Calcitonin Gene-related Peptide-Targeting Therapies for Prevention of Migraine

Publication Date: March 11, 2024
Last Updated: April 19, 2024

Summary of Statements

  • There is solid human evidence that establishes CGRP as a fundamental mechanism of migraine and therefore establishes CGRP-targeting therapies as “migraine-specific” in contrast to all the other established therapies.
  • The cumulative evidence for the efficacy, safety, and tolerability of CGRP-targeting therapies is significantly greater than that for any established migraine preventive therapy. The remarkable tolerability of the CGRP-targeting therapies is a particularly positive feature.
  • Nearly all CGRP-targeting therapies are FDA-approved for the preventive treatment of both episodic and chronic migraine, which simplifies decision-making in patients who may spontaneously transition back and forth between episodic and chronic migraine.
  • There are multiple categories of evidence supporting the use of CGRP-targeting therapies that do not exist for other migraine preventive therapies, including: responder rates, efficacy in patients with multiple prior treatment failures, efficacy in those with acute medication overuse, and those who do and do not have aura.
  • There is one head-to-head study demonstrating the superiority of a CGRP-targeting therapy (erenumab) over an established migraine preventive therapy (topiramate). In addition, multiple studies indicating the efficacy of CGRP-targeting migraine preventive therapies in those who have previously failed multiple other established treatments provide indirect evidence of the superiority of CGRP-targeting therapies for some patients.
  • Acknowledging CGRP-targeting therapies as first-line approaches will increase the likelihood that their efficacy and safety will be more thoroughly evaluated in understudied populations, particularly youth.
  • Cost considerations regarding migraine therapies should include not only the direct cost of the treatments, but also the indirect costs of healthcare utilization and acute therapies, as well as socioeconomic costs for those who are disabled by the disease.

Table 1. Indications for initiation of calcitonin gene-related peptide-targeting therapies for migraine in previous American Headache Society consensus statement

Having trouble viewing table?
  • Use is appropriate when A, B, and either C, D, or E are met:
  • Prescribed by a licensed clinician
  • Patient is at least 18 years of age
  • Diagnosis of ICHD-3 migraine with or without aura (4–7 MMDs) and both of the following:
    • Inability to tolerate (due to side-effects) or inadequate response to an 8-week trial at a dose established to be potentially effective of two or morea of the following:
      • Topiramate
      • Divalproex sodium/valproate sodium
      • Beta-blocker: metoprolol, propranolol, timolol, atenolol, nadolol
      • Tricyclic antidepressant: amitriptyline, nortriptyline
      • Serotonin-norepinephrine reuptake inhibitor: venlafaxine, duloxetine
      • Other Level A or B treatments (established efficacy or probably effective) according to AAN scheme for classification of evidence10
    • At least moderate disability (MIDAS score ≥11 or HIT-6 score >50
  • Diagnosis of ICHD-3 migraine with or without aura (8–14 MMDs) and inability to tolerate (due to side-effects) or inadequate response to an 8-week trial of two or morea of the following:
    • Topiramate
    • Divalproex sodium/valproate sodium
    • Beta-blocker: metoprolol, propranolol, timolol, atenolol, nadolol
    • Tricyclic antidepressant: amitriptyline, nortriptyline
    • Serotonin-norepinephrine reuptake inhibitor: venlafaxine, duloxetine
    • Other Level A or B treatments (established efficacy or probably effective) according to AAN scheme for classification of evidence
  • Diagnosis of ICHD-3 chronic migraine and EITHER a or b:
    • Inability to tolerate (due to side-effects) or inadequate response to an 8-week trial of two or morea of the following:
      • Topiramate
      • Divalproex sodium/valproate sodium
      • Beta-blocker: metoprolol, propranolol, timolol, atenolol, nadolol
      • Tricyclic antidepressant: amitriptyline, nortriptyline
      • Serotonin-norepinephrine reuptake inhibitor: venlafaxine, duloxetine
      • Other Level A or B treatments (established efficacy or probably effective) according to AAN scheme for classification of evidence
  • Inability to tolerate or inadequate response to a minimum of two quarterly injections (6 months) of onabotulinumtoxinA

Table 2. Updated recommendations for migraine prevention

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  • Diagnosis of episodic migraine with or without aura (4–14 MMDs) based upon ICHD-3 with at least moderate disability (MIDAS score ≥11 or HIT-6 score >50). Treatments to consider include:
    1. Topiramate
    2. Divalproex sodium/valproate sodium
    3. Beta-blocker: metoprolol, propranolol, timolol, atenolol, nadolol
    4. Candesartan
    5. Tricyclic antidepressant: amitriptyline, nortriptyline
    6. Serotonin-norepinephrine reuptake inhibitor: venlafaxine, duloxetine
    7. Other Level A or B treatments (established efficacy or probably effective) according to AAN scheme for classification of evidence
    8. Monoclonal antibodies targeting CGRP or its receptor including erenumab, fremenezumab, galcanezumab, or eptinezumab
    9. Small-molecules targeting the CGRP receptor (“gepants”) including atogepant and rimegepant
  • Diagnosis of chronic migraine with or without aura (≥15 MHDs) based upon ICHD-3. Treatments to consider include:
    1. Topiramate
    2. Divalproex sodium/valproate sodium
    3. Beta-blocker: metoprolol, propranolol, timolol, atenolol, nadolol
    4. Candesartan
    5. Tricyclic antidepressant: amitriptyline, nortriptyline
    6. Serotonin-norepinephrine reuptake inhibitor: venlafaxine, duloxetine
    7. Other Level A or B treatments (established efficacy or probably effective) according to AAN scheme for classification of evidence
    8. OnabotulinumtoxinA
    9. Monoclonal antibodies targeting CGRP or its receptor including erenumab, fremenezumab, galcanezumab, or eptinezumab
    10. Small-molecules targeting the CGRP receptor (“gepants”) including atogepant

Recommendation Grading

Abbreviations

  • AHS: American Headache Society
  • CGRP: Calcitonin Gene-related Peptide Receptor
  • mAbs: Monoclonal Antibodies

Disclaimer

The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.

Overview

Title

Calcitonin Gene-related Peptide-Targeting Therapies for Prevention of Migraine

Authoring Organization

American Headache Society

Publication Month/Year

March 11, 2024

Last Updated Month/Year

April 19, 2024

Document Type

Consensus

Country of Publication

US

Document Objectives

To provide a position statement update from The American Headache Society specifically regarding therapies targeting calcitonin gene-related peptide (CGRP) for the prevention of migraine. The CGRP-targeting migraine therapies are a first-line option for migraine prevention. Initiation of these therapies should not require trial and failure of non-specific migraine preventive medication approaches.

Inclusion Criteria

Male, Female, Adult, Older adult

Health Care Settings

Ambulatory

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Management

Diseases/Conditions (MeSH)

D008881 - Migraine Disorders

Keywords

migraine, CGRP

Source Citation

Charles AC, Digre KB, Goadsby PJ, Robbins MS, Hershey A; American Headache Society. Calcitonin gene-related peptide-targeting therapies are a first-line option for the prevention of migraine: An American Headache Society position statement update. Headache. 2024 Mar 11. doi: 10.1111/head.14692. Epub ahead of print. PMID: 38466028.