Last reviewed: September 2018
Last updated: August  2018

FDA approves three CGRP inhibitors for the prevention of migraine

Erenumab, fremanezumab, and galcanezumab, novel treatments for migraine prevention, have received approval from the Food and Drug Administration (FDA) for use in adults in May (erenumab) and September (fremanezumab, galcanezumab) 2018. These new agents are fully human monoclonal antibodies that work by inhibiting the calcitonin gene‑related peptide (CGRP) receptors. The CGRP is believed to play a causal role in the pathophysiology of migraine. They are administered subcutaneously.

  • Erenumab: in two trials involving 667 patients with chronic migraine and 955 with episodic migraine, patients with chronic migraine showed an average reduction of 2.5 monthly migraine days compared with placebo after 3 months of treatment. For patients with episodic migraine the reduction was either 1.3 or 1.8 days, depending on the dose taken.The most common side effects were injection site reactions, constipation, muscle spasms, and pruritus.

  • Fremanezumab: in two trials involving 1130 patients with chronic migraine and 875 with episodic migraine, patients with chronic migraine showed an average reduction of 2.1 (monthly dosing) or 1.8 (quarterly dosing) monthly migraine days compared with placebo after 3 months of treatment. For patients with episodic migraine the reduction was either 1.5 or 1.3 days, depending on monthly or quarterly dosing. The most common side effect was injection site reactions.

  • Galcanezumab: in two trials involving more than 1700 patients with episodic migraine, patients showed an average reduction in monthly migraine days of 1.9 days (for the lower dose) and 1.8 days (for the higher dose) compared to placebo after 6 months of treatment. The most common side effect was injection site reactions.

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European Medicines Agency (EMA) strengthens measures to avoid use of valproate medicines in pregnancy

In March 2018, the EMA announced stronger measures aimed at avoiding the exposure of babies to valproate medicines in the womb. Under the new restrictions, valproate medicines are contraindicated for migraine prophylaxis during pregnancy due to the high risk of congenital malformations and developmental problems in the child.

In addition, valproate medicines must not be used in female patients of childbearing potential unless there is a pregnancy prevention program in place that includes the following:

  • An assessment of the patient’s potential for becoming pregnant

  • Pregnancy tests before starting (and during) treatment as needed

  • Counseling about the risks of valproate treatment and the need for effective contraception throughout treatment

  • A review of ongoing treatment by a specialist, at least annually

  • A risk acknowledgement form that patients and prescribers can go through at each such annual review to confirm that appropriate advice has been given and understood.

The EMA said the new measures were put in place because of evidence suggesting that information on the risks of valproate use in pregnancy was still not getting through to women, despite earlier steps aimed at ensuring this.

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Original source of update

Summary

Definition

History and exam

Key diagnostic factors

  • prolonged headache
  • nausea
  • decreased ability to function
  • headache worse with activity
  • sensitivity to light
  • sensitivity to noise
  • aura

Other diagnostic factors

  • vomiting
  • unilateral
  • throbbing sensation

Risk factors

  • family history of migraine
  • high caffeine intake
  • exposure to change in barometric pressure
  • female sex
  • obesity
  • habitual snoring
  • stressful life events
  • overuse of headache medications
  • lack of sleep
  • low socioeconomic status
  • allergies or asthma
  • hypertension
  • hypothyroidism
  • diet

Diagnostic investigations

Investigations to consider

  • erythrocyte sedimentation rate (ESR)
  • lumbar puncture (LP)
  • cerebrospinal fluid (CSF) culture
  • CT head
  • MRI brain
Full details

Treatment algorithm

Contributors

Authors VIEW ALL

Associate Professor of Neurology

Chief

Headache Division

Department of Neurology

Duke University Medical Center

Durham

NC

Disclosures

TAC was an unpaid site PI for the Alder study ALD403-CLIN-011 (monoclonal Ab against CGRP as treatment for chronic migraine), which ended in July 2017. TAC served as a paid consultant for Eli Lilly Co. in November 2016. In 2017 he served as a paid consultant for Alphasights, a global healthcare consulting organization, regarding migraine headache diagnosis and treatment. He has provided expert testimony regarding headache disorders for a legal case in 2015, and expects to be paid to provide expert testimony on headache disorders in 2018 for a legal case relating to the diagnosis, treatment, and standard of care for headache disorders.

Dr Timothy Collins would like to gratefully acknowledge Dr Ann Donnelly, the previous contributor to this monograph. AD declares that she has no competing interests.

Peer reviewers VIEW ALL

Professor

Family and Community Medicine

University of Kansas School of Medicine

Wichita

KS

Disclosures

AW declares that she has no competing interests.

Director

Walton Headache Center

Augusta

GA

Disclosures

MSH declares that he has no competing interests.

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