Fryklund Linda, Ritzén Martin, Bertilsson Göran, Arnlind Marianne Heibert
SBU, Box 3657, 103 59, Stockholm, Sweden,
Eur J Clin Pharmacol. 2014 May;70(5):509-17. doi: 10.1007/s00228-014-1655-4. Epub 2014 Feb 26.
The authors carried out a systematic and critical review of the scientific literature regarding the possible development of neutralising antibodies developed in patients treated with growth hormone biosimilars (defined as a drug expected to be similar to the originator or original pharmaceutical -European Medicines Agency) as compared to the reference drug. As a consequence, we discovered two major issues, namely, the poor quality of the comparative clinical trials and the poor quality of the antibody assays used during the trials.
The literature review was performed according to the principle of the Cochrane Collaboration and SBU. The electronic literature search included the databases PubMed, EMBASE and The Cochrane Library up to December 2012. Two independent reviewers assessed abstracts and full-text articles.
The search identified 1,553 abstracts related to the subject. Only six articles contained data on biosimilar growth hormone or antibody results obtained with appropriate methods. None of the studies fulfilled the criteria for high quality randomised controlled trials. Qualitative rather than quantitative assays were used for monitoring antibody formation.
It is our firm opinion , that since biosimilars are not identical, emphasis must be placed on the quality of the comparative clinical trials performed and the quality of the analytical studies in order to guarantee patient safety. Clinical trials should follow established quality rules for controlled comparative randomised clinical trials. A whole set of new guidelines is required.
作者对科学文献进行了系统且批判性的综述，内容涉及与参比药物相比，接受生长激素生物类似药（定义为预期与原创药或原研药相似的药物——欧洲药品管理局）治疗的患者体内可能产生的中和抗体情况。结果，我们发现了两个主要问题，即比较性临床试验质量欠佳以及试验期间所使用的抗体检测质量欠佳。
文献综述依据Cochrane协作网和瑞典卫生技术评估委员会（SBU）的原则进行。电子文献检索涵盖了截至2012年12月的PubMed、EMBASE和Cochrane图书馆数据库。两名独立评审员对摘要和全文文章进行评估。
检索共识别出1553篇与该主题相关的摘要。仅有6篇文章包含有关生物类似生长激素的数据或采用适当方法获得的抗体结果。没有一项研究符合高质量随机对照试验的标准。采用定性而非定量检测来监测抗体形成。
我们坚信，由于生物类似药并非完全相同，必须重视所开展的比较性临床试验的质量以及分析研究的质量，以确保患者安全。临床试验应遵循既定的对照比较随机临床试验质量规则。需要一整套新的指导原则。
