For Natalizumab-Associated PML, Prevention Is Still Key

Jeffrey M. Gelfand, MD, MAS

When progressive multifocal leukoencephalopathy does occur, patients who are asymptomatic at diagnosis have better outcomes.

Natalizumab, an anti-α4 integrin monoclonal antibody approved for treatment of multiple sclerosis (MS), is associated with excess risk for progressive multifocal leukoencephalopathy (PML), an opportunistic central nervous system infection caused by the JC virus. Diagnosis of PML is based on detection of JC virus in cerebrospinal fluid or on neuropathology. Most patients with PML present with progressive neurological worsening and typical features on magnetic resonance imaging (MRI), but some with MRI findings may be asymptomatic at diagnosis. Now, in a study supported by the manufacturer of natalizumab, researchers assessed outcomes in initially asymptomatic PML patients.

Among 372 cases of natalizumab-associated PML, 30 patients (8%) were deemed asymptomatic at diagnosis. Age, sex, MS duration, natalizumab exposure, and prior immunosuppressant therapy were similar in symptomatic and asymptomatic PML patients. Unilobar frontal lobe lesions on MRI were more common in asymptomatic patients. After the PML diagnosis, all patients stopped natalizumab, and 80% underwent plasma exchange. Survival was 97% in asymptomatic patients and 75% in symptomatic patients (mean follow-up, 13 and 11 months, respectively). Asymptomatic patients had less functional disability both at diagnosis and 6 months later, and 58% remained asymptomatic over a median of 16 months.

Citation(s):

Dong-Si T et al. Outcome and survival of asymptomatic PML in natalizumab-treated MS patients. Ann Clin Transl Neurol 2014 Oct; 1:755.