THU0182 A comparative clinical study of pf-06410293, a candidate adalimumab biosimilar, and reference adalimumab for the treatment of active rheumatoid arthritis
Authors: R. Alten, R.M. Fleischmann, M. Pileckyte, S.Y. Hua, C. Cronenberger, A.E. Bock, K.L. Sewell
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> To confirm the efficacy, safety and immunogenicity of biosimilars, a comparative clinical study is typically required. <h3>Objectives</h3> 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-naïve patients (pts) with active rheumatoid arthritis (RA) despite methotrexate (MTX; 10–25 mg/wk). <h3>Methods</h3> 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) &lt;2.6, and ACR/EULAR remission. QuantiFERON-TB testing was performed at Screening and Wk 26. <h3>Results</h3> 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) &lt;2.6 and ACR/EULAR remission were similar between arms at each visit. Incidence of treatment–emergent adverse events (AEs) was 48.1% vs 47.8%, serious AEs were 4.0% vs 4.3% (with a fatal myocardial infarction in the ADA–EU arm) and serious infections were 0.7% vs 1.3% for PF–06410293 and ADA–EU, respectively. Injection site reactions occurred at 1.7% vs 2.0%, hypersensitivity events at 4.4% vs 8.4%, pneumonia at 0.7% vs 2.0%, and latent tuberculosis (based on specialist consultation for Wk 26 QuantiFERON-TB +) at 1.7% vs 0.3% for PF–06410293 and ADA–EU, respectively. Post–dose anti–drug antibody rates to Wk 26 were 44.4% (PF–06410293) and 50.5% (ADA–EU). <h3>Conclusions</h3> 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. <h3>Disclosure of Interest</h3> 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