Frontiers in immunology
Non-PML neuroinvasive infections reported with multiple sclerosis disease-modifying therapies: a mechanism-based pharmacovigilance study, 2004-2025
By Ke L, Jiang S, Duan J and 1 others.
Abstract
Background
Multiple sclerosis (MS) disease-modifying therapies (DMTs) alter host immunity and may produce pathogen-specific susceptibility to neuroinvasive infection. Comparative evidence is limited because events are rare and postmarketing research focuses mainly on progressive multifocal leukoencephalopathy (PML).
Methods
We analyzed deduplicated US FDA Adverse Event Reporting System (FAERS) reports from 2004Q1 to 2025Q4 using a prespecified case-non-case design. Tier A comprised direct high-certainty non-PML neuroinvasive infection terms. Tier B comprised a possible CNS infectious syndrome plus pathogen evidence elsewhere in the report, without CNS confirmation; tier A+B was a lower-certainty expanded endpoint for sensitivity and pathogen composition analyses. We estimated overall reporting (E1), pathogen composition within tier A+B (E2), and same-pathogen CNS localization (E3). Five DMT mechanisms were compared with contemporaneous active DMTs using calendar-year Mantel-Haenszel reporting odds ratios and covariate-adjusted Jeffreys-prior penalized logistic models.