Erenumab

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

The pharmaceutical company reports no differences in erenumab pharmacokinetics between men and women [8-10] and no sex differentiation in dosing has been recommended [10, 11]. In a subgroup analysis of pooled data (84 men, 24 women)with both “healthy patients” (n=80) and migraine patients (n=28), no difference on clearance or volume of distribution of erenumab between men and women was found [12].

Effects

An uncontrolled longitudinal cohort study evaluated responsiveness to erenumab in patients with high-frequency episodic migraine or chronic migraine (70 men, 172 women). In patients with chronic migraine, they found a positive independent association between male sex and responsiveness (≥50% reduction from baseline in monthly headache days) with an odds ratio of 2.99 (95% CI: 1.03-8.7) [13]. The authors discuss that this might be due to the protective effect of testosterone in migraine, previously shown by worsened migraine by antiandrogen therapy in male-to-female transgender individuals [13].A subgroup analysis of a randomized controlled trial evaluated the efficacy of erenumab as a prophylactic medication in 232 women, 50 years or younger, with a reported history of menstrual migraine. The study showed that the efficacy of erenumab in women with menstrual migraine was consistent with the overall population from the randomized controlled trial [14].An observational case series with 18 fertile women showed that the proportion of headache days was higher in menstrual than in premenstrual and non-menstrual days in women who responded to erenumab (≥50% decrease in monthly headache days) (34.4% vs. 14.8% vs. 16.3%, respectively; p<0.001). The authors conclude that erenumab might improve menstrual migraine, but that menstruation still remains a trigger for migraine occurrence, even in the women who were responders to erenumab [15].

Adverse effects

An analysis of spontaneous reports to US Food and Drug Administration Adverse Event Reporting System Database (FAERS) on adverse events reported for erenumab, showed that a majority of the cases were reports in women, 15 099 (64.8%) cases out of total 23 312. The authors attributes this finding as a likely effect of the higher prevalence of migraine (and therefore erenumab use) among women [16].Safety of erenumab has been assessed in subpopulations, with sex differences as one of the evaluated intrinsic factors. In one subpopulation comprised by subjects from two phase-II studies [17, 18] and two phase-III studies [19, 20], 68 men (39%) and 443 women (51%) receiving placebo reported adverse events compared to 99 men (39%) and 665 women (49%) receiving erenumab. Men had lower incidence of reported adverse events compared to women, independent of dose of erenumab or type of migraine (chronic or episodic). The incidence of adverse events in women was however consistent with the overall population [9].In the subgroup analysis of a randomized controlled trial mentioned above, they also evaluated safety of erenumab in women with menstrual migraine. The overall safety profile was comparable to placebo and consistent with the overall population in the randomized controlled trial, except that this subgroup had no cardiovascular adverse events [14].

Reproductive health issues

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