CGRP Inhibitors for Migraine Treatment
CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, and eptinezumab) should be used as third-line preventive treatments for migraine after failure of at least two first-line medications. 1
Treatment Algorithm for Migraine Prevention
First-Line Options
- Beta blockers without intrinsic sympathomimetic activity (atenolol, bisoprolol, metoprolol, propranolol)
- Topiramate
- Candesartan
Second-Line Options
- Flunarizine
- Amitriptyline
- Sodium valproate (contraindicated in women of childbearing potential)
Third-Line Options (CGRP Pathway Inhibitors)
CGRP monoclonal antibodies:
- Erenumab (Aimovig): CGRP receptor antagonist, subcutaneous injection
- Fremanezumab (Ajovy): CGRP antagonist, subcutaneous injection
- Galcanezumab (Emgality): CGRP antagonist, subcutaneous injection
- Eptinezumab: CGRP antagonist, intravenous infusion
CGRP antagonists-gepants:
- Atogepant: oral, preventive
- Rimegepant: oral, preventive
Efficacy and Assessment
- CGRP inhibitors reduce migraine frequency by at least 50% in 50-60% of patients 2
- Efficacy should be assessed only after 3-6 months of treatment 1, 3
- Consider discontinuing after 6-12 months of successful therapy to evaluate continued need 1, 3
Indications for CGRP Inhibitors
- Adults with episodic or chronic migraine
- Patients who have failed at least two conventional preventive treatments
- Patients with at least 8 migraine days per month 2
- Particularly effective in patients with medication overuse headache (80% response rate) 4
Advantages of CGRP Inhibitors
- Better tolerability profile compared to conventional oral preventives 2
- Lower discontinuation rates due to adverse effects compared to topiramate 1
- May reduce both migraine frequency and acute medication use more effectively than topiramate 1
- Effective even in patients who have failed multiple conventional preventives 2
Important Considerations and Limitations
Administration Routes
- Erenumab, fremanezumab, galcanezumab: subcutaneous injection (monthly or quarterly)
- Eptinezumab: intravenous infusion (quarterly)
- Patients generally prefer oral treatments over injectables 1
Cost Considerations
- CGRP inhibitors are significantly more expensive than traditional preventives
- Annual costs range from $7,071 to $22,790 compared to $67-$393 for first-line options 1, 3
Contraindications
- History of cardiovascular disease 3, 2
- CGRP inhibitors may inhibit vasodilation, posing risk in cardiovascular patients 2
Special Population: Non-responders
- If a patient doesn't respond to one CGRP inhibitor class, switching to another class may be beneficial
- Approximately 32% of erenumab non-responders may benefit from switching to a CGRP-mAb (galcanezumab or fremanezumab) 5
- Switching appears more effective in patients with non-daily headache compared to those with daily headache 5
Clinical Pearls
- Always optimize acute treatment before considering preventive therapy
- Consider preventive treatment in patients adversely affected by migraine on ≥2 days per month despite optimized acute treatment 1
- CGRP inhibitors are particularly valuable for patients who cannot tolerate side effects of traditional preventives
- Medication overuse headache should be addressed before or concurrently with preventive treatment 1
- Recognize and modify risk factors for transformation from episodic to chronic migraine (female sex, high headache frequency, inadequate treatment, medication overuse, depression, anxiety, obesity) 1
CGRP inhibitors represent a significant advance in migraine-specific preventive treatment, offering hope to patients who have not responded to conventional therapies, though their use is currently limited by cost and regulatory restrictions in many regions.