higher predictability for W52 endoscopic (76.6%) and clinical remission (72.7%) than for symptomatic remission (62.3%). Conclusion: These results support the use of fCAL as an early predictor of clinical outcomes and as a non-invasive biomarker for predicting clinical outcomes. Table 1. - Faecal Calprotectin Normalization at Week 12 in LUCENT-1 and Week 52 in LUCENT-2 Per Achievement of Efficacy Outcomes Symptomatic Remission Endoscopic Remission Clinical Remission Week 4 Achieving (N=360) Not Achieving (N=406) Achieving (N=290) Not Achieving (N=478) Achieving (N=193) Not Achieving (N=571) fCAL ≤ 250 ug/g 109 (30.3) 79 (19.5)╪ 122 (42.1) 65 (13.6) ╪ 77 (39.9) 110 (19.3)╪ Optimum fCAL threshold 193 (53.6) 159(39.2)╪ 158 (54.5) 106 (22.2)╪ 103 (53.4) 168 (29.4)╪ Week 12 Achieving (N=364) Not Achieving (N=398) Achieving (N=293) Not Achieving (N=472) Achieving (N=199) Not Achieving (N=562) fCAL ≤ 250 ug/g 200 (55.0) 116 (29.2)╪ 216 (73.7) 100 (21.2)╪ 151 (75.9) 164 (29.2)╪ Optimum fCAL threshold 237 (65.1) 149 (37.4)╪ 216 (73.7) 93 (19.7)╪ 151 (75.9) 157 (27.9)╪ Week 52 Achieving (N=230) Not Achieving (N=44) Achieving (N=188) Not Achieving (N=93) Achieving (N=166) Not Achieving (N=107) fCAL ≤ 250 ug/g 161 (70.0) 22 (50.0)* 151 (80.3) 38 (40.9)╪ 133 (80.1) 49 (45.8)╪ Optimum fCAL threshold 161 (70.0) 21 (47.7)* 134 (71.3) 24 (25.8)╪ 129 (77.7) 42 (39.3)╪ Abbreviations: ES=Endoscopic Subscore; fCAL=Fecal Calprotectin; RB = Rectal Bleeding; SF=Stool Frequency.Note: Data shown as n(%) unless otherwise noted. *P < 0.05 and ╪P < 0.001; P-value is from Fisher's exact test.Symptomatic remission is defined as SF = 0 or SF = 1 with a ≥ 1-point decrease from baseline, and RB = 0. Endoscopic Remission is defined as ES = 0 or 1 (excluding friability). Clinical remission is defined as SF = 0 or SF = 1 with a ≥ 1-point decrease from baseline, RB = 0, and ES = 0 or 1 (excluding friability). Optimal fCAL threshold for symptomatic remission/endoscopic remission/ and clinical remission is at ≤585/≤390/≤415 ug/g at Week 4, ≤365/≤230/≤230 ug/g at Week 12, and ≤230/≤150/≤205 ug/g at Week 52, respectively.

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