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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.
- anti-tnf
- dmards (biologic)
- DAS28
- rheumatoid arthritis
- treatment
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Footnotes
Handling editor Josef S Smolen
Contributors PCT was the co-ordinating investigator. SG, PCT, IBM, GS, RL and MILW contributed to study conduct and/or data collection. All authors analysed and/or interpreted the data. All authors collaborated in the drafting and critical revision of the manuscript, with the support of a professional medical writer funded by UCB Pharma. All authors approved the final version of the manuscript and vouch for the accuracy of the analyses and the fidelity of the study to the protocol.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests SG is an employee at UCB Pharma and reports a patent pending. PCT reports grants and consultancy for UCB Pharma and Janssen, grants from Lilly and Celgene, and consultancy for AbbVie, Biogen and Novartis. IBM reports grants from AstraZeneca, Compugen and Roche, consultancy and grants from UCB Pharma, Novartis and Celgene, honoraria from UCB Pharma, grants and honoraria from BMS and Janssen, and consultancy from AbbVie, Galvani, Lilly and Pfizer. GS reports personal fees from AbbVie and Pfizer, grants and consultancy for UCB Pharma, and grants and personal fees from Celgene, Novartis, Lilly, BMS and Chugai. RL reports honoraria from UCB Pharma, Novartis, AbbVie and Pfizer, and grants and honoraria from Lilly, Janssen and BMS. DB is an employee at UCB Pharma. LI is an employee at UCB Pharma. FS is an employee at UCB Pharma and has a patent pending. MILW is an employee at UCB Pharma. SS is an employee at UCB Pharma.
Patient consent for publication Obtained.
Ethics approval Independent institutional review board approvals were obtained.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Underlying data from this manuscript may be requested by qualified researchers 6 months after product approval in the USA and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymised IPD and redacted study documents which may include raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.clinicalstudydatarequest.com and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password-protected portal.