Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Via Consolare Valeria, Messina, Italy.
Unit of Clinical Pharmacology, A.O.U. Policlinico "G. Martino", Messina, Italy.
Drug Saf. 2018 Nov;41(11):1013-1022. doi: 10.1007/s40264-018-0684-9.
In recent years, marketing of highly innovative and costly biologics improved the management of high-burden diseases such as autoimmune diseases, cancers, and chronic renal failure. Several widely prescribed biologics have recently lost or will shortly lose their patents, thus opening avenues to the marketing of a growing number of biosimilars worldwide, which are products similar in terms of quality, safety, and efficacy to already licensed reference products, thus allowing for potential savings in pharmaceutical expenditure. Numerous debates about the interchangeability between biosimilars and reference products are still ongoing, owing to concerns about potential immunogenicity raised by switching, which may cause a lack of effect and toxicity. Patients successfully treated with biologic therapy may theoretically receive biosimilars to contain costs, if reference product and related biosimilar are judged as interchangeable. However, the positions of regulatory agencies on the interchangeability and automatic substitution of biologics with biosimilars are very different. The benefit-risk profile of biosimilars has been often questioned by clinicians owing to the limited amount of pre-marketing information on clinical efficacy and safety, despite biosimilarity being based on a comparability exercise with the reference product to gain the biosimilar approval. Nevertheless, after more than 10 years of marketing from the first biosimilar approval in Europe, no proof of differences in terms of the safety profile of biosimilars and originators has been reported. In this context, post-marketing evaluation of both biologics and biosimilars safety profiles through analyses from spontaneous reporting databases and claims databases is crucial. An important issue for the pharmacovigilance of biologics concerns the traceability, indicating the brand name and batch number in spontaneous adverse drug reaction reports, but this requirement is not frequently addressed. This review aims to provide an overview of the characteristics and potential challenges in the safety profile assessment of biologics with a focus on the post-marketing setting.
近年来，高度创新和昂贵的生物制剂的营销改善了自身免疫性疾病、癌症和慢性肾衰竭等高负担疾病的管理。最近，一些广泛使用的生物制剂已经或即将失去专利，从而为全球越来越多的生物类似药的营销开辟了道路，这些生物类似药在质量、安全性和疗效方面与已获得许可的参比产品相似，从而有可能节省药物支出。由于担心转换可能导致的潜在免疫原性，生物类似药和参比产品之间的可互换性仍存在诸多争议，这可能导致疗效和毒性缺失。如果参照产品和相关的生物类似药被判断为可互换，那么接受生物制剂治疗成功的患者理论上可以接受生物类似药来控制成本。然而，监管机构对生物类似药的可互换性和自动替代的立场差异很大。由于在临床疗效和安全性方面的上市前信息有限，生物类似药的获益-风险状况经常受到临床医生的质疑，尽管生物类似性是基于与参比产品的可比性研究来获得生物类似药的批准。尽管如此，在欧洲第一个生物类似药获得批准后，已经过去了 10 多年，但是还没有报告关于生物类似药和原研药安全性方面的差异。在这种情况下，通过自发报告数据库和理赔数据库对生物制剂和生物类似药安全性概况进行上市后评估至关重要。生物制剂药物警戒的一个重要问题是可追溯性，即在自发药物不良反应报告中表明品牌名称和批次号，但这一要求并不经常得到满足。本文旨在概述生物制剂安全性概况评估的特点和潜在挑战，重点是上市后评估。
