Molloy Eamonn S, Calabrese Leonard H
St. Vincent's University Hospital, Elm Park, Dublin, Ireland.
Arthritis Rheum. 2012 Sep;64(9):3043-51. doi: 10.1002/art.34468.
To evaluate the association of progressive multifocal leukoencephalopathy (PML) with immunosuppressive therapy for autoimmune rheumatic diseases (ARDs).
A Freedom of Information Act request was submitted for all cases of PML within the Food and Drug Administration Adverse Event Reporting System database. ARD cases were selected for further analysis.
A total of 34 confirmed cases of PML in the setting of ARDs were identified: 17 had systemic lupus erythematosus, 10 had rheumatoid arthritis, 4 had vasculitis, and 3 had dermatomyositis. Fifteen of these patients were treated with one or more biologic agents: 14 received rituximab (RTX), 6 received anti-tumor necrosis factor (anti-TNF) therapy (5 treated with anti-TNF agent prior to RTX). Four RTX-treated patients were not receiving additional immunosuppressive therapy at the time of PML onset, other than an antimalarial drug and/or low-dose glucocorticoids; all others who were receiving a biologic agent were also receiving one or more synthetic disease-modifying agents. All but 1 patient receiving a biologic agent had at least 1 potential confounding factor for the diagnosis of PML. The remaining 19 confirmed cases of PML among ARD patients were treated with synthetic disease-modifying antirheumatic drugs only, 14 of whom had received an alkylating agent.
PML has been reported in patients with ARD treated with various immunosuppressive agents. The limitations of this study preclude definitive attribution of causality. While the paucity of confirmed cases recently exposed to anti-TNF therapy suggests a causal relationship is unlikely, a specific signal is emerging with regard to rituximab and PML. Although this is a rare adverse event associated with RTX therapy, the devastating nature of PML mandates continued vigilance, particularly in patients with current or prior exposure to an alkylating agent.
评估进行性多灶性白质脑病（PML）与自身免疫性风湿性疾病（ARD）免疫抑制治疗之间的关联。
根据《信息自由法案》，向美国食品药品监督管理局不良事件报告系统数据库中的所有PML病例提出申请。选择ARD病例进行进一步分析。
共确定了34例ARD患者确诊为PML：17例患有系统性红斑狼疮，10例患有类风湿关节炎，4例患有血管炎，3例患有皮肌炎。其中15例患者接受了一种或多种生物制剂治疗：14例接受了利妥昔单抗（RTX）治疗，6例接受了抗肿瘤坏死因子（抗TNF）治疗（5例在接受RTX治疗前接受了抗TNF药物治疗）。4例接受RTX治疗的患者在PML发病时未接受其他免疫抑制治疗，仅服用了抗疟药和/或低剂量糖皮质激素；所有其他接受生物制剂治疗的患者也同时接受了一种或多种合成疾病改善药物治疗。除1例接受生物制剂治疗的患者外，所有患者在诊断PML时至少有1个潜在混杂因素。其余19例ARD患者确诊为PML的患者仅接受了合成抗风湿疾病药物治疗，其中14例接受了烷化剂治疗。
已有报道称，接受各种免疫抑制剂治疗的ARD患者中出现了PML。本研究的局限性使得无法明确因果关系。虽然近期接触抗TNF治疗的确诊病例较少，提示因果关系不太可能，但关于利妥昔单抗和PML的特定信号正在出现。虽然这是与RTX治疗相关的罕见不良事件，但PML的严重性要求持续保持警惕，尤其是在当前或既往接触过烷化剂的患者中。
