A Programme for Risk Assessment and Minimisation of Progressive Multifocal Leukoencephalopathy Developed for Vedolizumab Clinical Trials.
A Programme for Risk Assessment and Minimisation of Progressive Multifocal Leukoencephalopathy Developed for Vedolizumab Clinical Trials.
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为维多珠单抗临床试验开发的风险评估和最小化进行性多灶性白质脑病的计划。
DOI：
10.1007/s40264-018-0669-8
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发表时间：
2018
期刊：
影响因子：
4.2
通讯作者：
Clifford,DavidB
中科院分区：
文献类型：
--
作者：
Parikh,Asit;Stephens,Kristin;Major,Eugene;Fox,Irving;Milch,Catherine;Sankoh,Serap;Lev,MichaelH;Provenzale,JamesM;Shick,Jesse;Patti,Mark;McAuliffe,Megan;Berger,JosephR;Clifford,DavidB
在过去的十年中，药物相关的进行性多灶性白质脑病（PML）的可能性已成为某些药物开发计划中越来越重要的考虑因素，特别是免疫调节生物制剂。无论研究药物的PML风险是否已得到证实（例如，从相关经验中推断，如类效应）或仅为理论，获得PML的严重后果都需要仔细的风险最小化和评估。这种风险最小化没有单一的标准。Vedolizumab是最近开发的α4β7整联蛋白单克隆抗体。作为全球批准前监管要求的一部分，其临床开发需要专门的PML风险最小化评估。本研究的目的是描述在炎症性肠病患者中进行的Vedolizumab临床试验中纳入的多个风险最小化要素，作为Vedolizumab风险评估和PML最小化计划的一部分。对符合临床疑似PML标准的受试者进行诊断评价。一个独立的裁决委员会提供了一个独立的，公正的意见，关于PML的可能性。ResultsAlthough没有病例被检测到，所有可疑的PML事件进行了彻底的审查，并成功地裁定，使它不太可能的情况下missed.ConclusionWe建议，该计划可以作为一个模式，务实的筛选PML在新药的临床开发。
IntroductionOver the past decade, the potential for drug-associated progressive multifocal leukoencephalopathy (PML) has become an increasingly important consideration in certain drug development programmes, particularly those of immunomodulatory biologics. Whether the risk of PML with an investigational agent is proven (e.g. extrapolated from relevant experience, such as a class effect) or merely theoretical, the serious consequences of acquiring PML require careful risk minimisation and assessment. No single standard for such risk minimisation exists. Vedolizumab is a recently developed monoclonal antibody to α4β7 integrin. Its clinical development necessitated a dedicated PML risk minimisation assessment as part of a global preapproval regulatory requirement.ObjectiveThe aim of this study was to describe the multiple risk minimisation elements that were incorporated in vedolizumab clinical trials in inflammatory bowel disease patients as part of the risk assessment and minimisation of PML programme for vedolizumab.MethodsA case evaluation algorithm was developed for sequential screening and diagnostic evaluation of subjects who met criteria that indicated a clinical suspicion of PML. An Independent Adjudication Committee provided an independent, unbiased opinion regarding the likelihood of PML.ResultsAlthough no cases were detected, all suspected PML events were thoroughly reviewed and successfully adjudicated, making it unlikely that cases were missed.ConclusionWe suggest that this programme could serve as a model for pragmatic screening for PML during the clinical development of new drugs.