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
Panaccione, R.(1)*;Sapin, C.(2);Chan-Diehl, F.W.(3);Moses, R.E.(3);Siegmund, B.(4);Walsh, A.(5);Kobayashi, T.(6);Parambir, D.S.(7);Travis, S.(8);
(1)University of Calgary, Faculty of Medicine at the Cumming School of Medicine, Calgary, Canada;(2)Eli Lilly France, Rheumatology & Gastroenterology – Real World & Access Analytics RWA² Global Statistical Sciences & Advanced Analytics, Neuilly sur Seine, France;(3)Eli Lilly and Company, Gastroenterology, Indianapolis, United States;(4)Universitätsmedizin Berlin, Medizinische Klinik für Gastroenterologie- Infektiologie- Rheumatologie Charité, Berlin, Germany;(5)Nuffield Health- The Manor Hospital, Translational Gastroenterology Unit, Oxford, United Kingdom;(6)Kitasato University -Kitasato Institute Hospital, Gastroenterology, Tokyo, Japan;(7)Feinberg School of Medicine Northwestern University, Gastroenterology and Hepatology, Chicago, United States;(8)Oxford University, Nuffield Department of Medicine, Oxford, United Kingdom;
Background
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, randomised, double-blind, placebo-controlled trials (LUCENT-1 NCT03518086; LUCENT-2 NCT03524092).1 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 within miri-treated patients enrolled in the programme.
Methods
This analysis focused on miri-treated patients (n=868) from the induction study receiving intravenous (IV) every 4 weeks (Q4W) until week (W)12 and miri induction responders at week W12, who were rerandomised for the maintenance period, receiving subcutaneous miri (n=365) Q4W up to W52. The relationship between achieving histologic-endoscopic mucosal improvement (HEMI), histologic-endoscopic mucosal remission (HEMR) (definitions in Tables) and improvement of fCal (≤250µg/g) and CRP (≤6mg/L) levels at W12 and W52 was explored using Fisher’s exact tests.
Results
At W12, a significantly higher percentage of miri-treated patients achieving HEMI (n=235/868) had normalised fCal and CRP values (76.2% and 88.5%), compared to miri-treated patients who did not achieve HEMI (n=633/868) (21.8% and 72.7%, both p<0.001; Table 1). Similarly, a higher proportion of patients achieving HEMR (n=193/868) had normalised fCal and CRP values (79.3% and 89.6%), compared to those who did not achieve HEMR (n=675/868) (24.3% and 73.3%, both p<0.001; Table 1).
At W52, a significantly higher percentage of the miri induction responder patients rerandomised to miri achieving HEMI (174/365) had normalised fCal and CRP values (74.1% and 87.9%), compared to patients not achieving HEMI (191/365) (32.5% and 61.3%; both p<0.001). Similarly, at W52, a higher proportion of patients achieving HEMR (n=158/365) had normalised fCal and CRP values (76.6% and 88.0%), versus patients not achieving HEMR (n=207/365) (33.8% and 63.3%; both p<0.001, Table 2).
Conclusion
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.
1.Magro et al., MP245 Efficacy of mirikizumab in resolving active histologic inflammation in Ulcerative Colitis in Lucent-1 induction and Lucent-2 maintenance trials (2022), UEG Week Moderated Posters. United European Gastroenterol J, 10: 185-472.
