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, 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.
Aims & 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). 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). 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).
Relationship between mirikizumab treated patients achieving HEMI and HEMR at end of induction (W12) and normalised faecal calprotectin and C-reactive protein values
| Relationship between mirikizumab responder patients rerandomised to mirikizumab achieving HEMI and HEMR at end of maintenance (W52) and normalised faecal calprotectin and C-reactive protein values
|
| Mirikizumab treated patients (N=868) | Mirikizumab induction responder patients rerandomised to mirikizumab (n=365)
|
End of induction-
Week 12
| Patients achieving HEMI (n=235)
| Patients not achieving HEMI (n=633)
| p-value
| End of maintenance- Week 52 | Patients achieving HEMI (n=174)
| Patients not achieving HEMI (n=191)
| p-value
|
| % fCal ≤ 250µg/g | 179 (76.2%)
| 138 (21.8%)
| <0.001
| % fCal≤250µg/g
| 129 (74.1%)
| 62 (32.5%)
| <0.001
|
% CRP ≤ 6mg/L
| 208 (88.5%)
| 460 (72.7%) | <0.001
| % CRP≤6mg/L
| 153 (87.9%)
| 117 (61.3%)
| <0.001
|
End of induction-
Week 12
| Patients achieving HEMR (n=193)
| Patients not achieving HEMR (n=675)
| p-value
| End of maintenance-Week 52
| Patients achieving HEMR (n=158)
| Patients not achieving HEMR (n=207)
| p-value
|
% fCal ≤ 250µg/g
| 153 (79.3%)
| 164 (24.3%)
| <0.001
| % fCal≤250µg/g
| 121 (76.6%)
| 70 (33.8%)
| <0.001 |
% CRP ≤ 6mg/L
| 173 (89.6%)
| 495 (73.3%)
| <0.001
| % CRP≤6mg/L
| 139 (88.0%)
| 131 (63.3%)
| <0.001
|
| Abbreviations: CRP=C-reactive protein; fCal=faecal calprotectin; HEMI=Histologic-endoscopic mucosal improvement defined as Mayo Endoscopic Subscore (ES)=0 or 1 (excluding friability) and Geboes≤3.1; HEMR Histologic-endoscopic mucosal remission defined as ES=0 or 1 (excluding friability) + Geboes≤2b; N=patient population; n=patient subpopulation; W=week |
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.
References
- 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.
Disclosure
R. Panaccione has received speaker fees and/or served as a consultant and/or advisory board member for: Abbott, AbbVie, Alimentiv, Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Cosmo Pharmaceuticals, Eisai, Elan Pharma, Eli Lilly and Company, Ferring Pharmaceuticals, Galapagos NV, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Mylan, Oppilan Pharma, Pandion Therapeutics, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda, Theravance Biopharma and UCB Pharma; and has received research and/or educational support from: AbbVie, Ferring Pharmaceuticals, Janssen, Pfizer and Takeda; C. Sapin, F. Chan-Diehl and R. Moses are employees and shareholders of: Eli Lilly and Company;
B. Siegmund has served as a consultant and/or speaker for: AbbVie, Arena Pharmaceuticals, Bristol Myers Squibb, Boehringer Ingelheim, CED Service GmbH, Celgene, Dr Falk Pharma, Eli Lilly and Company, Ferring Pharmaceuticals, Galapagos NV, Janssen, Novartis, Pfizer, Prometheus Therapeutics and Takeda;
A. Walsh has received grant and/or research support from: AbbVie and Pfizer; and has received consultancy fees from: AbbVie, Eli Lilly and Company, Novartis and UCB Pharma;
T. Kobayashi has served as a speaker, consultant and advisory board member for: AbbVie, Ajinomoto Bio-Pharma, Alfresa Pharma, Asahi Kasei Pharma, Astellas, Bristol Myers Squibb, Celltrion, Covidien, EA Pharma, Eisai, Eli Lilly and Company, Ferring Pharmaceuticals, Galapagos NV, Gilead Sciences, Janssen, JIMRO, Kyorin, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Takeda, Thermo Fisher Scientific and Zeria Pharmaceutical; and has received research funding from: AbbVie, ActivAid, Alfresa Pharma, Asahi Kasei Pharma, EA Pharma, Google, JMDC, Kyorin, Mochida Pharmaceutical, Nippon Kayaku, Otsuka, Sekisui Medical, Thermo Fisher Scientific and Zeria Pharmaceutical;
P. S. Dulai has served as a consultant for: AbbVie, Abivax, Addiso, Bristol Myers Squibb, Eli Lilly and Company, Janssen, Pfizer, Precidiag, Prometheus and Takeda;
S. Travis has received grants from: AbbVie, BUHLMANN Diagnostics, ECCO, Eli Lilly and Company, Ferring Pharmaceuticals, International Organization for the Study of Inflammatory Bowel Disease, Janssen, Merck Sharp & Dohme, Norman Collision Foundation, Pfizer, Procter & Gamble, Schering-Plough, Takeda, UCB Pharma, Vifor Pharma and Warner Chilcott; and reports other disclosures from: Abacus Pharma, AbbVie, Actial Farmaceutica, ai4gi, Alcimed, Allergan, Amgen, Aptel, Arena Pharmaceuticals, Asahi Kasei Pharma, Aspen Pharmacare, Astellas, AstraZeneca, Atlantic Pharmaceuticals, Barco, Biocare Medical, Biogen, BL Pharma, Boehringer Ingelheim, Bristol Myers Squibb, BUHLMANN Diagnostics, Calcico Therapeutics, Celgene, Cellerix, Cerimon Pharmaceuticals, ChemoCentryx, Chiesi, Cisbio, Comcast, Coronado Biosciences, Cosmo Pharmaceuticals, Dr Falk Pharma, Ducentis BioTherapeutics, Dynavax Technologies, Elan, Eli Lilly and Company, Enterome, Equillium, Ferring Pharmaceuticals, Galapagos NV, Genentech/Roche, Genzyme, Gilead Sciences, GlaxoSmithKline, Glenmark Pharmaceuticals, Grünenthal, GW Pharmaceuticals, Immunocore, Indigo Biosciences, Janssen, Lexicon Pharmaceuticals, Medarex, MedTrix, Merck, Merrimack Pharmaceuticals, Mestag Therapeutics, Millennium Pharmaceuticals, Neovacs, Novartis, Novo Nordisk, NPS Pharmaceuticals/Nycomed, Ocera Therapeutics, OPTIMA Pharma, Origin Pharma, Otsuka, Procter & Gamble, Palau Pharma, Pentax Medical, Pfizer, PharmaVentures, Phesi, Phillips Pharma Group, Pronota, Proximagen, Resolute, Robarts Clinical Trials, Sandoz, Santarus, Satisfai Health, Sensyne Health, Shire, Sigmoid Pharma, Sorriso Pharmaceuticals, Souffinez, SynDermix, Synthon, Takeda, Theravance Biopharma, TiGenix, Tillotts Pharma AG, Topivert, Trino Therapeutics with Wellcome Trust, TxCell, UCB Pharma, Vertex Pharma, VHsquared, Vifor Pharma, Warner Chilcott and Zeria Pharmaceutical