Fecal Calprotectin and C-Reactive Protein Association With Histologic and Endoscopic Endpoints in Mirikizumab-Treated Patients With Ulcerative Colitis.

Background: Fecal calprotectin (FC) and C-reactive protein (CRP) are noninvasive biomarkers used in ulcerative colitis (UC) clinical trials; however, thresholds defined as "normal" in trials may be higher than "normal" thresholds typically used in clinical practice. We assessed the relationship between FC and CRP improvement in the "normal" range across different cutoff thresholds for patients with moderately to severely active UC treated with mirikizumab.

Methods: Patients achieving clinical response to mirikizumab in LUCENT-1 (Weeks 0-12) proceeded to LUCENT-2 (Weeks 12-52 [52 weeks of continuous mirikizumab]). Associations between FC and CRP levels at multiple thresholds and histologic-endoscopic mucosal improvement (HEMI) and histologic-endoscopic mucosal remission (HEMR) at Weeks 12 and 52 were assessed by Fisher's exact test. Least squares means of FC and CRP changes from baseline at Weeks 12 and 52 were calculated using analysis of covariance with HEMI or HEMR status as factors and baseline FC or CRP values as covariates.

Results: At Weeks 12 and 52, greater proportions of patients with FC thresholds of ≤250, ≤150, ≤100, and ≤50 µg/g, and CRP thresholds of ≤6 and ≤5 mg/L, achieved HEMI and HEMR compared with those not achieving HEMI and HEMR. Changes from baseline in FC and CRP at Week 12 and FC at Week 52 were greater in patients who achieved HEMI and HEMR compared with those not achieving these endpoints.

Conclusions: These results show that FC and CRP analyses may contribute to a noninvasive monitoring strategy in clinical practice.ClinicalTrials.gov numbers: NCT03518086, NCT03524092.