Mirikizumab Analysis Shows Relation of Biomarkers to Mucosal Healing, Improvement

A poster presentation from the United European Gastroenterology Week meeting provided insights into the relationship of fecal calprotectin (fCal) and C-reactive protein (CRP) biomarker levels and histologic and endoscopic improvement among patients with ulcerative colitis.

The presentation was published in the Journal of Crohn’s & Colitis.

The researchers conducted an analysis of the Phase 3, randomized, double-blind, placebo-controlled LUCENT induction and maintenance trials of mirikizumab, an interleukin-23/p19 inhibitor.

“Given the importance of understanding treat-to-target strategies, the relationship between improved histologic and endoscopic endpoints and improvement of the inflammatory biomarkers faecal calprotectin (fCal) and C-reactive protein (CRP) was studied,” the authors stated.

This analysis focused on 868 patients treated with intravenous mirikizumab every 4 weeks during the induction study. At week 12, 365 induction responders rerandomized to receive subcutaneous mirikizumab every 4 weeks until week 52. “The relationship between achieving histologic-endoscopic mucosal improvement (HEMI), histologic-endoscopic mucosal remission (HEMR), and improvement of fCal (≤250µg/g) and CRP (≤6mg/L) levels at W12 and W52 was explored using Fisher’s exact tests,” the researchers explained.

At week 12, more patients treated with mirikizumab who had achieved HEMI had normalized fCal (76.2%) and CRP values (88.5%), compared to patients who did not achieve HEMI (21.8% normalized fCal and 72.7% normalized CRP). A higher proportion of patients who achieved HEMR also had normalized fCal and CRP values (79.3% and 89.6%), compared to those who did not achieve HEMR (24.3% and 73.3.)

These higher rates of fCal and CRP normalization were also seen during the maintenance period. Among the induction responders who had been rerandomized to the extension study, a  significantly higher percentage who had achieved HEMI had normalized fCal (74.1%) and CRP values (87.9%). Among patients not achieving HEMI 32.5% showed normalized fCal and 61.3% had normalized CRP. A higher proportion of patients achieving HEMR also had normalized fCal and CRP values (76.6% and 88.0%), versus patients not achieving HEMR (33.8% and 63.3%) respectively.

“At both W12 and W52, patients treated with miri who achieved HEMI or HEMR showed statistically significant improvements in fCal and CRP levels. This suggests that CRP and fCal may be useful markers of histology and endoscopy outcomes after induction and maintenance with miri,” the authors concluded.

—Rebecca Mashaw

Reference:

Panaccione R, Sapin C, Chan-Diehl FW, et al. DOP90 The association of endoscopic and histologic endpoints with faecal calprotectin and C-reactive protein in patients with moderately to severely active ulcerative colitis treated with mirikizumab. J Crohns Colitis. 2023;(17)1:i167–i169. https://doi.org/10.1093/ecco-jcc/jjac190.0130