Do disease-modifying therapies for multiple sclerosis differ between male and female patients?

Sex Differences in Multiple Sclerosis Treatment

Current evidence demonstrates that sex influences MS treatment decisions and safety profiles, but disease-modifying therapies (DMTs) themselves do not differ in their fundamental efficacy between men and women—rather, prescribing patterns, tolerability, and treatment discontinuation rates vary by sex. 1

Treatment Efficacy: No Significant Sex Differences

The most recent guideline evidence from ECTRIMS and EBMT (2025) provides comprehensive recommendations for AHSCT and DMT use in MS but does not specify different treatment algorithms or drug choices based on sex 1. This absence of sex-specific recommendations in the highest-quality guideline reflects the current evidence base.

Real-world data confirms this approach:

• A 2026 Italian registry study found no significant differences between men and women in efficacy endpoints including confirmed disease progression risk, first relapse risk, and MRI active lesion risk for dimethyl fumarate, glatiramer acetate, beta interferon, natalizumab, and S1PR modulators 2
• The same DMTs are used for both sexes with similar effectiveness

Where Sex Does Matter: Safety and Treatment Decisions

Safety Profile Differences

Fingolimod shows the most robust sex-specific adverse event patterns:

• Women and younger patients have significantly higher risk of grade 3-4 lymphopenia (adjusted HR 0.33 for males, meaning women have 3x higher risk) 3
• Men have 3-fold higher risk of liver function test abnormalities (adjusted HR 3.10) 3
• First-dose bradycardia occurs equally (13.7%) regardless of sex or age 3

Glatiramer acetate:

• Men have significantly lower risk of withdrawal due to adverse events (HR 0.32, p=0.002) 2
• Dyspnea is the most common cause of discontinuation in both sexes 2

Prescribing Pattern Disparities

Critical finding: Treatment decisions are influenced by sex in ways that may not be clinically justified:

• Teratogenic DMTs (cladribine, sphingosine-1-phosphates, teriflunomide) are less likely to be prescribed to women aged 18-39 (OR 0.70) but not to women aged 40-49 4
• Women are less likely to escalate therapy despite relapse activity: probability of escalation per annualized relapse rate is HR 4.1 for women vs. HR 8.3 for men 5
• Women discontinue highly effective DMTs more frequently than men (HR 1.7), with family planning being the most common reason 5
• Younger women are more likely to discontinue moderate-effective DMTs (HR 1.03 per year), while older men are less likely to stop them (HR 0.92) 5

Clinical Implications and Pitfalls

Common Pitfalls to Avoid:

1. Under-treating women of childbearing age due to teratogenic concerns when they have aggressive disease requiring high-efficacy therapy—this represents a treatment disparity not supported by efficacy data 5, 4

2. Failing to escalate therapy appropriately in women despite equivalent disease activity to men 5

3. Not accounting for sex-specific adverse event risks when monitoring:

   • Monitor women on fingolimod more closely for lymphopenia 3
   • Monitor men on fingolimod more closely for hepatotoxicity 3
   • Anticipate higher discontinuation rates for glatiramer acetate in women 2

Practical Approach:

For women of childbearing potential:

• Do not automatically avoid teratogenic DMTs if disease activity warrants high-efficacy therapy
• When using teratogenic DMTs, ensure adequate contraception (hormonal LARC overlap remains low at only 2.52-fold higher than with interferons, suggesting room for improvement) 4
• Plan proactively for family planning rather than using it as a reason to under-treat

For monitoring:

• Implement sex-specific monitoring intensity for fingolimod (more frequent lymphocyte counts in women, more frequent LFTs in men) 3
• Recognize that women may report more tolerability issues with glatiramer acetate 2

For treatment escalation:

• Apply the same escalation criteria regardless of sex
• Be aware of unconscious bias toward less aggressive treatment in women 5

Evidence Limitations

The 2018 systematic review revealed that none of the Phase III pivotal trials for FDA/EMA-approved DMTs performed adequately powered, pre-specified analyses by sex 6. Recent trials have begun including post-hoc sex stratification, but this remains insufficient. The lack of sex-specific data in menopausal/older populations is particularly problematic 6.

Bottom line: Choose DMTs based on disease activity, disability progression, and individual risk-benefit assessment—not based on sex. However, adjust monitoring strategies and be vigilant about sex-based treatment disparities that may lead to under-treatment of women.