North-Western Tuscany Blood Bank, Pisa University Hospital, Pisa, Italy.
Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Rev Med Virol. 2019 Nov;29(6):e2077. doi: 10.1002/rmv.2077. Epub 2019 Aug 1.
In 1997, rituximab was the first monoclonal antibody clinically approved for the treatment of cancer. Ten years later, progressive multifocal leukoencephalopathy (PML), until that time a rare opportunistic infection mostly seen in AIDS patients, was added as a black box warning after retrospective case-control studies showed an increased incidence in both B-cell lymphoproliferative disorders and autoimmune diseases. Despite more than 5 million worldwide exposures to date (and about 500 000 new exposures per year), insufficient data collection has hampered identification of risk minimization strategies, and concerns have been raised about a class effect extending to the newer anti-CD20 monoclonal antibodies (ofatumumab, obinutuzumab, and ocrelizumab). Here, we report current PML case counts registered in the FAERS and EudraVigilance databases and comment on severe CD4 T lymphopenia as a plausible common mechanism of action for anti-CD20 antibodies in causation of PML.
1997 年，利妥昔单抗成为首个被临床批准用于治疗癌症的单克隆抗体。十年后，进行回顾性病例对照研究后发现，在 B 细胞淋巴瘤和自身免疫性疾病中发病率增加，进展性多灶性白质脑病（PML）作为黑框警告被添加进来。在此之前，PML 一直是一种罕见的机会性感染，主要见于艾滋病患者。尽管迄今为止全球已有超过 500 万人（每年约有 50 万人）接触该药，但由于数据收集不足，无法确定降低风险的策略，人们担心这种类效应会扩展到新型抗 CD20 单克隆抗体（奥法妥珠单抗、奥瑞珠单抗和奥昔珠单抗）。在此，我们报告了 FAERS 和 EudraVigilance 数据库中目前登记的 PML 病例，并对严重的 CD4 T 淋巴细胞减少症发表评论，认为这可能是抗 CD20 抗体导致 PML 的共同作用机制。
