Gepant drugs worked significantly better for acute migraine in women than men, while CGRP antibodies for prevention worked in both sexes.
NNT 11 in women vs 36 in menGepants needed to treat 11 women to achieve one additional pain-free response, but 36 men for the same result
What the researchers found
For acute migraine treatment, the three approved gepant drugs produced strong, statistically significant effects in women. The average drug effect for 2-hour pain freedom was 9.5% above placebo in women, with a number needed to treat of 11. In men, the average drug effect was only 2.8% above placebo and did not reach statistical significance. The number needed to treat in men was 36.
For migraine prevention, the picture was different. CGRP antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) and the oral preventive atogepant worked in both women and men for episodic migraine. In chronic migraine, the antibodies were similarly effective in both sexes.
Why it matters
Migraine affects women 3 times more than men, so most trial participants are women. If gepant drugs do not work as well in men, that is a significant clinical gap. This is one of the first analyses to systematically examine sex-based differences across the entire CGRP drug class.
The numbers in context
- Women: average 2-hour pain freedom drug effect 9.5% (CI: 7.4-11.6%), NNT = 11
- Men: average 2-hour pain freedom drug effect 2.8% (CI: -2.5 to 8.2%), NNT = 36
- Drug effect for women was always numerically greater than for men in every gepant study
- Preventive antibodies worked in both sexes for episodic and chronic migraine
How the study worked
Researchers conducted a subpopulation analysis using published FDA review data for all approved CGRP-targeting migraine drugs. They examined two-hour pain freedom and most bothersome symptom freedom for acute treatments, and change in monthly migraine days for preventive treatments. All data were separated by patient sex.
Who was studied
Male and female patients from FDA registration trials for all approved CGRP-targeting migraine drugs
What this study cannot tell us
This was a post-hoc subpopulation analysis of FDA data, not a prospective study designed to test sex differences. Men made up a small proportion of trial participants, reducing statistical power. The non-significant results in men could reflect low sample size rather than true lack of efficacy. Individual patient data was not available.
How to read the evidence
Rated moderate: uses FDA review data from multiple trials, providing a comprehensive picture, but this is a post-hoc subgroup analysis not designed to test sex differences.
When this study was published
Published in 2024 analyzing FDA approval data for all currently available CGRP-targeting drugs.
The bigger picture
Migraine affects women 3 times more than men, so men are underrepresented in trials. If gepants truly work less well in men, it represents a significant treatment gap for male migraine patients.
Questions still open
- Is the reduced effect in men real or due to small sample sizes?
- Should different acute treatments be recommended for men?
- What biological mechanism explains the sex difference?
Common questions
Do CGRP migraine drugs work for men?
Why might migraine drugs work differently by sex?
Read the original research
Evaluation of outcomes of calcitonin gene-related peptide (CGRP)-targeting therapies for acute and preventive migraine treatment based on patient sex.
Cephalalgia : an international journal of headache, 44(3), 3331024241238153
Citation
Porreca, Frank; Navratilova, Edita; Hirman, Joe; van den Brink, Antoinette Maassen; Lipton, Richard B; Dodick, David W. (2024). Evaluation of outcomes of calcitonin gene-related peptide (CGRP)-targeting therapies for acute and preventive migraine treatment based on patient sex.. Cephalalgia : an international journal of headache, 44(3), 3331024241238153. https://doi.org/10.1177/03331024241238153