Abstract
BACKGROUND: Biosimilar etanercept presents itself as an innovative therapeutic opportunity for inflammatory and autoimmune diseases, however, its efficacy, safety, and immunogenicity in relation to the reference biological agent for the treatment of rheumatoid arthritis is still questioned. With this in mind, this study aimed to verify the efficacy, safety, and immunogenicity of the use of the biosimilar etanercept in relation to the reference biologic in patients over 18 years of age with rheumatoid arthritis. METHODS: A systematic review with meta-analysis was performed in accordance with the parameters of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) selecting only Phase III randomized clinical trials. The search strategy was constructed with the MeSH terms "Etanercept", "Biological Products", "Arthritis, Rheumatoid", "Biosimilar Pharmaceuticals" and was performed in Medline via PubMed, Embase, the Cochrane Library, Web of Science, EBSCO and Lilacs in January 2023. The analysis measures were relative risk (RR) for dichotomous data and mean difference (MD) for continuous data. The statistical analysis for preparing meta-analyses was developed by the Review Manager 5.1.4 software. RESULTS: This systematic review selected 6 eligible studies with a sample population of n = 2355. The main efficacy outcomes showed that both drugs did not present statistically significant differences in ACR20, ACR50, and ACR70 responses within 6 months (RR 1.00; 95% CI = 0.94 to 1.07; RR 1.09; 95% CI = 0.94 to 1.26; RR 1.04; 95% CI = 0.82 to 1.31, respectively), with I(2) ranging from 55 to 63% and 0.04 ≤ P ≥ 0.08. Adverse events were mostly mild or moderate, and serious adverse events were not statistically significant. Regarding immunogenicity, only 5.4% of the ADA-positive biosimilar group had positive neutralizing antibodies. CONCLUSIONS: Thus, this review found that biosimilar etanercept had efficacy, safety, and immunogenicity similar to those for the biological reference. SYSTEMATIC REVIEW REGISTRATION: This systematic review was registered on the PROSPERO platform under number CRD42020166610.