Department of Health, Social and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, 84, Heukseokro, Dongjak-gu, Seoul, 156-756, South Korea.
College of Pharmacy, Gachon University, Inchon, South Korea.
BioDrugs. 2019 Oct;33(5):469-483. doi: 10.1007/s40259-019-00376-z.
Rituximab is a biologic medicine widely used for the treatment of autoimmune diseases and lymphoma. Several biosimilars of rituximab have been developed and marketed with the expiration of the originator rituximab's patent; thus, systematic combination and analysis of the latest data on the efficacy and safety of biosimilars and the demonstration of the interchangeability of biosimilar agents are required.
The objective of this study was to collate available data from head-to-head randomized controlled trials (RCTs) and evaluate the efficacy and safety of biosimilar rituximab compared with the reference drug in patients with rheumatoid arthritis (RA) and non-Hodgkin's lymphoma (NHL).
The PubMed, EMBASE, Cochrane Library, and Google Scholar databases were searched to identify head-to-head RCTs that directly compare the efficacy and safety of biosimilar rituximab and its originator. The efficacy outcome for RA was the American College of Rheumatology (ACR) response rates and the outcome for NHL was the response rate. The occurrence of adverse events (AEs) and anti-drug antibodies (ADAs) were evaluated for the safety outcome. Data on the pharmacokinetic profile were also included as a secondary outcome.
Eleven head-to-head RCTs with 3163 patients were included (1744 patients with RA and 1419 patients with NHL). Biosimilars of rituximab showed similar efficacy in the clinical response in both RA and NHL. The pooled risk ratio (RR) of the ACR 20% response rate (ACR20) response in patients with RA at weeks 24 and 48 was 0.99 (p = 0.70, 95% confidence interval [CI] 0.92-1.06) and 1.04 (p = 0.73, 95% CI 0.83-1.31), respectively. The pooled RR of the overall response at week 24 in NHL patients was 1.02 (p = 0.31, 95% CI 0.98-1.07). No significant differences were found in the formation of ADAs (RR 0.86, p = 0.20, 95% CI 0.68-1.08) or AEs (RR 1.04, p = 0.30, 95% CI 0.97-1.12).
This systematic review and conventional meta-analysis demonstrated the overall similarity of the long-term efficacy and safety of biosimilar rituximab to those of originator rituximab in RA and NHL patients by combining direct evidence from head-to-head trials. PROSPERO registration No. CRD42019125138.
利妥昔单抗是一种广泛用于治疗自身免疫性疾病和淋巴瘤的生物药物。随着原创利妥昔单抗专利的到期，已经开发并上市了几种利妥昔单抗的生物类似药；因此，需要系统地结合和分析生物类似药的最新疗效和安全性数据，并证明生物类似药的可互换性。
本研究旨在整理来自头对头随机对照试验（RCT）的可用数据，并评估生物类似利妥昔单抗与参考药物在类风湿关节炎（RA）和非霍奇金淋巴瘤（NHL）患者中的疗效和安全性。
检索 PubMed、EMBASE、Cochrane 图书馆和 Google Scholar 数据库，以确定直接比较生物类似利妥昔单抗及其原创药物疗效和安全性的头对头 RCT。RA 的疗效终点为美国风湿病学会（ACR）反应率，NHL 的疗效终点为缓解率。评估安全性终点的不良事件（AE）和抗药物抗体（ADA）的发生情况。还将药代动力学特征的数据作为次要终点纳入。
纳入了 11 项包含 3163 名患者的头对头 RCT（1744 名 RA 患者和 1419 名 NHL 患者）。生物类似利妥昔单抗在 RA 和 NHL 的临床反应中表现出相似的疗效。RA 患者在第 24 周和第 48 周时 ACR20 反应的汇总风险比（RR）为 0.99（p=0.70，95%置信区间 [CI] 0.92-1.06）和 1.04（p=0.73，95%CI 0.83-1.31），NHL 患者在第 24 周时的总缓解率的汇总 RR 为 1.02（p=0.31，95%CI 0.98-1.07）。未发现 ADA 形成（RR 0.86，p=0.20，95%CI 0.68-1.08）或 AE（RR 1.04，p=0.30，95%CI 0.97-1.12）存在显著差异。
通过对头对头试验的直接证据进行合并，本系统评价和常规荟萃分析表明，生物类似利妥昔单抗在 RA 和 NHL 患者中的长期疗效和安全性总体上与原创利妥昔单抗相似。PROSPERO 注册号：CRD42019125138。
