类风湿关节炎患者中依那西普生物类似药与参照生物制剂的疗效、安全性及免疫原性：一项荟萃分析。

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

作者信息

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

机构信息

Department of Pharmacy, Karamay Central Hospital, Karamay, China.

Department of Nephropathy and Rheumatology, Karamay Central Hospital, Karamay, China.

出版信息

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

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). 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. 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), = 0.04, = 49%, high certainty], ACR50 at 1 year from PPS [3 RCTs, OR = 1.43 (1.10, 1.86), < 0.01, = 0%, high certainty] or FAS [2 RCTs, OR = 1.36 (1.04, 1.78), = 0.03, = 0%, high certainty], and ACR70 at 1 year from PPS [3 RCTs, OR = 1.32 (1.01, 1.71), = 0.04, = 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. 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. PROSPERO, identifier CRD42022358709.

尽管依那西普生物类似药已应用于类风湿关节炎领域，但其疗效、安全性和免疫原性的证据仍有限。我们进行了这项荟萃分析，以评估与参比生物制剂（恩利）相比，依那西普生物类似药治疗活动性类风湿关节炎的疗效、安全性和免疫原性。检索了PubMed、Embase、CENTRAL和ClinicalTrials.gov，以查找从最早记录到2022年8月15日诊断为类风湿关节炎的成年患者接受依那西普生物类似药治疗的随机对照试验。结局指标包括来自全分析集（FAS）或符合方案集（PPS）在不同时间点的美国风湿病学会（ACR）20、ACR50和ACR70缓解率、不良事件以及产生抗药抗体的患者比例。使用修订后的Cochrane随机试验偏倚风险工具评估每项纳入研究的偏倚风险，并根据推荐分级评估、制定和评价（GRADE）对证据的确定性进行评级。本荟萃分析纳入了6项随机对照试验，共2432例患者。从PPS分析，依那西普生物类似药在24周时的ACR50方面显示出更多益处[5项随机对照试验，比值比（OR）=1.22（1.01，1.47），P = 0.04，I² = 49%，高确定性]、在PPS分析1年时的ACR50方面[3项随机对照试验，OR = 1.43（1.10，1.86），P < 0.01，I² = 0%，高确定性]或FAS分析时[2项随机对照试验，OR = 1.36（1.04，1.78），P = 0.03，I² = 0%，高确定性]，以及在PPS分析1年时的ACR70方面[3项随机对照试验，OR = 1.32（1.01，1.71），P = 0.04，I² = 0%，高确定性]。在其他关于疗效、安全性和免疫原性的结局指标方面，结果显示依那西普生物类似药与参比生物制剂之间无显著差异，证据的确定性范围为低到中等。依那西普生物类似药在1年时的ACR50缓解率方面比参比生物制剂（恩利）显示出更多益处，依那西普生物类似药在类风湿关节炎患者中的其他临床疗效、安全性和免疫原性结局与原研药相当。国际前瞻性系统评价注册库（PROSPERO），标识符CRD42022358709。