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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. 2020 Dec 14;Publish Ahead of Print doi:10.1097/RHU.0000000000001616.Online ahead of print.

Ingrid Strusberg 1, Eduardo Mysler, Gustavo Citera, Daniel Siri, Maria de Los Ángeles Correa, Maria Alicia Lazaro, Rodolfo Pardo Hidalgo, Alberto Spindler, Patricio Tate, Horacio Venarotti, Jorge Velasco Zamora, Ezequiel Klimovsky, Andrea Federico, Eduardo Scheines, Eliseo Gonzalez, Lucas Cordeiro, Nestor Lago

Author Information

1 From the Instituto Strusberg, Córdoba Organización Médica de Investigación Instituto de Rehabilitación Psicofísica, Buenos Aires Head of Rheumatology, CAICI Institute, Rosario Consultorios Reumatológicos Pampa CABA, Buenos Aires Head of Rheumatology, Institute IMAC SI, San Isidro CER San Juan, San Juan Centro Médico Privado de Reumatología, Tucumán OMI Centro Médico Hospital Militar Central, Atención Integral en Reumatología-AIR, Buenos Aires CER Research Institute, Articular Foundation, Quilmes QUID Quality in Drugs SRL Instituto de Rehabilitación Psicofísica Centro de Diagnóstico Molecular S.A. Gema Biotech SAU, Buenos Aires, Argentina.


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.