Disproportionality analysis of drug-associated progressive multifocal leukoencephalopathy using spontaneous reports:...

Area of Science:

• Pharmacovigilance and Drug Safety
• Neuroimmunology
• Epidemiology

Background:

• Progressive multifocal leukoencephalopathy (PML) is a rare, fatal demyelinating disease caused by JC virus reactivation in immunocompromised individuals.
• PML incidence is rising in non-HIV populations due to increased use of immunosuppressants and biologics.
• Real-world pharmacovigilance data is crucial for identifying drug-associated PML signals.

Purpose of the Study:

• To evaluate drug-associated PML reporting signals using real-world pharmacovigilance data.
• To identify high-risk drugs and indications associated with PML.
• To assess trends in PML reporting in non-HIV populations.

Main Methods:

• Analysis of the FAERS database from 2004Q1 to 2024Q4.
• Identification of PML reports using MedDRA Terms and manual validation.
• Application of four algorithms (ROR, PRR, BCPNN, MGPS) to detect drug signals, defining high-risk drugs as those with consistent signals across all four.

Main Results:

• 7,244 PML reports involving 298 drugs were identified.
• 72 drugs, primarily immunomodulators (e.g., natalizumab, rituximab), antineoplastics, and biologics, showed consistent PML signals.
• High-risk indications included multiple sclerosis, lymphoma, autoimmune diseases, and organ transplantation, with a substantial increase in non-HIV populations.

Conclusions:

• 72 drugs exhibited consistent PML reporting signals, suggesting potential associations.
• Findings represent statistical associations from spontaneous reports, not confirmed causality or incidence rates.
• Further prospective validation studies are necessary to establish causality and quantify risks.