Efficacy, safety and immunogenicity of etanercept biosimilars versus reference biologics in patients with rheumatoid arthritis: A meta-analysis

Rui Hu; Tao Yuan; Hui Wang; Jianglin Zhao; Liya Shi; Quankai Li; Chunmei Zhu; Na Su; Shengzhao Zhang

doi:10.3389/fphar.2023.1089272

Efficacy, safety and immunogenicity of etanercept biosimilars versus reference biologics in patients with rheumatoid arthritis: A meta-analysis

Front Pharmacol. 2023 Feb 16:14:1089272. doi: 10.3389/fphar.2023.1089272. eCollection 2023.

Authors

Rui Hu¹, Tao Yuan¹, Hui Wang¹, Jianglin Zhao¹, Liya Shi¹, Quankai Li¹, Chunmei Zhu^{1

2}, Na Su^{3

4}, Shengzhao Zhang¹

Affiliations

¹ Department of Pharmacy, Karamay Central Hospital, Karamay, China.
² Department of Nephropathy and Rheumatology, Karamay Central Hospital, Karamay, China.
³ Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, China.
⁴ West China School of Pharmacy, Sichuan University, Chengdu, China.

Abstract

Background: Although with the application of etanercept biosimilars in the field of rheumatoid arthritis, the evidences of their efficacy, safety, and immunogenicity are still limited. We conducted this meta-analysis to evaluate the efficacy, safety and immunogenicity of etanercept biosimilars for treating active rheumatoid arthritis compared to reference biologics (Enbrel^®). Methods: PubMed, Embase, Central, and ClinicalTrials.gov were searched for randomized controlled trials of etanercept biosimilars treated in adult patients diagnosed with rheumatoid arthritis from their earliest records to 15 August 2022. The outcomes included ACR20, ACR50, and ACR70 response rate at different time points from FAS or PPS, adverse events, and proportion of patients developed anti-drug antibodies. The risk of bias of each included study was assessed using the revised Cochrane Risk of Bias in Randomised Trials tool, and the certainty of evidence was rated according to the Grading of Recommendation Assessment, Development, and Evaluation. Results: Six RCTs with 2432 patients were included in this meta-analysis. Etanercept biosimilars showed more benefits in ACR50 at 24 weeks from PPS [5 RCTs, OR = 1.22 (1.01, 1.47), p = 0.04, I ² = 49%, high certainty], ACR50 at 1 year from PPS [3 RCTs, OR = 1.43 (1.10, 1.86), p < 0.01, I ² = 0%, high certainty] or FAS [2 RCTs, OR = 1.36 (1.04, 1.78), p = 0.03, I ² = 0%, high certainty], and ACR70 at 1 year from PPS [3 RCTs, OR = 1.32 (1.01, 1.71), p = 0.04, I ² = 0%, high certainty]. In terms of other outcomes about efficacy, safety, and immunogenicity, the results showed that there was no significant difference between etanercept biosimilars and reference biologics, and the certainty of evidences ranged from low to moderate. Conclusion: Etanercept biosimilars showed more benefits in ACR50 response rate at 1 year than reference biologics (Enbrel^®), other outcomes for clinical efficacy, safety, and immunogenicity of etanercept biosimilars were comparable with originator in patients with rheumatoid arthritis. Systematic Review Registration: PROSPERO, identifier CRD42022358709.

Keywords: biosimilars; etanercept; meta-analysis; reference biologic; rheumatoid arthritis.

Publication types

Systematic Review

Grants and funding

This study sponsored by Karamay Central Hospital and Bethune Charitable Foundation (grant number YSP-2014). SZ was supported under grants from Xinjiang Natural Science Foundation (grant number 2022D01B194).