Adverse Events Associated With Disease-Modifying Drugs for Multiple Sclerosis: A Multiregional Population-Based Study

Area of Science:

• Pharmacovigilance and Pharmacoepidemiology
• Neurology and Clinical Therapeutics
• Public Health and Health Services Research

Background:

• Randomized controlled trials (RCTs) have limitations in fully assessing the long-term safety of disease-modifying drugs (DMDs) for multiple sclerosis (MS).
• Short-term adverse events captured in RCTs may not reflect the full spectrum of risks associated with DMDs.
• Variability in reporting adverse events in clinical trials necessitates real-world safety evaluations.

Purpose of the Study:

• To examine the association between DMD exposure and potential adverse events in a large, multi-region, population-based cohort of individuals with MS.
• To establish a comprehensive real-world safety profile for various DMDs used in MS treatment.
• To inform clinical practice by providing insights into the risk-benefit profiles of different MS therapies.

Main Methods:

• Utilized linked administrative health data from four Canadian provinces to identify and follow 35,894 individuals with MS.
• Employed recurrent events proportional means models to assess associations between DMD exposure and infection-related hospitalizations/physician visits.
• Used stratified multivariate Cox proportional hazard models to evaluate associations between DMD exposure and 15 categories of incident adverse events.

Main Results:

• Most DMDs were associated with a significant reduction (42%-61%) in infection-related hospitalizations, but some showed a modest increase (10%-33%) in infection-related physician visits.
• Elevated risks for specific adverse events were observed with certain DMDs, including alemtuzumab (thyroid disorders, hypertension, cardiovascular disease), natalizumab (cardiovascular disease), fingolimod (cerebrovascular, ischemic heart diseases, hypertension), and teriflunomide (thyroid disorders, liver disease, hypertension, hyperlipidemia).
• Dimethyl fumarate showed an association with acute liver injury in complementary analyses.

Conclusions:

• This population-based study provides an extensive real-world safety profile for multiple DMDs used in MS treatment.
• Findings complement RCT data, offering new insights into the risk-benefit profiles of DMDs in clinical practice.
• Highlights the ongoing need for long-term, independent safety studies of DMDs for MS.