Efficacy and safety of erenumab in women with a history of menstrual migraine

DOI: https://doi.org/10.1186/s10194-020-01167-6

Abstract-Summary We performed a post hoc, subgroup analysis of a phase 3, randomized, double- blind, placebo-controlled study of erenumab for prevention of episodic migraine (STRIVE) to determine the efficacy and safety of erenumab in women with self- reported menstrual migraine.

Patients received placebo, erenumab 70  mg, or erenumab 140  mg subcutane- ously once monthly during the 6-month double- blind treatment phase of STRIVE.

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Women who reported history of menstrual migraine and who were ≤ 50 years old

were included in the analysis.

Among 814 women enrolled in STRIVE, 232 (28.5%) reported a history of men-

strual migraine and were ≤ 50 years old.

Between-group differences from placebo over months 4–6 for erenumab 70 mg and 140 mg were −1.8 (P = 0.001) and − 2.1 (P < 0.001) days for MMD and − 1.6 (P = 0.002) and −2.4 (P < 0.001) days for acute MSMD, respectively.

The odds of having a ≥ 50% reduction from baseline in MMD over months 4–6 were 2.2 (P = 0.024) and 2.8 (P = 0.002) times greater for erenumab 70  mg and 140 mg, respectively, than for placebo.

Data from this subgroup analysis of women with menstrual migraine are consis- tent with data from the overall STRIVE episodic migraine population, supporting the efficacy and safety of erenumab in women who experience menstrual migraine.

Background Women who experience migraine attacks with the majority of their menstrual peri- ods (defined by The International Classification of Headache Disorders [ICHD] 3 beta [254] as at least two of three periods) are classified into either pure menstrual migraine (PMM; attacks that occur only during the 5-day perimenstrual window) or menstrually related migraine (MRM; attacks that occur during the 5-day perimen- strual window and at other times of the cycle).

Long-term preventive treatment for menstrual migraine has been investigated with topiramate, which reduced the frequency but not the severity or duration of perimenstrual attacks [255].

Although hormonal contraceptives containing estrogens are considered a viable treatment option for women with menstrual migraine [256], evidence of their effec- tiveness is limited [257], and they may be contraindicated because of their associa- tion with increased risk of stroke [258–261].

The challenges associated with the treatment of menstrual migraine emphasize

the need for novel, nonhormonal, long-term preventive treatments.

Given the burden and challenges in the treatment of menstrual migraine, we performed a post hoc subgroup analysis of STRIVE to determine the efficacy and safety of erenumab in women with self-reported menstrual migraine.

Methods The study consisted of a 7-week screening phase (including 4 weeks of baseline), a 6-month double-blind treatment phase, a 7-month dose-blinded active treatment phase, and a 3-month safety follow-up phase.

Eligible patients were 18–65 years old with a history of migraine with or without aura (based on medical records and/or self- reported) for at least 12 months before screening.

Episodic migraine was defined as an average of 4–14 migraine days per month with fewer than 15 headache days per month (in accordance with ICHD-3) dur- ing the 3  months before screening and during the 4-week baseline phase of the study.

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Change from baseline in MMD and monthly acute MSMD was analyzed using a generalized linear mixed effects model, which included treatment, visit, treatment by visit interaction, stratification factors (North America/other and naïve/prior use/ concomitant use), and baseline value as covariates and assumed a first-order autore- gressive covariance structure; missing data were not imputed.

Results Of the 232 women with menstrual migraine, 65 (28%) were taking oral contracep- tives/hormone therapy during the study: 18 (26%) in the erenumab 70 mg group, 27 (33%) in the erenumab 140 mg group, and 20 (24%) in the placebo group.

The subgroup of patients receiving exogenous hormones had similar efficacy

results compared to the total population with a history of menstrual migraine.

A ≥50% response over months 4–6 was achieved by 25.3%, 42.6%, and 49.4% of patients who received placebo, erenumab 70  mg, and erenumab 140  mg, respectively.

Discussion Consistent with the overall STRIVE population, preventive treatment with ere- numab 70 mg and 140 mg vs placebo resulted in statistically significant improve- ments in MMD and acute MSMD and achievement of ≥50% response in this subpopulation of patients with a self-reported history of menstrual migraine.

The patients categorized as having menstrual migraine in our study have similar characteristics to “real-world” patients with menstrual migraine, who are generally identified based on retrospective self-report of perimenstrual migraine attacks dur- ing clinical encounters with the treating clinician rather than with prospective head- ache diaries.

Similar to the general population [262], approximately one-third of patients with menstrual migraine reported that they were taking oral contraceptives/hormone therapy during the study, which may be an important confounder in terms of effi- cacy in this subgroup of patients.

Acknowledgement A machine generated summary based on the work of Pavlovic, Jelena M.; Paemeleire, Koen; Göbel, Hartmut; Bonner, Jo; Rapoport, Alan; Kagan, Risa; Zhang, Feng; Picard, Hernan; Mikol, Daniel D. 2020 in The Journal of Headache and Pain.

A prospective real-world analysis of erenumab in refractory chronic migraine