Progressive multifocal leukoencephalopathy after fingolimod treatment

Area of Science:

• Neuroimmunology
• Pharmacovigilance
• Demyelinating Diseases

Background:

• Fingolimod is used to treat multiple sclerosis.
• Progressive multifocal leukoencephalopathy (PML) is a rare, serious opportunistic infection of the brain.
• Understanding the risk of PML associated with fingolimod is crucial for patient safety.

Purpose of the Study:

• To characterize patients who developed fingolimod-associated PML.
• To estimate the risk and incidence of PML in patients treated with fingolimod.
• To identify any unique features of fingolimod-associated PML.

Main Methods:

• Searched the Novartis safety database for PML cases up to August 31, 2017.
• Classified PML cases based on established criteria.
• Estimated risk and incidence using 15 confirmed PML cases and the overall fingolimod-treated population.

Main Results:

• 15 fingolimod-treated patients developed PML without recent natalizumab use.
• Most patients were women (73%), with a mean age of 53 years.
• 14 patients had received fingolimod for over 2 years; none had sustained grade 4 lymphopenia.

Conclusions:

• The risk of PML with fingolimod, without prior natalizumab, is low (0.069 per 1,000 patients).
• The estimated incidence rate was 3.12 per 100,000 patient-years.
• No unique clinical or radiographic features distinguished fingolimod-associated PML.