Calcitonin Gene-Related Peptide Inhibitors - Use in Chronic Migraine, Neurology (691)


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A guideline is intended to assist healthcare professionals in the choice of disease-specific treatments.

Clinical judgement should be exercised on the applicability of any guideline, influenced by individual patient characteristics. Clinicians should be mindful of the potential for harmful polypharmacy and increased susceptibility to adverse drug reactions in patients with multiple morbidities or frailty.

If, after discussion with the patient or carer, there are good reasons for not following a guideline, it is good practice to record these and communicate them to others involved in the care of the patient.


Erenumab (Aimovig®), Fremanezumab (Ajovy®) and Galcanezumab (Emgality®) are calcitonin gene-related peptide (CGRP) inhibitors which are indicated for the prophylaxis of chronic migraine in adults. CGRP is associated with vasodilation, inflammation and modulation of the transmission of pain. Levels of CGRP increase significantly during migraine and return to baseline levels with headache relief.

Agent and route

Subcutaneous solution for injection in pre-filled pen or pre-filled syringe

Patient population applicable to:

In line with the Scottish Headache Interest Group, experts in NHS GGC propose that CGRP inhibitors should be restricted to specialist use in patients with chronic migraine (i.e. headaches occurring on 15 or more days per month of which ≥ 8 are migraine days) for whom at least four prior prophylactics (+/- flunarizine) have failed and the patient has failed to respond to, or not tolerated, an adequate trial of botulinum toxin A (Botox®). CGRP inhibitors may be considered if Botox® is contraindicated.

Authorised and Designated Areas applicable to

Homecare prescription will be initiated by a Headache Specialist Nurse/ GPSI/ Consultant/ Pharmacist. Products require storage in a refrigerator and Homecare Company will supply sharps box.

The patient’s General Practioner will be informed that this medicine is being prescribed and supplied to the patient via home delivery services. Within General Practice it is beneficial for patient and prescriber safety to ensure that a patient’s medicine record includes medicines that may be prescribed and supplied outwith the GP practice.

Indication and place in therapy

CGRP inhibitors should only be considered once patient has received an adequate trial (>6 weeks at therapeutic dose unless side effects or contraindicated) of the following medicines:
• Beta blockers (e.g. propranolol)
• Topiramate
• Tricyclic antidepressant drug (e.g. amitriptyline)
• Candesartan
• Botulinum toxin A (Botox®)
• +/- Flunarizine

Medication overuse must be addressed prior to initiating CGRP inhibitors.

Cost-effectiveness should be considered when choosing a first line CGRP inhibitor. Erenumab (Aimovig®) contains latex in the needle cap and should be avoided in patients with a latex allergy.

First line therapy
Erenumab or Galcanezumab should be considered as first line CGRP inhibitor. Galcanezumab should be used if patient is allergic to latex.

Second line therapy
Erenumab or Galcanezumab should be considered if patient fails to respond to first line therapy. Fremanezumab can be used as second line therapy if patient is allergic to latex.

Third line therapy
Fremanezumab can be considered if patient fails to respond to first and second line therapies.

Clinical studies have demonstrated that the majority of patients responding to therapy showed clinical benefit within 3 months. Patients who do not respond to treatment will discontinue after 12 weeks. It is estimated that between 40-60% of patients will be non-responders at the 12 week assessment. Patients must complete headache diaries and bring these to their appointment.

Dose, duration and administration

140mg every 4 weeks

240mg loading dose followed by 120mg once monthly

Two dosing options are available:
• 225mg once monthly (monthly dosing) or
• 675mg every three months (quarterly dosing)


Patients will be reviewed in clinic prior to commencing treatment and after a 3 month trial to assess for efficacy and side effects.

A positive response is defined as either a:
• 30% reduction in the number of headache days based on analysis of baseline headache diaries
• 50% reduction in migraine days (i.e. severe headaches which are at least 7/10 in severity)

Following a positive response, treatment will be continued for a further 9 months until patient has received treatment for up to 1 year. Patient will have a 3-month treatment break and then be reviewed by their Consultant or GPSI. If patient reverts to chronic migraine, the CGRP inhibitor may be re-started or an alternative therapy commenced.

A treatment holiday will be considered if chronic migraine becomes episodic (i.e. <15 days/month with headache for 3 consecutive months).

Treatment will be stopped if:
• Treatment has failed to reduce the number of headache days by at least 30% or severe headache days reduce by at least 50%
• Patient becomes pregnant or is breast feeding.
• Patient becomes refractory to treatment (headache days per month rise to comparable levels pre-CGRP inhibitor)

In line with expert opinion, a treatment break of 3 months is recommended before switching from one CGRP inhibitor to another.

Strength of preparation used

Erenumab 140mg s/c injection (Auto-injector)

Fremanezumab 225mg s/c injection (Auto-injector)

Galcanezumab 120mg s/c injection (Auto-injector)

Licensed status

Licensed Medicine

Authorised prescribers

Consultant Neurologists with Specialist Interest in Headache
Designated General Practitioners with Specialist Interest in Headache
Designated non-medical prescribers (e.g. Clinical Nurse Specialists, Specialist Pharmacists)

Authorised for administration

Patient will be educated and trained on injection technique at initial clinic appointment.

Authorised for storage in clinical areas

Yes. Store in a refrigerator

Endorsed by

NHS GGC Headache Team

Last reviewed: 07 July 2021

Next review: 25 July 2024

Author(s): Lesley Murray

Version: 4

Author Email(s): [email protected]

Approved By: Medicines Utilisation Subcommittee of ADTC

Document Id: 691