Global Product Development Medical Affairs, F. Hoffmann-La Roche Ltd, Basel, Switzerland; Department of Biomathematics, University of Thessaly School of Medicine, Larisa, Greece.
Department of Biomathematics, University of Thessaly School of Medicine, Larisa, Greece; Center for Clinical Evidence Synthesis, The Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA.
Clin Ther. 2019 Jan;41(1):155-173.e13. doi: 10.1016/j.clinthera.2018.11.002. Epub 2018 Dec 11.
In observational studies of patients switched from stable treatment with an originator monoclonal antibody (mAb) to a biosimilar, higher rates of biosimilar discontinuation versus those observed in blinded switching studies have been reported. Because this observation relates to the real-world setting, it has been suggested that switching outside of clinical trials may be associated with nocebo effects. However, real-world data on drug discontinuation and nocebo effects after switching to mAb biosimilars remain limited. This systematic review collated information from switching studies regarding discontinuation rates of biosimilar mAbs and investigated the subjectivity of reasons for discontinuation to determine the impact of potential nocebo responses.
MEDLINE (via PubMed), EMBASE, Cochrane Library, and abstract databases of selected congresses were screened for reports of mAb switching studies with a minimum post-switch follow-up ≥6 months and accessible information on discontinuation rates.
A total of 14 observational studies were included, all of which involved a switch to CT-P13. Ten interventional studies involving a switch to other biosimilar mAbs were excluded from the analysis because nocebo effects relate to the observational setting only. Eleven studies (78.6%) reported biosimilar discontinuation rates that were higher than expected based on data pertaining to long-term use of the originator infliximab and clinical trials involving a switch to CT-P13 (>10% per year; range, 12.2%-28.2%). Eight studies attributed a proportion of discontinuations to subjective disease worsening or subjective adverse events. Subjective adverse event reports were identified in 7 of the observational studies.
Discontinuation rates of biosimilar mAbs may increase due to subjective effects after switching from an originator mAb. These findings highlight the need for further patient education and well-designed, observational switching studies as well as the collection and analysis of identifiable pharmacovigilance and postmarketing data of biologics, including biosimilars. The collection of real-world results is particularly pertinent for mAbs other than CT-P13, for which there is currently a lack of observational switching data.
在观察性研究中，患者从稳定治疗的原研单克隆抗体（mAb）转为生物类似药时，与盲态切换研究中观察到的相比，生物类似药的停药率更高。由于这种观察与真实世界的情况有关，因此有人认为临床试验之外的切换可能与安慰剂效应有关。然而，关于转换为 mAb 生物类似药后的停药率和安慰剂效应的真实世界数据仍然有限。本系统评价汇总了关于生物类似药 mAb 停药率的切换研究信息，并调查了停药原因的主观性，以确定潜在安慰剂反应的影响。
通过 PubMed 中的 MEDLINE、EMBASE、Cochrane 图书馆以及选定大会的摘要数据库，筛选出至少有 6 个月随访期且可获得停药率信息的 mAb 切换研究报告。
共纳入 14 项观察性研究，均涉及 CT-P13 的切换。10 项涉及其他生物类似药切换的干预性研究因仅与观察性环境有关安慰剂效应而被排除在分析之外。11 项研究（78.6%）报告的生物类似药停药率高于基于长期使用原研英夫利昔单抗的数据和涉及 CT-P13 切换的临床试验所预期的停药率（每年>10%；范围，12.2%-28.2%）。8 项研究将部分停药归因于疾病主观恶化或主观不良事件。在 7 项观察性研究中发现了主观不良事件报告。
由于从原研 mAb 切换后的主观影响，生物类似药的停药率可能会增加。这些发现强调了需要进一步对患者进行教育，并开展设计良好的、观察性的切换研究，同时还需要收集和分析生物制剂（包括生物类似药）的可识别药物警戒和上市后数据。对于 CT-P13 以外的其他 mAb，收集真实世界的结果尤为重要，因为目前缺乏关于这些 mAb 的观察性切换数据。
