Do CGRP Migraine Drugs Work Differently in Men and Women?

Gepant drugs worked significantly better for acute migraine in women than men, while CGRP antibodies for prevention worked in both sexes.

Porreca, Frank et al.·Cephalalgia : an international journal of headache·2024·Moderate Evidencesubgroup analysis
RPEP-09083Subgroup analysisModerate Evidence2024RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
subgroup analysis
Evidence
Moderate Evidence
Sample
Male and female patients from FDA registration trials for all approved CGRP-targeting migraine drugs
Participants
Male and female patients from FDA registration trials for all approved CGRP-targeting migraine drugs

What This Study 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.

Key Numbers

  • 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 They Did This

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.

Why This Research 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 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.

What This Study Doesn't 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.

Questions This Raises

  • ?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?

Trust & Context

Key Stat:
NNT 11 in women vs 36 in men Gepants needed to treat 11 women to achieve one additional pain-free response, but 36 men for the same result
Evidence Grade:
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.
Study Age:
Published in 2024 analyzing FDA approval data for all currently available CGRP-targeting drugs.
Original Title:
Evaluation of outcomes of calcitonin gene-related peptide (CGRP)-targeting therapies for acute and preventive migraine treatment based on patient sex.
Published In:
Cephalalgia : an international journal of headache, 44(3), 3331024241238153 (2024)
Database ID:
RPEP-09083

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study
What do these levels mean? →

Frequently Asked Questions

Do CGRP migraine drugs work for men?

Preventive CGRP antibodies work in both sexes. However, acute gepant drugs showed weaker, non-significant effects in men compared to women.

Why might migraine drugs work differently by sex?

Biological differences in CGRP signaling between men and women may play a role, but this is not yet fully understood.

Read More on RethinkPeptides

Cite This Study

RPEP-09083·https://rethinkpeptides.com/research/RPEP-09083

APA

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

MLA

Porreca, Frank, et al. "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, 2024. https://doi.org/10.1177/03331024241238153

RethinkPeptides

RethinkPeptides Research Database. "Evaluation of outcomes of calcitonin gene-related peptide (C..." RPEP-09083. Retrieved from https://rethinkpeptides.com/research/porreca-2024-evaluation-of-outcomes-of

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.