Department of Safety of Medicinal Products and Medical Devices, Paul-Ehrlich-Institute, Federal Institute for Vaccines and Biomedicines, Langen, Germany.
J Neurol Neurosurg Psychiatry. 2012 Sep;83(9):927-33. doi: 10.1136/jnnp-2012-302478. Epub 2012 Jul 17.
Novel immunosuppressive/modulating therapies with monoclonal antibodies (MABs) have been associated with progressive multifocal leukoencephalopathy (PML), a potentially fatal disease of the brain caused by the JC virus. Taking the complex diagnostic testing and heterogeneous clinical presentation of PML into account, an agreed case definition for PML is a prerequisite for a thorough assessment of PML.
OBJECTIVE/METHODS: A working group was established to develop a standardised case definition for PML which permits data comparability across clinical trials, postauthorisation safety studies and passive postmarketing surveillance. The case definition is designed to define levels of diagnostic certainty of reported PML cases following treatment with MABs. It was subsequently used to categorise retrospectively suspected PML cases from Germany reported to the Paul-Ehrlich-Institute as the responsible national competent authority.
The algorithm of the case definition is based on clinical symptoms, PCR for JC virus DNA in cerebrospinal fluid, brain MRI, and brain biopsy/autopsy. The case definition was applied to 119 suspected cases of PML following treatment with MABs and is considered to be helpful for case ascertainment of suspected PML cases for various MABs covering a broad spectrum of indications. Even if the available information is not yet complete, the case definition provides a level of diagnostic certainty.
The proposed case definition permits data comparability among different medicinal products and among active as well as passive surveillance settings. It may form a basis for meaningful risk analysis and communication for regulators and healthcare professionals.
新型免疫抑制/调节治疗药物（单抗）与进行性多灶性白质脑病（PML）有关，PML 是一种由 JC 病毒引起的潜在致命性脑疾病。考虑到 PML 的复杂诊断检测和异质临床表现，PML 的公认病例定义是全面评估 PML 的前提。
目的/方法：成立了一个工作组，制定了 PML 的标准化病例定义，以允许在临床试验、上市后安全性研究和被动上市后监测中进行数据比较。该病例定义旨在定义在接受单抗治疗后报告的 PML 病例的诊断确定性水平。随后，它被用于对德国向保罗-埃利希研究所报告的疑似 PML 病例进行回顾性分类，作为负责的国家主管当局。
病例定义的算法基于临床症状、脑脊液 JC 病毒 DNA 的 PCR、脑 MRI 和脑活检/尸检。该病例定义应用于 119 例接受单抗治疗后疑似 PML 的病例，被认为有助于对各种单抗治疗的疑似 PML 病例进行病例确定，涵盖了广泛的适应证。即使可用信息尚不完全，该病例定义也提供了一定的诊断确定性。
拟议的病例定义允许不同药物之间以及主动和被动监测环境之间进行数据比较。它可以为监管机构和医疗保健专业人员进行有意义的风险分析和沟通提供基础。
