Fremanezumab

Additional information

Migraine is twice as common in women as in men [1-3]. In a Swedish population-based study the one-year prevalence was 9.5% in men and 16.7 % in women [4] which is slightly lower than three months prevalence reported from the US [1].

Among adults with migraine, sex and gender differences were found in a cross-sectional longitudinal internet-based study (11 049 women, 4 084 men). Compared with men, women had significantly higher amount of monthly headache days, were more likely to have been diagnosed with migraine and to report headache-related disability and cutaneous allodynia. Among prescription medication users, women took more triptans than men, while men were more likely to take opioids and, besides oral formulations, use nasal spray and injectable medication. Men also used more daily oral preventive medication than women [5].

Women who have migraine with aura have an increased risk of ischemic stroke compared to women without migraine [6]. A prospective controlled study showed that in patients with active migraine, female sex was significantly associated with the risk of ischemic stroke [7].

It should be noted that most studies include more women than men, and the low number of men included can affect the ability to make statistically significant analyses.

Pharmacokinetics and dosing

A pooled population pharmacokinetic analysis (2 192 women, 354 men) showed a trend towards marginally higher exposures of fremanezumab in women than in men. However, this was not found to be statistically significant [8].

The pharmaceutical company reports no differences in fremanezumab pharmacokinetics between men and women [9] and no sex differentiation in dosing has been recommended [9, 10].

Effects

The pharmaceutical company reports no differences regarding effect of fremanezumab between men and women [11], although the EPAR Public assessment report [12] states lower effect in men showed in a subgroup analysis of two pivotal studies [13, 14]. A significant effect was found on all dosing regimens on reduction in monthly average headache days and in monthly average migraine days for women, but not for men. According to the assessment report the applicant responded that this probably emanated from the small sample size in the male subgroup (<50 men per study arm) and that the analyses performed in the main studies were not statistically powered to examine efficacy in patient subgroups [12].

In the pivotal studies and other studies using data from the phase III randomized clinical trials no analyses of sex differences are reported [15-25].

Adverse effects

The incidence of side effects was similar in men and women according to the pharmaceutical company [11].

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).