Efficacy and safety of bimekizumab as add-on therapy for rheumatoid arthritis in patients with inadequate response to certolizumab pegol: a proof-of-concept study

Glatt, S., Taylor, P. C., McInnes, I. B. , Schett, G., Landewé, R., Baeten, D., Ionescu, L., Strimenopoulou, F., Watling, M. I.L. and Shaw, S. (2019) Efficacy and safety of bimekizumab as add-on therapy for rheumatoid arthritis in patients with inadequate response to certolizumab pegol: a proof-of-concept study. Annals of the Rheumatic Diseases, 78(8), pp. 1033-1040. (doi: 10.1136/annrheumdis-2018-214943) (PMID:31177099) (PMCID:PMC6691864)

Abstract

Objective: Evaluate the efficacy and safety of dual neutralisation of interleukin (IL)-17A and IL-17F with bimekizumab, a monoclonal IgG1 antibody, in addition to certolizumab pegol (CZP) in patients with rheumatoid arthritis (RA) and inadequate response (IR) to certolizumab pegol. Methods: During this phase 2a, double-blind, proof-of-concept (PoC) study (NCT02430909), patients with moderate-to-severe RA received open-label CZP 400 mg at Weeks 0, 2 and 4, and 200 mg at Week 6. Patients with IR at Week 8 (Disease Activity Score 28-joint count C-reactive protein (DAS28(CRP))>3.2) were randomised 2:1 to CZP (200 mg every 2 weeks (Q2W)) plus bimekizumab (240 mg loading dose then 120 mg Q2W) or CZP plus placebo. The primary efficacy and safety variables were change in DAS28(CRP) between Weeks 8 and 20 and incidence of treatment-emergent adverse events (TEAEs). Results: Of 159 patients enrolled, 79 had IR at Week 8 and were randomised to CZP plus bimekizumab (n=52) or CZP plus placebo (n=27). At Week 20, there was a greater reduction in DAS28(CRP) in the CZP-IR plus bimekizumab group compared with the CZP-IR plus placebo group (99.4% posterior probability). The most frequent TEAEs were infections and infestations (CZP plus bimekizumab, 50.0% (26/52); CZP plus placebo, 22.2% (6/27)). Conclusions: PoC was confirmed based on the rapid decrease in disease activity achieved with 12 weeks of CZP plus bimekizumab. No unexpected or new safety signals were identified when neutralising IL-17A and IL-17F in patients with RA concomitantly treated with CZP, but the rate of TEAEs was higher with dual inhibition.

• Item Type: Articles
• Keywords: DAS28, anti-tnf, dmards (biologic), rheumatoid arthritis, treatment.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McInnes, Professor Iain
• Authors: Glatt, S., Taylor, P. C., McInnes, I. B., Schett, G., Landewé, R., Baeten, D., Ionescu, L., Strimenopoulou, F., Watling, M. I.L., and Shaw, S.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Research Centre: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
• Journal Name: Annals of the Rheumatic Diseases
• Publisher: BMJ Publishing Group
• ISSN: 0003-4967
• ISSN (Online): 1468-2060
• Published Online: 08 June 2019
• Copyright Holders: Copyright © 2019 The Authors
• First Published: First published in Annals of the Rheumatic Diseases 78(8):1033-1040
• Publisher Policy: Reproduced under a Creative Commons License