Kommersiellt obunden läkemedelsinformation riktad till läkare och sjukvårdspersonal

Erenumab

Klassificering: A

Preparat: Aimovig

ATC kod: N02CD01

Substanser: erenumab

Sammanfattning

Det saknas kontrollerade studier om skillnader mellan könen avseende effekt och säkerhet. En okontrollerad klinisk studie har visat bättre effekt hos män med kronisk migrän än hos kvinnor. Högre andel spontanrapporterade biverkningar har setts hos kvinnor jämfört med män. Erenumab tycks ha liknande effekt och säkerhet hos kvinnor med menstruell migrän som hos den generella befolkningen.

Additional information

Migraine is almost twice as common in women as in men [2, 3]. In a Swedish population- based study the one-year prevalence was 16.7 % in women and 9.5 % in men [4] which is slightly lower than three months prevalence reported from the US [2]. 

Women who have migraine with aura have an increased risk of ischemic stroke compared to women without migraine [4]. A prospective controlled study showed that in patients with active migraine, female sex was significantly associated with the risk of ischemic stroke [5].

Pharmacokinetics and dosing

The pharmaceutical company reports no differences in erenumab pharmacokinetics between men and women [6-8] and no sex differentiation in dosing has been recommended [8, 9]

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 [10].

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) [11]. 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 [11].

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 [12].

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 [13].

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 [14].

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 [15, 16] and two phase-III studies [17, 18], 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 [7].

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 [12].

Reproductive health issues

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

Försäljning på recept

Fler kvinnor än män hämtade ut läkemedel innehållande erenumab (ATC-kod N02CD01) på recept år 2020, totalt 2 595 kvinnor och 555 män. Det motsvarar 5 respektive 1 person(er) per tiotusen invånare. Andelen som fått läkemedel var högst i åldersgruppen 45–54 år hos kvinnor och 50–54 år hos män. I genomsnitt var läkemedel innehållande erenumab 5 gånger vanligare hos kvinnor [19].

Uppdaterat: 2021-11-17

Litteratursökningsdatum: 2021-09-20

Referenser

  1. Stovner LJ, Andree C. Prevalence of headache in Europe: a review for the Eurolight project. J Headache Pain. 2010;11(4):289-99. PubMed
  2. Smitherman TA, Burch R, Sheikh H, Loder E. The prevalence, impact, and treatment of migraine and severe headaches in the United States: a review of statistics from national surveillance studies. Headache. 2013;53(3):427-36. PubMed
  3. Dahlöf C, Linde M. One-year prevalence of migraine in Sweden: a population-based study in adults. Cephalalgia. 2001;21:664-71. PubMed
  4. Kurth T, Slomke MA, Kase CS, Cook NR, Lee IM, Gaziano JM, et al. Migraine, headache, and the risk of stroke in women: a prospective study. Neurology. 2005;64(6):1020-1026. länk
  5. Milhaud D, Bogousslavsky J, van Melle G, Liot P. Ischemic stroke and active migraine. Neurology. 2001;57(10):1805-11. PubMed
  6. DailyMed Aimovig (erenumab). DailyMed [www]. US National Library of Medicine. [updated 2021-05-19, cited 2021-09-20]. länk
  7. EMA. Aimovig. Scientific Assessment Report 2019-02-18. Scientific Assessment Report. 2019-02-28.
  8. Food and Drug Administration (FDA). Summary Review - AIMOVIG (erenumab). Drugs@FDA [www]. [updated 2015-05-15, cited 2021-10-14]. länk
  9. Aimovig (erenumab). Summary of Product Characteristics. European Medicines Agency (EMA) [updated 2021-10-28, cited 2021-09-20]
  10. Vu T, Ma P, Chen JS, de Hoon J, Van Hecken A, Yan L et al. Pharmacokinetic-Pharmacodynamic Relationship of Erenumab (AMG 334) and Capsaicin-Induced Dermal Blood Flow in Healthy and Migraine Subjects. Pharm Res. 2017;34(9):1784-1795. PubMed
  11. Barbanti P, Aurilia C, Cevoli S, Egeo G, Fofi L, Messina R et al. Long-term (48 weeks) effectiveness, safety, and tolerability of erenumab in the prevention of high-frequency episodic and chronic migraine in a real world: Results of the EARLY 2 study. Headache. 2021;61(9):1351-1363. PubMed
  12. Pavlovic JM, Paemeleire K, Göbel H, Bonner J, Rapoport A, Kagan R, et al. Efficacy and safety of erenumab in women with a history of menstrual migraine. J Headache Pain. 2020;21(1):95. länk
  13. Ornello R, Frattale I, Caponnetto V, De Matteis E, Pistoia F, Sacco S. Menstrual Headache in Women with Chronic Migraine Treated with Erenumab: An Observational Case Series. Brain Sci. 2021;11(3):370. länk
  14. Sessa M, Andersen M. New Insight on the Safety of Erenumab: An Analysis of Spontaneous Reports of Adverse Events Recorded in the US Food and Drug Administration Adverse Event Reporting System Database. BioDrugs. 2021;35(2):215-227. PubMed
  15. Study to Evaluate the Efficacy and Safety of Erenumab (AMG 334) in Migraine Prevention. Clinicaltrialsgov [www]. [updated 2021-09-28, cited 2021-10-26]. länk
  16. A Study to Evaluate the Efficacy and Safety of Erenumab (AMG 334) in Chronic Migraine Prevention. Clinicaltrialsgov [www]. [updated 2019-12-17, cited 2021-10-26]. länk
  17. Study to Evaluate the Efficacy and Safety of Erenumab (AMG 334) in Migraine Prevention (STRIVE). Clinicaltrialsgov [www]. [updated 2019-10-09, cited 2021-10-26]. länk
  18. Statistikdatabas för läkemedel. Stockholm: Socialstyrelsen. 2020 [cited 2021-03-10.] länk

Författare: Maria Ljungdahl

Faktagranskat av: Diana Rydberg

Godkänt av: Karin Schenck-Gustafsson