Presentation and Outcome in S1P-RM and Natalizumab-Associated Progressive Multifocal Leukoencephalopathy

Abstract

Background and ObjectivesProgressive multifocal leukoencephalopathy (PML) is a severe neurologic disease resulting from JC virus reactivation in immunocompromised patients. Certain multiple sclerosis (MS) diseasemodifying 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. MethodsA 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. ResultsOf 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 ). Overall, the outcome (mRS) at 12 months was similar in the 2 groups (OR: 0.81 [0.32-2.0]). Yet, posttreatment MS activity was higher in S1P-RM cases ).