Search in the Abstract Database

Abstracts Search 2019

OP38 Maintenance treatment with mirikizumab, a p19-directed IL-23 antibody: 52-week results in patients with moderately-to-severely active ulcerative colitis

G. Geert. R. D’Haens*1, W. J. Sandborn2, M. Ferrante3, B. R. Bhandari4, E. Berliba5, T. Hibi6, J. Tuttle7, J. B. Canavan8, S. Friedrich8, M. Durante8, V. Arora8, B. Feagan9

1Amsterdam University Medical Centers, Amsterdam, The Netherlands, 2University California San Diego, La Jolla, California, USA, 3UZ Leuven, KU Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium, 4Delta Research Partners, LLC, Bastrop, LA, USA, 5Nicolae Testemițanu State University of Medicine and Pharmacy, Chisinau, Moldova, Republic of, 6Kitasato Institute Hospital Center for Advanced IBD Research and Treatment, Minato-ku, Tokyo, Japan, 7Eli Lilly and Company, Lilly Biotechnology Center, San Diego, California, USA, 8Eli Lilly and Company, Indianapolis, Indiana, USA, 9Western University, Robarts Clinical Trials Inc., London, Ontario, Canada

Background

Interleukin (IL)-23 is a critical cytokine in inflammatory bowel disease pathogenesis. Mirikizumab (miri), a p19-directed IL-23 antibody, demonstrated efficacy and was well-tolerated during 12 weeks of induction treatment in a Phase 2 randomised clinical trial (AMAC, NCT02589665).1 Maintenance results through Week 52 from this trial are reported.

Methods

Patients (Mayo score 6–12 with a minimum endoscopic subscore [ES] ≥2) were randomised 1:1:1:1 to receive intravenous (IV) placebo (N = 63), miri 50 mg (N = 63) or 200 mg (N = 62) with possibility of exposure-based (EB) dose increases, or fixed miri 600 mg (N = 61) every 4 weeks (Q4W), with efficacy assessment at Week 12. Patients who achieved a clinical response to miri at Week 12 were re-randomised 1:1 into a double-blind maintenance period to receive miri 200 mg subcutaneously (SC) Q4W (N = 47) or every 12 weeks (Q12W; N = 46), and were treated through Week 52. See Table 1 for definitions of secondary and exploratory outcomes. Missing data were imputed as nonresponse.

Abstract OP038 – Table 1.

Results

Baseline (BL) characteristics of patients who entered the maintenance period were similar between groups. At BL, 52.7% had previously received a biologic. At Week 52, 46.8% (Q4W) and 37.0% (Q12W) were in clinical remission. Additionally, 80.9% (Q4W) and 76.1% (Q12W) had clinical response, and 57.4% (Q4W) and 47.8% (Q12W) had an ES = 0/1. Among those in clinical remission at Week 12, 61.1% (Q4W) and 38.5% (Q12W) remained in clinical remission at Week 52. Among those in clinical response (but not remission) at Week 12, 37.9% (Q4W) and 36.4% (Q12W) achieved clinical remission at Week 52. Symptomatic scores throughout the maintenance period are shown in Figure 1. During the maintenance period, 1 patient discontinued study due to an adverse event (AE), and similar frequencies of treatment-emergent AEs and serious AEs were reported across both treatment groups. Additional demographic, BL disease characteristics, and outcome data are reported in Table 1.

Abstract OP038 – Figure 1

Conclusion

Miri demonstrated durable efficacy (assessed by multiple measures) with no unexpected safety signals and few discontinuations due to AEs throughout the maintenance period. These are the first data demonstrating that a p19-directed IL-23 antibody may be an effective treatment as maintenance therapy in patients with moderately-to-severely active UC.