Similar efficacy, safety and immunogenicity of adalimumab biosimilar BI 695501 and Humira reference product in patients with moderately to severely active rheumatoid arthritis: results from the phase III randomised VOLTAIRE-RA equivalence study

Abstract

Objective: To demonstrate clinical equivalence of adalimumab biosimilar candidate BI 695501 with Humira.

Methods: Patients with active rheumatoid arthritis on stable methotrexate were randomised to BI 695501 or Humira in a double-blind, parallel-group, equivalence study. At week 24, patients were rerandomised to continue BI 695501 or Humira, or switch from Humira to BI 695501. The coprimary endpoints were the percentage of patients achieving the American College of Rheumatology 20% response criteria (ACR20) at weeks 12 and 24. Further efficacy and safety endpoints and immunogenicity were assessed up to week 58.

Results: 645 patients were randomised. At week 12, 67.0% and 61.1% (90% CI -0.9 to 12.7) of patients receiving BI 695501 (n=324) and Humira (n=321), respectively, achieved ACR20; at week 24 the corresponding values were 69.0% and 64.5% (95% CI -3.4 to 12.5). These differences were within prespecified margins (week 12: 90% CI (-12% to 15%); week 24: 95% CI (-15% to 15%)), demonstrating therapeutic bioequivalence. 593 patients were rerandomised at week 24. Up to week 48, mean change from baseline in Disease Activity Score 28-erythrocyte sedimentation rate and ACR20/ACR50/ACR70 response rates were similar across the switched (n=147), continuous BI 695501 (n=298) and continuous Humira (n=148) groups. Similar immunogenicity (antidrug antibodies (ADAs), ADA titres and neutralising antibodies) was seen between BI 695501 and Humira (to week 24) and across rerandomised groups (to week 48). Safety and tolerability profiles were similar between groups.

Conclusions: BI 695501 demonstrated similar efficacy, safety and immunogenicity to Humira; switch from Humira to BI 695501 had no impact on efficacy, safety and immunogenicity.

Trial registration number: NCT02137226, Results.

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

Figure 1

VOLTAIRE-RA study design (A) and patient disposition (B). *Patients continued with methotrexate 15–25 mg/week. Methotrexate 10–14 mg/week was permitted for patients with documented intolerance to higher doses of methotrexate. †Humira 40 mg/0.8 mL solution for subcutaneous injection. EOT, end of treatment; EOW, every other week; n, number of patients per group.

Figure 2

Week 24 results (A–C). Percentage of patients with ACR20/ACR50/ACR70 responses; bars show SEs (A). Mean DAS28-ESR; bars show SDs (B). EULAR responses (C). Week 48 results (D–F). Percentage of patients with ACR20/ACR50/ACR70 responses. Bars show SEs (D). Mean DAS28-ESR; bars show SDs (E). EULAR responses (F). ACR, American College of Rheumatology; DAS28-ESR, Disease Activity Score in 28 joints-erythrocyte sedimentation rate; EULAR, European League Against Rheumatism.

Figure 3

Week 24 results (A–C). Percentage of patients with positive ADA/nAb test (A). ADA titre (B). Drug plasma concentration by presence of ADAs (C). Week 48 results (D–F). Percentage of patients with positive ADA/nAb test (D). ADA titre (E). Drug plasma concentration by presence of ADAs (F). ADA, antidrug antibodies; n, number of patients per group; nAb, neutralising antibodies.