Disproportionality analysis of drug-associated progressive multifocal leukoencephalopathy using spontaneous reports: A 20-year signal detection study based on the FAERS database
Hailong Wang, Xinyi Li, Lijuan Shangguan
Abstract
Background
Progressive multifocal leukoencephalopathy (PML) is a rare, often fatal demyelinating disease caused by JC virus reactivation in immunocompromised patients. With the increasing use of immunosuppressants and biologics, PML reporting in non-HIV populations is rising. This study aimed to evaluate drug-associated PML reporting signals using real-world pharmacovigilance data.
Introduction
Progressive multifocal leukoencephalopathy (PML) is a rare and devastating central nervous system disease caused by reactivation of the JC virus (JCV) in immunosuppressed individuals. It typically presents with subacute onset of cognitive impairment, motor dysfunction, language disturbances, and visual field deficits, progressing rapidly with poor prognosis [1]. The diagnosis of PML relies on a combination of clinical manifestations, magnetic resonance imaging (MRI), and detection of JCV DNA in cerebrospinal fluid [2].
Materials and method
1. Data source and report identification
This study utilized data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database [21] (https://www.fda.gov/drugs/drug-approvals-and-databases/fda-adverse-event-reporting-system-faers-database), including all spontaneously reported adverse drug event records worldwide from the first quarter of 2004 to fourth quarter of 2024. The FAERS database contains multiple tables, including demographic (DEMO), drug (DRUG), indication (INDI), adverse reaction (REAC), and outcome (OUTC) information.
Results
1. Data screening and reports summary
From the FAERS database, a total of 18,613,992 unique patient records were extracted from the first quarter of 2004 to the fourth quarter of 2024 after data deduplication and multi-table integration. Further screening resulted in 7,244 drug-PML pairings, involving 298 drugs potentially associated with PML.
Discussion
This study systematically analyzed, based on the FAERS database, the epidemiological characteristics, drug signals, and clinical risk factors of drug-associated progressive multifocal leukoencephalopathy (PML) from 2004 to 2024.
Conclusion
This study systematically analyzed the reporting patterns of drugs-associated PML based on the FAERS database, observing a significant shift in PML report composition over the past two decades: while HIV/AIDS-related case reports remained stable, reports of drug-induced immunosuppression-related reports continued to increase and became predominant.
Citation: Wang H, Li X, Shangguan L (2026) Disproportionality analysis of drug-associated progressive multifocal leukoencephalopathy using spontaneous reports: A 20-year signal detection study based on the FAERS database. PLoS One 21(2): e0341855. https://doi.org/10.1371/journal.pone.0341855
Editor: Mehmet Baysal, Tekirdag Namik Kemal University: Tekirdag Namik Kemal Universitesi, TÜRKIYE
Received: August 30, 2025; Accepted: January 13, 2026; Published: February 3, 2026
Copyright: © 2026 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: The data analyzed in this study are publicly available from the US FDA Adverse Event Reporting System (FAERS; https://www.fda.gov/drugs/questions-and-answers-fdas-adverse-event-reporting-system-faers/fda-adverse-event-reporting-system-faers-public-dashboard). All data generated or analyzed during this study are included in this published article and its supplementary information files.
Funding: This work was supported by the Shanxi Provincial Department of Science and Technology, Basic Research Program (Free Exploration Category) — Youth Project [Grant No. 202403021222401, amount: CNY 50,000, received by SG LJ (Shang Guan Lijuan)]. Funder website: http://kjt.shanxi.gov.cn/. The sponsors/funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
