Age as a risk factor for early onset of natalizumab-related progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a rare but potentially fatal opportunistic infection that arises almost exclusively in immunocompromised patients or in those treated with monoclonal antibodies, especially natalizumab. Here, we aimed at exploring if age at treatment start affects the time to onset of natalizumab-related PML. PubMed was searched for the terms "natalizumab and progressive multifocal leukoencephalopathy" in articles published from January 2005 to March 2017. We collected information on each identified PML case, including demographic and clinical variables at natalizumab start and at PML onset. The number of natalizumab infusions until PML onset was investigated in time-to-event analyses. We identified 238 cases who developed PML after a median number of 33 natalizumab infusions (range 6 to 103). Risk factors for an earlier onset of natalizumab-related PML were prior immunosuppressant exposure (hazard ratio [HR] = 1.43, p = 0.017) and older age at treatment start (HR = 1.02, p = 0.016). In particular, patients older than 50 years had a more than doubled-increased risk for an earlier PML onset (HR = 2.11, p = 0.006). Our findings suggest that the age at natalizumab start may represent a risk factor for an earlier PML onset, thus claiming further investigations about the interplay between immunosenescence and MS treatments.