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

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.

Keywords: DAS28; anti-tnf; dmards (biologic); rheumatoid arthritis; treatment.

Conflict of interest statement

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.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Study design. DAS28(CRP), Disease Activity Score 28-joint count (C-reactive protein); Q2W, once every 2 weeks.

Figure 2

Patient disposition. *Inadequate response was defined as Disease Activity Score 28-joint count (C-reactive protein) >3.2. IR, inadequate response.

Figure 3

DAS28(CRP) remission by visit (A), percentage of ACR20 (B), ACR50 (C) and ACR70 (D) responders based on Week 8 in the certolizumab pegol-IR plus bimekizumab and certolizumab pegol-IR plus placebo groups. At Week 20, the add-on therapy (bimekizumab or placebo) was withdrawn; certolizumab pegol continued until Week 32. All patients continued certolizumab pegol therapy until Week 32, after which their treatment was determined by their clinician outside of the study protocol. There was a final follow-up visit at Week 44. See online supplementary table S5 for actual data. Error bars represent Wilson’s 95% CI. ACR20, ACR50, ACR70, American College of Rheumatology 20%, 50% and 70% improvement criteria; DAS28(CRP), Disease Activity Score 28-joint count (C-reactive protein).