What is the best CGRP inhibitor for migraine prevention?

Best CGRP Inhibitor for Migraine Prevention

For migraine prevention in adults, traditional first-line options (beta-blockers, antiseizure medications, antidepressants) should be tried before CGRP inhibitors due to their established efficacy, safety, and lower cost. 1, 2

First-Line Treatment Options (Try These First)

Before considering CGRP inhibitors, the following medications should be tried first due to their established efficacy, safety profile, and cost-effectiveness:

1. Beta-blockers:

   • Propranolol (80-240 mg/day)
   • Metoprolol (50-200 mg/day)

2. Antiseizure medications:

   • Valproate (500-1500 mg/day)
   • Topiramate (100 mg/day) - consider only if other options fail

3. Antidepressants:

   • Amitriptyline (10-150 mg/day)
   • Venlafaxine (SNRI)

CGRP Inhibitors (Second-Line Options)

If first-line treatments fail or are not tolerated, CGRP pathway inhibitors should be considered. These fall into two categories:

CGRP Monoclonal Antibodies (CGRP-mAbs)

• Erenumab (Aimovig): The only CGRP receptor antagonist antibody

  • Dosage: 70-140 mg subcutaneously once monthly
  • Evidence shows 140 mg may be more effective than 70 mg for difficult-to-treat cases 3
  • First FDA-approved CGRP inhibitor 4

• Other CGRP-mAbs (target the CGRP ligand rather than receptor):

  • Fremanezumab
  • Galcanezumab
  • Eptinezumab (IV administration)

CGRP Antagonists (Gepants)

• Atogepant
• Rimegepant

Decision Algorithm for CGRP Selection

1. If oral administration is preferred:

   • Consider CGRP antagonists (gepants) like atogepant or rimegepant
   • Patient values and preferences favor oral over injectable medications 1

2. If monthly administration is preferred:

   • Consider CGRP-mAbs (erenumab, fremanezumab, galcanezumab)
   • Erenumab may be preferred as it targets the receptor rather than the ligand 5, 6

3. For patients with multiple treatment failures:

   • Erenumab 140 mg shows efficacy in patients who failed 2-4 previous preventives 7
   • 30% of patients achieved ≥50% reduction in monthly migraine days vs 14% with placebo

4. For patients with chronic migraine:

   • Real-world data shows significant reduction in headache days with erenumab 8
   • Mean reduction of 6.5 headache days per month at 6 months

Important Considerations

• Cost: CGRP-mAbs and gepants are substantially more expensive than traditional preventives 1
• Administration: Consider patient preference for oral vs. injectable medications
• Side effects: CGRP inhibitors generally have favorable side effect profiles compared to traditional preventives
• Efficacy: All CGRP inhibitors show similar efficacy in clinical trials
• Wearing-off effect: Some patients report diminishing effect in the week before next dose 8

Monitoring and Expectations

• Evaluate response after 3 months (when serum concentrations reach steady state) 5
• 50% responder rate (≥50% reduction in monthly migraine days) is a common outcome measure
• Consider discontinuation if inadequate response after 3-6 months
• Common side effects include injection site reactions and constipation 8

While CGRP inhibitors represent a significant advance in migraine prevention, their high cost and limited long-term safety data support using them after traditional preventives have failed.