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Peer-reviewedCC BY 4.0Frontiers in Neurology

Fifteen-year real-world pharmacovigilance of multiple sclerosis disease-modifying therapies: adverse event profiles, drug-specific safety signals and clinical implications

  • Sen Lin1,2
  • Bei Zhang1
  • Yingzhao Zhang3
  • Xinyu Zhang1
  • Yijia Li1
  • Weiqing Zhang4
  • Li He5
5 affiliations
  1. 1The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine
  2. 2The Chinese University of Hong Kong
  3. 3Department of Oncology, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine
  4. 4Department of Traditional Chinese Medicine, Shenzhen Longhua District People's Hospital
  5. 5Department of Oncology, Shenzhen Traditional Chinese Medicine Hospital
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Abstract

Background: Disease-modifying therapies (DMTs) are the cornerstone of remission-phase management for multiple sclerosis (MS), a prevalent autoimmune neuroinflammatory disorder of the central nervous system. However, their immune-modulating mechanisms carry inherent risks of systemic and neurological adverse events (ADEs), which remain a major barrier to optimal long-term care. This study aimed to comprehensively characterize the real-world safety profiles of all major MS DMT classes and identify clinically actionable safety signals.

Methods: We analyzed 15-year (2009Q1–2023Q4) ADE reports for 8 classes of FDA-approved MS DMTs from the FDA Adverse Event Reporting System (FAERS) database. Four disproportionality algorithms (ROR, PRR, BCPNN, MGPS) were used for signal detection. Time-to-onset (TTO) analysis with Weibull distribution and multivariate logistic regression were performed to assess temporal risk patterns and patient-specific risk factors for important medical events (IMEs).

Results: A total of 498,847 ADE reports (1,048,575 events) were included, with nearly 50% involving IMEs. The most common ADEs were systemic symptoms, infections, liver injury and alopecia. Notably, progressive multifocal leukoencephalopathy (PML, ROR = 15.59) and spontaneous abortion (ROR = 2.54) were identified as high-risk severe events. Drug-specific analysis revealed distinct safety signatures: anti-CD20 antibodies carried the highest infection risk, natalizumab was strongly associated with PML (ROR = 45.62), and teriflunomide had the highest alopecia risk (ROR = 12.73). Approximately 70% of IMEs occurred within 2 years of treatment initiation. Multivariate analysis identified older age, male sex and longer treatment duration as independent risk factors for IMEs, while obesity was a protective factor.

Conclusions: This long-term FAERS-based analysis identified potential safety signals associated with major MS DMTs, providing hypothesis-generating evidence to support clinical vigilance and prioritize further validation, but not to estimate incidence, comparative risk, or causality.

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Cite

BibTeXRIS
BibTeX
@article{lin2026fifteenyear,
  title = {{Fifteen-year real-world pharmacovigilance of multiple sclerosis disease-modifying therapies: adverse event profiles, drug-specific safety signals and clinical implications}},
  author = {Sen Lin and Bei Zhang and Yingzhao Zhang and Xinyu Zhang and Yijia Li and Weiqing Zhang and Li He},
  journal = {Frontiers in Neurology},
  year = {2026},
  month = oct,
  doi = {10.3389/fneur.2026.1845881},
  url = {https://www.frontiersin.org/articles/10.3389/fneur.2026.1845881/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Fifteen-year real-world pharmacovigilance of multiple sclerosis disease-modifying therapies: adverse event profiles, drug-specific safety signals and clinical implications
AU  - Sen Lin
AU  - Bei Zhang
AU  - Yingzhao Zhang
AU  - Xinyu Zhang
AU  - Yijia Li
AU  - Weiqing Zhang
AU  - Li He
PY  - 2026
DA  - 2026/10/13
JO  - Frontiers in Neurology
DO  - 10.3389/fneur.2026.1845881
UR  - https://www.frontiersin.org/articles/10.3389/fneur.2026.1845881/full
AB  - Background: Disease-modifying therapies (DMTs) are the cornerstone of remission-phase management for multiple sclerosis (MS), a prevalent autoimmune neuroinflammatory disorder of the central nervous system. However, their immune-modulating mechanisms carry inherent risks of systemic and neurological adverse events (ADEs), which remain a major barrier to optimal long-term care. This study aimed to comprehensively characterize the real-world safety profiles of all major MS DMT classes and identify clinically actionable safety signals.  Methods: We analyzed 15-year (2009Q1–2023Q4) ADE reports for 8 classes of FDA-approved MS DMTs from the FDA Adverse Event Reporting System (FAERS) database. Four disproportionality algorithms (ROR, PRR, BCPNN, MGPS) were used for signal detection. Time-to-onset (TTO) analysis with Weibull distribution and multivariate logistic regression were performed to assess temporal risk patterns and patient-specific risk factors for important medical events (IMEs).  Results: A total of 498,847 ADE reports (1,048,575 events) were included, with nearly 50% involving IMEs. The most common ADEs were systemic symptoms, infections, liver injury and alopecia. Notably, progressive multifocal leukoencephalopathy (PML, ROR = 15.59) and spontaneous abortion (ROR = 2.54) were identified as high-risk severe events. Drug-specific analysis revealed distinct safety signatures: anti-CD20 antibodies carried the highest infection risk, natalizumab was strongly associated with PML (ROR = 45.62), and teriflunomide had the highest alopecia risk (ROR = 12.73). Approximately 70% of IMEs occurred within 2 years of treatment initiation. Multivariate analysis identified older age, male sex and longer treatment duration as independent risk factors for IMEs, while obesity was a protective factor.  Conclusions: This long-term FAERS-based analysis identified potential safety signals associated with major MS DMTs, providing hypothesis-generating evidence to support clinical vigilance and prioritize further validation, but not to estimate incidence, comparative risk, or causality.
SN  - 1664-2295
ER  -