Immunogenicity of biologic therapies in psoriasis: Myths, facts and a suggested approach.
Immunogenicity of biologic therapies in psoriasis: Myths, facts and a suggested approach.
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银屑病生物疗法的免疫原性：神话、事实和建议的方法。
DOI：
10.1111/jdv.16980
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Tsakok T
中科院分区：
文献类型：
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作者：
Tsakok T
随着生物药物主导严重免疫介导的炎症性疾病的治疗空间，临床医生熟悉药物免疫原性的概念至关重要，因为我们的患者可能会产生具有临床意义的抗药抗体（ADA）。虽然不同治疗性生物制剂在报告的ADA发生率方面存在明显差异，但尚无公认的皮肤病学指南或按临床相关ADA风险对药物进行分组，也未就ADA管理方法达成共识。这部分是因为对药物之间的免疫原性进行有效比较存在根本性缺陷：ADA检测的不同类型、试验设计和纳入的患者人群-以及生物分子本身的分子结构-都对报告的ADA患病率和对临床应答的影响有很大影响。因此，本文的第一部分旨在概述ADA，同时澄清对该主题的常见误解，而本文的第二部分概述了银屑病（最常见的皮肤病适应症）常用生物制剂的III期免疫原性数据。基于这一点，并承认现有证据的局限性，我们提出了一个生物制品的工作分类以及一个广泛的管理方法：第1组-具有较高临床相关ADA风险的生物制品;第2组-具有较低临床相关ADA风险的生物制品;第3组-没有确定临床相关ADA风险的生物制品。然而，这些分组仅代表一个工作概念;需要更多的研究，使用可比的ADA检测和相关结果的一致性报告。最后，迫切需要更好地表征具有发生ADA特定风险的个体，以告知未来的临床决策。
With biologic drugs dominating the therapeutic space for severe immune‐mediated inflammatory disease, it is critical for clinicians to be familiar with the concept of drug immunogenicity, with the potential for our patients to develop antidrug antibodies (ADA) of clinical relevance. Whilst there are clear differences between different therapeutic biologics in terms of reported ADA rates, there is no accepted dermatology guideline or grouping of drugs by risk of clinically relevant ADA, nor a consensus on approach to ADA management. This is partly because making valid comparisons of immunogenicity across drugs is fundamentally flawed: the differing types of ADA assay, trial design and included patient population – as well as the molecular structure of the biologic molecules themselves – are all highly influential on reported ADA prevalence and impact on clinical response. Therefore, the first part of this article aims to give an overview of ADA that also clarifies common misconceptions on the subject, whilst the second part of this article outlines Phase III immunogenicity data on commonly used biologics for psoriasis, the most common dermatological indication. Based on this, and acknowledging current limitations in available evidence, we propose a working categorization of biologics together with a broad approach to management: Group 1 – biologics with higher risk of clinically relevant ADA; Group 2 – biologics with lower risk of clinically relevant ADA; and Group 3 – biologics with no established risk of clinically relevant ADA. However, these groupings represent a working concept only; more research is required, using comparable ADA assays and consistent reporting of related outcomes. Finally, there is an urgent need for better characterization of individuals at particular risk of developing ADA to inform future clinical decision‐making.