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

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, I2 = 49%, high certainty], ACR50 at 1 year from PPS [3 RCTs, OR = 1.43 (1.10, 1.86), p < 0.01, I2 = 0%, high certainty] or FAS [2 RCTs, OR = 1.36 (1.04, 1.78), p = 0.03, I2 = 0%, high certainty], and ACR70 at 1 year from PPS [3 RCTs, OR = 1.32 (1.01, 1.71), p = 0.04, I2 = 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

Therapeutic Equivalence of Biosimilar and Reference Biologic Drugs in Rheumatoid Arthritis

“…To our knowledge, this is the largest systematic review to adequately examine the equivalence of biosimilars and reference biologics in RA. 30 Only 4 systematic reviews 20 , 25 , 28 , 29 of head-to-head trials comparing biosimilars and reference biologics in patients with RA have been published. As these reviews ignored the equivalence or noninferiority design of the primary studies, aiming to determine whether biosimilar drugs were superior to their reference biologics, our results are not directly comparable.…”

“…5,6,8,[13][14][15][16][17][18] Nonetheless, these recommendations have relied mainly on single trials or expert consensus, with only 2 guidelines using meta-analysis. 17,18 Previous systematic reviews [18][19][20][21][22][23][24][25][26][27][28][29] attempted to compile evidence on similar efficacy and safety between biosimilars and reference products for RA. Nonetheless, most of these reviews 18,19,21,23,24,27 provided only qualitative summaries, which are insufficient for decision-making.…”

“…Nonetheless, most of these reviews 18,19,21,23,24,27 provided only qualitative summaries, which are insufficient for decision-making. The few reviews 20,22,25,26,28,29 that attempted quantitative analyses did not use appropriate equivalence testing methods, resulting in imprecise conclusions. 30 In this study, we conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) comparing biosimilar drugs and reference products of the most prescribed TNFIs (infliximab, adalimumab, and etanercept) for RA.…”

“…Previous systematic reviews 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 attempted to compile evidence on similar efficacy and safety between biosimilars and reference products for RA. Nonetheless, most of these reviews 18 , 19 , 21 , 23 , 24 , 27 provided only qualitative summaries, which are insufficient for decision-making.…”

“…Nonetheless, most of these reviews 18 , 19 , 21 , 23 , 24 , 27 provided only qualitative summaries, which are insufficient for decision-making. The few reviews 20 , 22 , 25 , 26 , 28 , 29 that attempted quantitative analyses did not use appropriate equivalence testing methods, resulting in imprecise conclusions. 30 …”