THU0182 A comparative clinical study of pf-06410293, a candidate adalimumab biosimilar, and reference adalimumab for the treatment of active rheumatoid arthritis

Background To confirm the efficacy, safety and immunogenicity of biosimilars, a comparative clinical study is typically required. Objectives This double-blind, randomised, 78 week (wk) study compared the efficacy, safety and immunogenicity of PF–06410293, a candidate adalimumab biosimilar, with reference adalimumab sourced from the EU (ADA–EU), in biologic-naive patients (pts) with active rheumatoid arthritis (RA) despite methotrexate (MTX; 10–25 mg/wk). Methods Pts with active RA (n=597) were stratified by region and randomised (1:1) to PF–06410293 or ADA-EU (40 mg subcutaneous injection every 2 wks), with continued MTX. The primary endpoint was American College of Rheumatology 20% improvement (ACR20) at Wk 12. Therapeutic equivalence was concluded if the 2–sided 95% confidence interval (CI) for the difference in Wk 12 ACR20 between arms was within the symmetric equivalence margin of ±14%. Additionally, a 2–sided 90% CI was requested by the US Food and Drug Administration, using the asymmetric equivalence margin of −12% to +15%. Secondary efficacy endpoints to Wk 26 included ACR20/50/70, change from baseline Disease Activity Score in 28 joints [DAS28(CRP)], European League Against Rheumatism (EULAR) response, achievement of DAS28(CRP) Results Pts (78.7% female, 81.6% seropositive) had a mean age of 52.5 years, and mean RA duration of 6.8 years. Mean baseline DAS28(CRP) was 5.9 (PF–06410293) and 6.1 (ADA–EU). The observed Wk 12 ACR20 was 68.7% (PF–06410293) and 72.7% (ADA–EU) in the intent-to-treat population (figure 1). Using non-responder imputation (n=19; 3.2%), the treatment difference in Wk 12 ACR20 was −2.98%, and the corresponding CIs [95% CI (−10.38%,+4.44%); 90% CI (−9.25%,+3.28%)] were entirely contained within both equivalence margins (symmetric and asymmetric). The ACR20 difference ranged from −3.98% to +5.50% (Wks 2–26). Mean DAS28(CRP) change from baseline at Wk 26 was −2.7 and −2.8 in the PF–06410293 and ADA–EU arms, respectively. ACR50/70, EULAR response, DAS28(CRP) Conclusions The efficacy, safety and immunogenicity of PF–06410293 and ADA–EU were similar up to Wk 26 in pts with active RA on MTX. At Wk 26, pts on ADA-EU were blindly re-randomised (1:1) to continue ADA-EU or transition to PF-06410293 for ongoing treatment in the study. Disclosure of Interest R. Alten Speakers bureau: Pfizer, R. Fleischmann Grant/research support from: Pfizer and AbbVie, Consultant for: Pfizer and AbbVie, M. Pileckyte: None declared, S. Hua Shareholder of: Pfizer, C. Cronenberger Shareholder of: Pfizer, Employee of: Pfizer, A. Bock Shareholder of: Pfizer, Employee of: Pfizer, K. Sewell Shareholder of: Pfizer, Employee of: Pfizer