Abstrakt
Background: Mirikizumab, an anti-IL-23p19 antibody, demonstrated robust efficacy in improving clinical and endoscopic endpoints with an acceptable safety profile for the treatment of moderately-to severely- active Crohn’s disease (CD) in the phase 3 VIVID-1 study 1, a double-blind, placebo-controlled, active comparator study, which has been reported previously. Here we assess the impact of mirikizumab on extra-intestinal manifestations (EIMs) in patients with CD and evaluate the long-term efficacy of mirikizumab on clinical remission and endoscopic response in patients with EIMs at baseline.
Methods: Patients randomized to receive mirikizumab (N=579) or placebo (N=199) in the VIVID-1 study were included. Among patients with at least 1 EIM at baseline, we evaluated EIM resolution, clinical remission, and endoscopic response at week (W) 52. Onset of new EIMs was assessed among patients with no EIMs at baseline. Prespecified analyses included EIM resolution and onset of new EIMs, while post hoc analyses included clinical remission and endoscopic response among patients with EIMs at baseline. Categorical endpoints were analysed using the Cochran–Mantel–Haenszel test, with missing values imputed by non-responder imputation.
Results: Of 778 patients in the mirikizumab and placebo arms of VIVID-1, 173 (22.2%) had ≥1 EIM at baseline, primarily arthritis or arthralgia. Baseline demographics and disease characteristics were similar between patients with EIMs at baseline and those in the overall population, except for a numerically higher proportion of female patients with EIMs at baseline (Table 1). At W12, a numerically higher proportion of mirikizumab-treated versus placebo-treated patients showed EIM resolution (46.2% vs 31.7%; P=0.113). Through W52, the EIM resolution rate with mirikizumab improved to 56.8%. The proportion of patients who achieved both clinical response by Patient Reported Outcome at W12 and EIM resolution at W52 was significantly higher for mirikizumab compared to placebo (43.2% vs 14.6%; P<0.0001)(Fig. 1). In addition, among patients with EIMs at baseline, higher proportions of mirikizumab-treated patients than placebo-treated patients achieved (1) clinical response at W12 and clinical remission at W52 (39.4% vs 19.5%; P<0.024) and (2) clinical response at W12 and endoscopic remission at W52 (36.4% vs 4.9%; P=0.0002). The rate of new-onset EIMs at W52 was low among all patients treated with mirikizumab or placebo (1.8% vs 1.9%; P=0.847).
Conclusion: Treatment with mirikizumab led to higher rates of EIM resolution at W52 compared to placebo. Response rates for clinical and endoscopic outcomes were similar between patients with EIMs at baseline and the overall population in VIVID-1.1
References:
1. Ferrante, et al., (in press, 2024) Efficacy and safety of mirikizumab in patients with moderately-to-severely active Crohn’s disease: a phase 3, multicentre, randomised, double-blind, placebo-controlled and active-controlled, treat-through study
Table 1. Baseline demographics, disease characteristics, and baseline extraintestinal manifestations
Patients With ≥1 EIM (N=173) Overall Population (N=778)
Female, n (%) 107 (61.8) 328 (42.2)
Age (years), mean (SD) 38.9 (14.0) 36.1 (13.1)
BMI (kg/m2), mean (SD) 24.7 (5.9) 23.4 (5.5)
Duration of CD (years), mean (SD) 9.1 (9.0) 7.5 (8.0)
CDAI score, mean (SD) 335.4 (88.4) 322.0 (85.9)
SES-CD score, mean (SD) 13.1 (6.7) 13.4 (6.4)
Disease location, n (%)
Ileal 23 (13.3%) 84 (10.8%)
Colonic 68 (39.3%) 302 (38.8%)
Ileal-colonic 82 (47.4%) 392 (50.4%)
C-reactive protein (mg/L),
median (Q1, Q3) 6.5 (2.7, 21.4) 8.1 (2.9, 23.4)
Faecal calprotectin (µg/g),
median (Q1, Q3) 944.0 (312.5, 1773.5) 1290.5 (435.0, 2547.0)
Prior biologic treatment failure, n (%)a 86, (49.7%) 378 (48.6%)
Prior anti-TNF treatment failure, n (%)a 77 (44.5%) 354 (45.5%)
Patients With ≥1 EIM (N= 173)
Placebo (N=41) Mirikizumab (N=132)
Arthritis/arthralgia, n(%) 39 (95.1%) 117 (88.6%)
Iritis/uveitis, n(%) 1 (2.4%) 3 (2.3%)
Erythema nodosum, pyoderma gangrenosum, aphthous stomatitis, n(%) 4 (9.8%) 17 (12.9%)
BMI, body mass index; CD, Crohn’s disease; CDAI, Crohn's Disease Activity Index; EIM, extra intestinal manifestations; Q1, first quartile; Q3, third quartile; SD, standard deviation; SES-CD, Simple Endoscopic Score for Crohn's Disease; TNF, tumour necrosis factor
aFailure was defined as prior treatment discontinuation due to loss of response, inadequate response, or intolerance to medication.
