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CGRP-targeting therapies as first-line option for migraine prevention

By Priscilla Lynch - 01st Jan 2025

migraine-prevention

Reference: January 2025 | Issue 1 | Vol 11 | Page 34


American Headache Society position statement on the first-line use of CGRP-targeting migraine prevention therapies

Last year, the American Headache Society (AHS) issued a position statement update on the use of migraine prevention therapies targeting calcitonin gene-related peptide (CGRP).1

The paper says that CGRP-targeting therapies should be considered as a first-line approach for migraine prevention along with previous first-line treatments, without a requirement for prior failure of other classes of migraine preventive treatment.

Commenting on the rationale behind the new consensus statement, the President of the American Headache Society Dr Andrew Charles, Professor and Director of the Headache Research and Treatment Program at UCLA School of Medicine, said the creation of the new guideline was driven by the recent “astonishing” surge in both clinical trial and real-world evidence on the use of CGRP agents in the prevention of migraine. “The evidence for their efficacy and especially their tolerability is just so overwhelming and our clinical experience backs that up,” he said.

“I would also point out that what comes out of some of the formal clinical trials and also some of the real world evidence is that these therapies work even in patients who’ve tried a host of other preventive therapies and failed to continue them either due to lack of efficacy or tolerability, so that’s very important.”

Guideline development

The AHS Board of Directors recognised the need for this specific guidance based on the pre-specified criteria in prior AHS consensus statements for iterative updates addressing the integration of newer migraine treatments. After a series of discussions over 2022 to 2023, a taskforce was established.

This taskforce reviewed data on the efficacy, safety, and use of migraine treatments since the previous AHS consensus statement was undertaken.

Evidence regarding migraine preventive was collected from a variety of sources including primary and secondary endpoints from randomised placebo-controlled clinical trials, post hoc analyses, as well as open-label extensions of these trials, and prospective and retrospective observational studies. The results and conclusions based on these results were reviewed and discussed by the Board of Directors of the AHS to confirm consistency with clinical experience and to achieve consensus.

A. Treatments to consider for episodic migraine with or without aura (4–14 MMDs) based on ICHD-3 with at least moderate disability (MIDAS score ≥11 or HIT-6 score ≥50)
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 American Academy of Neurology (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
B. Treatments to consider for chronic migraine with or without aura (≥15 MHDs) based upon ICHD-3
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 and rimegepant

TABLE 1: AHS updated recommendations for migraine prevention

Results

The evidence for the efficacy, tolerability, and safety of CGRP-targeting migraine preventive therapies (the monoclonal antibodies: erenumab, fremanezumab, galcanezumab, and eptinezumab, and the gepants: rimegepant and atogepant) is substantial, and vastly exceeds that for any other preventive treatment approach, the AHS said.

Previous AHS consensus statements have summarised evidence from pivotal clinical trials of CGRP-targeting preventive therapies, which have all shown statistically significant improvement in migraine (or headache) days, for both episodic and chronic migraine, with nearly all agents.

The evidence remains consistent across different individual CGRP-targeting treatments and is corroborated by extensive real-world clinical experience. Real world studies have generally confirmed the results of the randomised controlled trials (RCTs) regarding efficacy, tolerability, and safety, and they do so within a wide variety of international cohorts, often over long time periods, the AHS noted.

Overall, the data indicates that the efficacy and tolerability of CGRP-targeting therapies are equal to or greater than those of previous first-line therapies and that serious adverse events associated with CGRP-targeting therapies are rare.

“Based on this evidence and extensive clinical experience, CGRP-targeting therapies have rapidly become an indispensable option for the prevention of migraine,” the statement document says.

A consistent finding across all the studies of CGRP-targeting therapies for migraine prevention has been a very low drop-out rate, the AHS statement document says. “This finding is an indicator of adherence, which in turn is an indicator of both efficacy and tolerability.”

Cost and access

The AHS acknowledges that the cost of, and therefore access to, these preventive therapies is an important factor (costs vary across health systems), but adds that this needs to be weighed alongside the cost of acute treatment, and the economic and personal cost of migraine (lost education, productivity, income, and interpersonal relationships).

“It is clear that if cost were not a primary consideration, there would be no controversy regarding the legitimate place for CGRP-targeting therapies as a first-line option for migraine prevention given their established safety, efficacy, and years of integration into practice.”

European position

As noted by the AHS in its position statement, in 2022 the European Headache Federation issued a guideline update² recommending the use of monoclonal antibodies targeting the CGRP pathway for migraine prevention. It stated “the available data confirm that monoclonal antibodies targeting the CGRP pathway appear to be effective and safe for migraine prevention even in the long-term.

Objective biomarkers of treatment response are still lacking; nevertheless, the available RCTs and real-world data can provide insights on treatment individualisation, including treatment duration, combination with other treatments, and the management of safety issues.”

References

  1. 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 Apr;64(4):333-341.
  2. Sacco S, Amin FM, Ashina M, et al. European Headache Federation guideline on the use of monoclonal antibodies targeting the calcitonin gene-related peptide pathway for migraine prevention – 2022 update. J Headache Pain. 2022 Jun 11;23(1):67.

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