Progressive multifocal leukoencephalopathy associated with sphingosine-1-phosphate receptor modulators: A large case...

Area of Science:

• Neurology
• Immunology
• Pharmacovigilance

Background:

• Risk factors for progressive multifocal leukoencephalopathy (PML) linked to sphingosine-1-phosphate receptor (S1PR) modulators require further characterization.
• Existing data on PML risk with S1PR modulators is less comprehensive compared to natalizumab.

Purpose of the Study:

• To characterize cases of PML associated with S1PR modulators.
• To identify and analyze risk factors for PML in patients using S1PR modulators.

Main Methods:

• Review of spontaneous adverse event reports from the FDA Adverse Event Reporting System (FAERS) database.
• Systematic review of the medical literature for reported PML cases associated with S1PR modulators.

Main Results:

• Identified 57 PML cases across all marketed S1PR modulators for multiple sclerosis; 53 cases involved fingolimod.
• Extended S1PR modulator exposure (≥18 months) emerged as a robust risk factor for PML.
• Patient age ≥50 years was a potential risk factor, and prior immunosuppressant exposure is proposed for further validation.

Conclusions:

• Spontaneous adverse event data confirm extended S1PR modulator exposure as a significant PML risk factor.
• Updated U.S. Prescribing Information for S1PR modulators reflects the identified risk.
• Further validation of potential risk factors is crucial for stratifying and mitigating PML risk.