Disclosures: S. Vavricka has received consulting fees, speakers honoraria, and unrestricted research grants from: Abbott, Alfasigma, Amgen, Arenapharm, Bristol Myers Squibb, Dr. Falk Pharma, Ferring Pharmaceuticals, Gilead Sciences, iQone Healthcare, Janssen, Merck Sharp & Dohme, Permamed, Pfizer, Sanofi-Aventis, Schwabe Pharma, Takeda, Tillotts Pharma AG, UCB Pharma, and Vifor Pharma; A. Ananthakrishnan has served on scientific advisory boards for: AbbVie, Gilead Sciences, Merck Sharp & Dohme, and Takeda; and has received research support from: Pfizer; M. Long has served as a consultant for: AbbVie, Bristol Myers Squibb, Eli Lilly and Company, Pfizer, Prometheus, Takeda, and Target RWE; and has received research support from: Janssen, Pfizer, and Takeda; G. Y. Melmed has been a consultant/advisor for: AbbVie, Arena Biopharmaceuticals, Boehringer Ingelheim, BioQuest Solutions, Boomerang, Bristol Myers Squibb, Diasorin, Dieta, Eli Lilly and Company, Ferring Pharmaceuticals, Fresenius Kabi, Gilead Sciences, Iterative Health, Janssen, Johnson & Johnson, Medtronic, Oshi Health, Option Care Health, Samsung Bioepis, Shield Therapeutics, Pfizer, Prometheus Laboratories, Rippling, Shionogi, Takeda, TechLab, Verantos, and Viatris; has been a speaker for: AbbVie and Johnson & Johnson; and has stock options in: Dieta and Oshi Health; N. Narula has received advisory fees from: AbbVie, Amgen, Celltrion, Eli Lilly and Company, Ferring Pharmaceuticals, Fresenius Kabi, Innomar, Iterative Scopes, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Sandoz, and Takeda; has received speaker fees from: AbbVie, Celltrion, Eli Lilly and Company, Janssen, Merck Sharp & Dohme, Pfizer, and Takeda; and has received grants for clinical trials from AbbVie, Pfizer, and Takeda; D. T. Rubin has received grants or contracts from: Takeda; and has received consulting fees from: AbbVie, Allergan, AltruBio, American College of Gastroenterology, Arena Pharmaceuticals, Athos Therapeutics, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Corp/Syneos, Cornerstones Health, Eli Lilly and Company, Galen/Atlantica, Genentech/Roche, Gilead Sciences, GoDuRn, InDex Pharmaceuticals, Ironwood Pharmaceuticals, Iterative Scopes, Janssen, Materia Prima, Pfizer, Prometheus Biosciences, Reistone Biopharma, Takeda, and TechLab; E. Hon, H. Carlier, R. Moses, G. Yu, H. Zang and I. Vachova are current employees and shareholders of: Eli Lilly and Company; T. Kucharzik has received consulting fees and honoraria from: AbbVie, Amgen, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly and Company, Hospira, Ferring Pharmaceuticals, Dr. Falk Pharma, Galapagos NV, Gilead Sciences, Janssen, Merck Sharp & Dohme, Mundipharma, Novartis, Takeda, and Pfizer.
Funded by Eli Lilly and Company.
Previously presented at the European Crohn's and Colitis Organisation (ECCO), Berlin, Germany; 19-22 February 2025.
