B0351 - The Effect of Mirikizumab on Fecal Calprotectin and C-Reactive Protein in Phase 3 Studies of Patients With Moderately-to-Severely Active Ulcerative Colitis

Introduction: This study explores the effect of mirikizumab (miri) on inflammatory biomarkers fecal calprotectin (FC) and C-reactive protein (CRP) in patients with moderately-to-severely active ulcerative colitis (UC).

Methods: In LUCENT-1 (NCT03518086), 1162 patients were randomized 3:1 to receive intravenous miri 300 mg or placebo (PBO) every 4 weeks for 12 weeks. Patients (N=544) who achieved clinical response with miri at Week (W) 12 were re-randomized 2:1 in LUCENT-2 (NCT03524092) to receive blinded miri 200 mg or PBO subcutaneously every 4 weeks through W40 (52 weeks continuous therapy). Treatment comparison of change from baseline in FC and CRP levels were made using ANCOVA analysis. Comparison of proportion of patients achieving FC ≤250 μg/g used a Cochran–Mantel Haenszel test treating missing data as nonresponse.

Results: At baseline, the median FC was 1556.0 µg/g in the miri group and 1465.0 µg/g in the PBO group (Table); the proportion of patients with FC >250 µg/g were similar between treatment groups (miri: 90.4%; PBO: 88.9%). At both W4 and W12 of LUCENT-1, miri-treated patients showed greater reduction in FC from baseline compared to PBO (p< .001). Among patients with baseline FC level >250 µg/g, a greater proportion of miri-treated patients achieved an FC level of ≤250 µg/g compared to PBO (34.3% vs 20.1%; adjusted risk difference: 14.6%; 95% confidence interval [CI]: 8.3%–20.9%; p< .001) at W12. For those who continued with maintenance therapy in LUCENT-2, at W40, miri-treated patients sustained greater FC reduction from baseline compared to PBO (p< .001). A greater proportion of miri-treated patients with induction baseline FC >250 µg/g achieved FC level of ≤250 µg/g compared to PBO (50.7% vs 19.3%; adjusted risk difference: 29.1%; 95% CI: 20.5%–37.7%; p< .001) at W40. At baseline, the median CRP was 4.0 mg/L in the miri group and 4.3 mg/L in the PBO group (Table). At W12, patients in the miri group showed greater reduction in CRP from baseline compared to PBO (p< .001). Among those who continued in LUCENT-2, at W40, miri-treated patients sustained greater reduction in CRP from baseline compared to PBO (p< .001).

Discussion: Patients treated with miri in both induction and maintenance studies were more likely to achieve an FC ≤ 250 µg/g and showed significantly greater reductions from baseline in FC and CRP when compared to PBO.