Risk of progressive multifocal leukoencephalopathy in patients with multiple sclerosis treated with low-dose natalizumab following fingolimod

Objective

Progressive multifocal leukoencephalopathy (PML) may rarely develop in multiple sclerosis (MS) patients treated with certain disease-modifying drugs. A female patient weighing 40 kg developed PML with 12 copies/mL of prototype JC virus (JCV) DNA in the cerebrospinal fluid after 11 y of 4 mg/kg every 6 wk with natalizumab (NTZ) and intermittent holidays of fingolimod (FTY). The aim of this study was to analyze the PML risk of this case.

Methods

The lymphocyte subsets of CD4⁺ CD62L⁺ (central memory) and CD8⁺ CD62L⁻ (effector memory) were analyzed. Additionally, the total dosage per kg for 1 y before the onset of PML and the transition of the JCV index were assessed.

Results

In PML-naïve MS patients, both lymphocyte-subset counts decreased during FTY therapy but recovered after FTY cessation. However, in this PML patient the recovery took more than 2 y. In the PML patient, the JCV index increased by 1.17 over 1 y until 10 mo before the onset of PML.

Conclusions

Although each factor alone is not sufficient to pose a risk in our present PML patient, the presence of multiple factors may increase the risk of PML. Administering drugs such as NTZ, which carry a PML risk, to patients with a history of FTY treatment warrants caution. Dosage and interval adjustments of NTZ should be considered. Our study suggests the possibility that FTY may increase PML risk, highlighting the importance of considering the history of immunosuppressive drug therapy when administering NTZ in MS patients.