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Migraine headache: When to consider these newer agents

The Journal of Family Practice. 2023 September;72(7):292-303 | doi: 10.12788/jfp.0657
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These agents are as effective as traditional acute and preventive treatments, cause fewer adverse effects, and can simplify regimens.

PRACTICE RECOMMENDATIONS

› Consider small-molecule calcitonin gene-related peptide (CGRP) receptor antagonists (gepants) for acute migraine treatment after treatment failure of at least 2 non-CGRP first-line therapies. A

› Consider anti-CGRP monoclonal antibodies or gepants for migraine prevention if traditional therapies have proven ineffective or are contraindicated or intolerable to the patient. A

› Add an anti-CGRP monoclonal antibody or gepant to existing preventive treatment if the patient continues to experience migraine. B

Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

Preventive therapies

Preventive migraine therapies are used to reduce duration, frequency, and severity of attacks, the need for acute treatment, and overall headache disability.26 Medications typically are chosen based on efficacy, adverse effect profile, and patient comorbidities. Barriers to successful use include poor patient adherence and tolerability, the need for slow dose titration, and long-term use (minimum of 2 months) at maximum tolerated or minimum effective doses. Medications with established efficacy (Level Aa) based on the 2012 guidelines from the American Academy of Neurology (AAN) and the AHS are given in TABLE 5.27-29

Adult migraine prophylaxis with established efficacy

Drugs having received the strongest level of evidence for migraine prevention are metoprolol, propranolol, timolol, topiramate, valproate sodium, divalproex sodium, and onabotulinumtoxinA (Botox), and frovatriptan for menstrual migraine prevention. Because these guidelines were last updated in 2012, they did not cover gepants (which will be discussed shortly). The AHS released a position statement in 2019 supporting the use of anti-CGRP monoclonal antibodies (mAbs) in those who cannot tolerate or have had an inadequate response to a 6-week trial of at least 2 AAN/AHA Level A or Bb treatments.10 No head-to-head trials exist between non-CGRP preventive therapies and the CGRP antagonists.

CGRP-targeted prevention

Four anti-CGRP mAbs and 2 gepants have been approved for migraine prevention in the United States. Differences between products include targets (ligand vs receptor), antibody IgG subtype, bioavailability, route of administration, and frequency of administration.28 As noted in the Phase 3 studies (TABLE 619,30-47), these therapies are highly efficacious, safe, and tolerable.

Gepants. Rimegepant, discussed earlier for migraine treatment, is one of the CGRP receptor antagonists approved for prevention. The other is atogepant (Qulipta), approved only for prevention. Ubrogepant is not approved for prevention.

Anti-CGRP mAb is the only medication class specifically created for migraine prevention.10,26 As already noted, several efficacious non-CGRP treatment options are available for migraine prevention. However, higher doses of those agents, if needed, can lead to intolerable adverse effects for some patients, thereby limiting overall efficacy. ­Anti-CGRP mAbs, a targeted, highly efficacious treatment option, offer efficacy comparable to non-CGRP agents with a more favorable adverse effect profile for those who cannot tolerate or achieve only minimal efficacy with traditional preventive therapies.10

Continue to: The targeted anti-CGRP approach...