Are CGRP medications effective against migraine in men?

Via Medscape: Most patients with migraine are women. This female predominance is reflected in the clinic and in clinical trials, where ~85% are women. A pharmacologist and a neurologist from the United States argue that the efficacy of calcitonin gene-related peptide (CGRP)-based migraine therapies has been proven in women but not in men, and that men should be informed of this.

In their article, which was published in JAMA Neurology, Frank Porreca, PhD, associate head of pharmacology at the University of Arizona in Tucson, and David W. Dodick, MD, professor emeritus of neurology at the Mayo Clinic Arizona in Phoenix, refer to medication that targets CGRP or its receptors.

Porreca and Dodick base their argument that CGRP-based therapies, especially the new active-substance class of gepants, are less effective in men than in women on preclinical data:

  • In mice, the injection of CGRP directly into the dura mater led to migraine-like headaches. Much lower doses were required for this in female animals than in males.
  • CGRP antibodies alleviate migraine-like pain in female mice considerably better than they do in male mice.

They also drew on observations from human studies:

  • One study with seven women and one man showed that in women, the CGRP level was elevated during a migraine attack and could be normalised again with sumatriptan. In the man, the levels were not elevated, nor could they be reduced through the application of the triptan.
  • Provocation studies, in which migraine headaches were triggered through an infusion of CGRP to prove its role in the formation of migraines, were conducted almost exclusively in women.
  • Pooled data on ubrogepant and rimegepant showed no therapeutic benefit in men. While ubrogepant demonstrated a therapeutic benefit, compared with placebo, in 8.3% (freedom from pain) and 12.4% (burdensome symptom after 2 hours) of women, a benefit was only observed in 0.2% or 0.7% of men, compared with placebo. Similar results were seen in studies of rimegepant.