Long-term progressive multifocal leukoencephalopathy risk stratification in multiple sclerosis patients treated with...

To evaluate the long-term follow-up in patients with multiple sclerosis (MS) with positive John Cunningham virus (JCV) index treated with natalizumab.

The prognosis in MS patients with positive JCV index in short-term follow-up is frequently analyzed; however, it is still not clear what the long-term outcomes in these patients are.

We performed retrospective chart review in MS patients with positive JCV index treated with natalizumab in the Department of Neurology, Medical University of Warsaw. According to the progressive multifocal leukoencephalopathy (PML) risk stratification algorithm established for MS patients treated with natalizumab, we have divided the patients included in our study into the following subgroups according to the JCV index results: JCV Index < 0.9, 0.9-1.5, > 1.5.

We have included 42 patients in our study, 28 females (67%), aged 42.9 ± 9.6 years, with mean disease duration of 13 ±7.07 years and median time of natalizumab therapy of 35 months. The most frequent indication for natalizumab use was lack of efficacy of disease-modifying drug (DMD) previously used (n = 29, 69%). The median extended disability status scale (EDSS) at the moment of last evaluation was 3.0 (range 0.0-8.5). In 14 patients (33.3%), the extended-interval dosing (EID) algorithm was implemented, while frequent brain magnetic resonance imaging (MRI) was done in 15 cases (36%). In one case, natalizumab-related serious adverse event (SAE) occurred, which was PML, but the patient survived and improved with time. When it comes to the number of patients belonging to each of the JCV subgroups, 18 (43%) were in the group with JCV index of < 0.9, 8 had intermediate JCV index (19%) and 16 (38%) had the JCV index > 1.5. There were no statistically significant differences concerning demographic data between the group with the lowest and moderate JCV index, only patients with the highest JCV index (> 1.5), were characterized by the highest disease duration (p = 0.0072). The EID algorithm was used in these cases significantly more frequently (p = 0.0023) than in the group with the lowest JCV index. Also, frequent MRI was performed significantly more often in this group (p = 0.0085). In the first group (JCV < 0.9), average variation of JCV index was between 0.17 and 0.34, in the second group (JCV 0.9-1.5) - between 1.03 to 1.54, and in the third group - between 2.6-2.8.

Based on our data, it can be concluded that long-term therapy with natalizumab seems to be safe, even in patients with positive JCV index.

Natalizumab can be used for long-term treatment of patients with MS even with positive JCV index if recommended precautions such as EID and frequent brain MRIs are followed.