目的:进行性多灶性白质脑病(PML)是一种严重的神经系统疾病,由免疫功能低下患者的JC病毒再激活引起。某些多发性硬化症(MS)疾病改善疗法(DMT)与PML风险相关,例如那他珠单抗和,很少,鞘氨醇-1-磷酸受体调节剂(S1P-RM)。尽管那他珠单抗相关的PML有很好的记录,有关S1P-RM相关PML的信息有限。这项研究的目的是比较两组之间的临床表现和结果。
方法:一项回顾性多中心队列研究包括2009年至2022年接受S1P-RM或那他珠单抗治疗的PML患者。临床和放射学表现数据,结果,免疫重建炎症综合征(IRIS),生存,残疾(使用修改后的排名量表-mRS),和MS复发后PML进行分析。
结果:在88例患者中,分析了84例(20S1P-RM,64那他珠单抗)。S1P-RM相关的PML在老年患者中诊断(中位年龄52岁vs44岁,p<0.001)和更长的治疗时间(中位数为63.9vs40个月,p<0.001)。同样,S1P-RM患者在诊断时更容易出现症状(100vs80.6%,p=0.035),有更多的播散性病变(80%vs34.9%,p=0.002),并有更高的钆增强(65%对39.1%,p=0.042)。那他珠单抗患者的IRIS发育率较高(OR:8.3[1.92-33.3])。总的来说,两组12个月时的结局(mRS)相似(OR:0.81[0.32-2.0]).然而,S1P-RM病例治疗后MS活性较高(OR:5.7[1.4-22.2])。
结论:S1P-RM相关PML显示IRIS风险降低,但治疗后MS活性更高。临床医生应根据PML前药物调整PML后治疗。
OBJECTIVE: Progressive multifocal leukoencephalopathy (PML) is a severe neurologic disease resulting from JC virus reactivation in immunocompromised patients. Certain multiple sclerosis (MS) disease-modifying therapies (DMTs) are associated with PML risk, such as natalizumab and, more rarely, sphingosine-1-phosphate receptor modulators (S1P-RMs). Although natalizumab-associated PML is well documented, information on S1P-RM-associated PML is limited. The aim of this
study is to compare clinical presentations and outcomes between the 2 groups.
METHODS: A retrospective multicenter cohort
study included patients with PML from 2009 to 2022 treated with S1P-RMs or
natalizumab. Data on clinical and radiologic presentation, outcomes, immune reconstitution inflammatory syndrome (IRIS), survival, disability (using the modified Ranking scale-mRS), and MS relapses post-PML were analyzed.
RESULTS: Of 88 patients, 84 were analyzed (20 S1P-RM, 64
natalizumab). S1P-RM-associated PML was diagnosed in older patients (median age 52 vs 44 years, p < 0.001) and after longer treatment duration (median 63.9 vs 40 months, p < 0.001). Similarly, S1P-RM patients were more prone to show symptoms at diagnosis (100 vs 80.6%, p = 0.035), had more disseminated lesions (80% vs 34.9%, p = 0.002), and had higher gadolinium enhancement (65% vs 39.1%, p = 0.042).
Natalizumab patients had a higher IRIS development rate (OR: 8.3 [1.92-33.3]). Overall, the outcome (mRS) at 12 months was similar in the 2 groups (OR: 0.81 [0.32-2.0]). Yet, post-treatment MS activity was higher in S1P-RM cases (OR: 5.7 [1.4-22.2]).
CONCLUSIONS: S1P-RM-associated PML shows reduced IRIS risk but higher post-treatment MS activity. Clinicians should tailor post-PML treatment based on pre-PML medication.