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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
  1. Stanley B Cohen1,
  2. Alberto Alonso-Ruiz2,
  3. Piotr A Klimiuk3,
  4. Eric C Lee4,
  5. Nuala Peter5,
  6. Ivo Sonderegger5,
  7. Deepak Assudani5
  1. 1 Metroplex Clinical Research Center, Dallas, Texas, USA
  2. 2 Hospital de Cruces, Barakaldo, Spain
  3. 3 Medical University of Bialystok, Bialystok, Poland
  4. 4 Inland Rheumatology, Upland, California, USA
  5. 5 Boehringer Ingelheim, Ingelheim am Rhein, Germany
  1. Correspondence to Professor Stanley B Cohen, Metroplex Clinical Research Center, Dallas, TX 75231, USA; Scohen{at}


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.

  • rheumatoid arthritis
  • anti-tnf
  • autoimmune diseases
  • dmards (biologic)
  • treatment

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  • Handling editor Tore K Kvien

  • Contributors SBC and DA were involved in the acquisition, analysis or interpretation of the data. All authors were involved in the critical revision of the manuscript, approval to submit and in agreement to be accountable.

  • Funding Boehringer Ingelheim provided the funding and was responsible for the conduct of this study.

  • Competing interests SBC and ECL received funding from Boehringer Ingelheim, study sponsor, as principal investigators of this study. AA-R and PAK have no competing interests to declare. NP, IS and DA are (or were) employees of Boehringer Ingelheim, study sponsor.

  • Patient consent Obtained.

  • Ethics approval The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the institutional review boards of all participating centres. All patients provided written informed consent.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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