Efficacy, Safety, and Immunogenicity of Biosimilar Etanercept (Enerceptan) Versus Its Original Form in Combination With Methotrexate in Patients With Rheumatoid Arthritis: A Randomized, Multicenter, Evaluator-Blinded, Noninferiority Study

J Clin Rheumatol. 2021 Sep 1;27(6S):S173-S179. doi: 10.1097/RHU.0000000000001616.

Abstract

Background: Enerceptan (EtaBS) has been developed as a proposed biosimilar of etanercept.

Methods: This randomized, multicenter, evaluator-blinded, noninferiority study conducted in Argentina included adults with active, moderate, and severe rheumatoid arthritis with inadequate response to methotrexate. Subjects were randomly assigned to 32 weeks treatment with EtaBS (n = 99) or etanercept (n = 51) at a weekly 50-mg dose administered subcutaneously. Patients were categorized according to prior use of biologic disease-modifying antirheumatic drugs and concomitant use of steroids. The primary efficacy endpoint was ACR20 response rate at week 32. Safety, immunogenicity, and steady-state concentration of both drugs were evaluated. The noninferiority margin for ACR20 was estimated at 12%.

Results: In the per-protocol population, 85 subjects (92.4%) treated with EtaBS and 44 subjects (93.6%) treated with etanercept achieved ACR20 (difference, -1.2%; 95% confidence interval, -10.1% to 7.6%). Frequent adverse drug reactions occurred in 34.3% and 38% of subjects treated with EtaBS and etanercept, respectively. The most common reaction was upper respiratory tract infection. Six and 3 serious adverse events occurred in 4 and 3 subjects treated with EtaBS and etanercept, respectively. Injection site reactions occurred in 67.7% and 66.0% of subjects treated with EtaBS and etanercept, respectively. Two subjects treated with EtaBS and 1 subject treated with etanercept developed antibodies by week 32.

Conclusions: Efficacy outcomes for EtaBS were noninferior to original etanercept in patients with moderate-to-severe rheumatoid arthritis with inadequate response to methotrexate. Safety and immunogenicity results were comparable between the two. This study is a major step toward improving access to biologics in Latin America.

Trial registration: ClinicalTrials.gov NCT03332719.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antirheumatic Agents* / adverse effects
  • Arthritis, Rheumatoid* / diagnosis
  • Arthritis, Rheumatoid* / drug therapy
  • Biosimilar Pharmaceuticals* / adverse effects
  • Double-Blind Method
  • Drug Therapy, Combination
  • Etanercept / adverse effects
  • Humans
  • Methotrexate / adverse effects
  • Treatment Outcome

Substances

  • Antirheumatic Agents
  • Biosimilar Pharmaceuticals
  • Etanercept
  • Methotrexate

Associated data

  • ClinicalTrials.gov/NCT03332719