Landi Doriana, De Rossi Nicola, Zagaglia Sara, Scarpazza Cristina, Prosperini Luca, Albanese Maria, Buttari Fabio, Mori Francesco, Marfia Girolama Alessandra, Sormani Maria Pia, Capra Ruggero, Centonze Diego
From the Multiple Sclerosis Clinical and Research Unit, Department of Systems Medicine (D.L., M.A., F.B., F.M., G.A.M., D.C.), Tor Vergata University, Rome; IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed (D.L., M.A., F.B., F.M., G.A.M., D.C.), Pozzilli; Regional Multiple Sclerosis Center (N.D.R., C.S., R.C.), ASST-Spedali Civili di Brescia, Montichiari; Neurological Clinic (S.Z.), Marche Polytechnic University, Ancona; Department of Neurology and Psychiatry (L.P.), Sapienza University, Rome; and Biostatistics Unit, Department of Health Sciences (DISSAL) (M.P.S.), University of Genoa, Italy.
Neurology. 2017 Mar 21;88(12):1144-1152. doi: 10.1212/WNL.0000000000003740. Epub 2017 Feb 22.
To examine retrospectively the effects of plasmapheresis (PLEX) on the survival and clinical outcomes of patients with multiple sclerosis (MS) and natalizumab (NTZ)-associated progressive multifocal leukoencephalopathy (PML).
The medical literature was searched for the terms natalizumab and progressive multifocal leukoencephalopathy. A total of 193 international and 34 Italian NTZ-PML cases were included. Clinical outcome was determined by comparing the patients' clinical status at PML diagnosis with status after PML resolution. The effects on survival and clinical outcome of PLEX, sex, age, country, pre-PML Expanded Disability Status Scale score, NTZ infusion number, prior immunosuppressant exposure, PML symptoms, PML lesion location at diagnosis, CSF JC virus status and copies, additional PML treatments and steroids, and PML immune reconstitution inflammatory syndrome (IRIS) development were investigated with both univariate and multivariate analyses.
A total of 219 NTZ-PML cases were analyzed, and 184 (84%) underwent PLEX, which did not reduce the mortality risk or the likelihood of poor vs favorable outcomes. Country was predictive of mortality and poor outcome, while PML-IRIS development was predictive of poor outcome.
PLEX did not improve the survival or clinical outcomes of Italian or international patients with MS and NTZ-PML, suggesting that this treatment should be performed cautiously in the future.
This study provides Class III evidence that for patients with NTZ-PML, PLEX does not improve survival. The study lacks the statistical precision to exclude an important benefit or harm of PLEX.
回顾性研究血浆置换（PLEX）对多发性硬化症（MS）患者及那他珠单抗（NTZ）相关的进行性多灶性白质脑病（PML）患者生存率和临床结局的影响。
在医学文献中检索那他珠单抗和进行性多灶性白质脑病相关术语。共纳入193例国际及34例意大利NTZ-PML病例。通过比较患者PML诊断时的临床状态与PML缓解后的状态来确定临床结局。采用单因素和多因素分析研究PLEX、性别、年龄、国家、PML前扩展残疾状态量表评分、NTZ输注次数、既往免疫抑制剂暴露情况、PML症状、诊断时PML病变位置、脑脊液JC病毒状态及拷贝数、额外的PML治疗和类固醇以及PML免疫重建炎症综合征（IRIS）发生情况对生存率和临床结局的影响。
共分析219例NTZ-PML病例，其中184例（84%）接受了PLEX治疗，PLEX并未降低死亡风险或不良与良好结局的可能性。国家是死亡率和不良结局的预测因素，而PML-IRIS的发生是不良结局的预测因素。
PLEX并未改善意大利或国际MS合并NTZ-PML患者的生存率或临床结局，提示未来应谨慎进行这种治疗。
本研究提供III类证据，表明对于NTZ-PML患者，PLEX不能提高生存率。该研究缺乏排除PLEX重要益处或危害的统计精度。
