School of Medicine, Flinders University, Bedford Park, GPO Box 2100, Adelaide, SA, 5001, Australia.
John Curtin School of Medical Research, Australian National University and Canberra Hospital, Canberra, ACT, Australia.
BioDrugs. 2018 Feb;32(1):27-52. doi: 10.1007/s40259-017-0256-z.
The efficacy, safety and immunogenicity risk of switching between an originator biologic and a biosimilar or from one biosimilar to another are of potential concern.
The aim was to conduct a systematic literature review of the outcomes of switching between biologics and their biosimilars and identify any evidence gaps.
A systematic literature search was conducted in PubMed, EMBASE and Cochrane Library from inception to June 2017. Relevant societal meetings were also checked. Peer-reviewed studies reporting efficacy and/or safety data on switching between originator and biosimilar products or from one biosimilar to another were selected. Studies with fewer than 20 switched patients were excluded. Data were extracted on interventions, study population, reason for treatment switching, efficacy outcomes, safety and anti-drug antibodies.
The systematic literature search identified 63 primary publications covering 57 switching studies. The reason for switching was reported as non-medical in 50 studies (23 clinical, 27 observational). Seven studies (all observational) did not report whether the reasons for switching were medical or non-medical. In 38 of the 57 studies, fewer than 100 patients were switched. Follow-up after switching went beyond 1 year in eight of the 57 studies. Of the 57 studies, 33 included statistical analysis of disease activity or patient outcomes; the majority of these studies found no statistically significant differences between groups for main efficacy parameters (based on P < 0.05 or predefined acceptance ranges), although some studies observed changes for some parameters. Most studies reported similar safety profiles between groups.
There are important evidence gaps around the safety of switching between biologics and their biosimilars. Sufficiently powered and appropriately statistically analysed clinical trials and pharmacovigilance studies, with long-term follow-ups and multiple switches, are needed to support decision-making around biosimilar switching.
在生物原研药和生物类似药之间以及从一种生物类似药转换到另一种生物类似药时，其疗效、安全性和免疫原性风险是潜在关注的问题。
本研究旨在对生物原研药和生物类似药之间以及从一种生物类似药转换到另一种生物类似药的转换结局进行系统文献回顾，并确定任何证据空白。
从建库至 2017 年 6 月，我们在 PubMed、EMBASE 和 Cochrane Library 中进行了系统文献检索，并对相关学会会议进行了检索。我们选择了报告关于生物原研药和生物类似药之间以及从一种生物类似药转换到另一种生物类似药的转换时的疗效和/或安全性数据的同行评议研究。排除了仅纳入少于 20 例转换患者的研究。我们提取了干预措施、研究人群、治疗转换的原因、疗效结局、安全性和抗药物抗体的数据。
系统文献检索确定了 63 项涵盖 57 项转换研究的主要出版物。50 项研究（23 项临床研究，27 项观察性研究）报告了转换的原因是非医疗性的。7 项研究（均为观察性研究）未报告转换原因是医疗性的还是非医疗性的。在 57 项研究中，有 38 项研究的转换患者少于 100 例。在 57 项研究中，有 8 项研究的随访时间超过 1 年。在 57 项研究中，有 33 项研究对疾病活动或患者结局进行了统计学分析；大多数研究发现，主要疗效参数（基于 P<0.05 或预定义的可接受范围）两组之间没有统计学显著差异，尽管一些研究观察到了某些参数的变化。大多数研究报告了两组之间相似的安全性概况。
在生物原研药和生物类似药之间以及从一种生物类似药转换到另一种生物类似药的安全性方面存在重要的证据空白。需要进行具有足够效力和适当统计学分析的临床试验和药物警戒研究，进行长期随访并进行多次转换，以支持关于生物类似药转换的决策。
