Treatment of Migraine Using Monoclonal Antibodies
CGRP monoclonal antibodies should be considered as third-line medications for migraine prevention after failure of first-line and second-line treatments. 1
Migraine Prevention Treatment Algorithm
First-Line Treatments
- Beta blockers without intrinsic sympathomimetic activity (atenolol, bisoprolol, metoprolol, or propranolol) 1
- Topiramate 1
- Candesartan 1
Second-Line Treatments
Third-Line Treatments (Monoclonal Antibodies)
- Erenumab (targets CGRP receptor) 1, 2
- Fremanezumab (targets CGRP ligand) 1
- Galcanezumab (targets CGRP ligand) 1, 3
- Eptinezumab (targets CGRP ligand) 1
Indications for CGRP Monoclonal Antibodies
- Consider in patients who have failed or cannot tolerate first-line and second-line preventive medications 1, 2
- Appropriate for patients who are adversely affected by migraine on ≥2 days per month despite optimized acute treatment 1
- In Europe, regulatory restrictions limit use to patients in whom other preventive drugs have failed or are contraindicated 1
- The American College of Physicians recommends these as second-line options when first-line treatments are not tolerated or provide inadequate response 1, 2
Dosing and Administration
Erenumab
- Available in 70 mg and 140 mg monthly subcutaneous doses 2, 4
- Some patients may benefit from the higher 140 mg dose, especially those with difficult-to-treat disease and prior treatment failures 4
- Efficacy should be assessed after 3-6 months of treatment 1, 2
Galcanezumab
- Administered monthly via subcutaneous injection 3
- Monitor for injection site reactions, which occur in approximately 18% of patients 3
Fremanezumab
- Can be administered monthly (225 mg) or quarterly (675 mg) via subcutaneous injection 1
- Not recommended in patients with history of stroke, coronary heart disease, inflammatory bowel disease, or COPD 1
Efficacy and Outcomes
- CGRP monoclonal antibodies have demonstrated efficacy in reducing monthly migraine days in both episodic and chronic migraine 5, 4, 6
- They can be effective in reducing medication overuse headache in chronic migraine patients 7
- In Japanese patients with episodic migraine, erenumab 70 mg showed significant reduction in monthly migraine days compared to placebo 5
- Long-term maintenance of efficacy has been demonstrated in post-hoc analyses 6
Safety Considerations
- Monitor for development or worsening of hypertension, particularly with erenumab 2
- Common adverse events include injection site reactions 3
- For galcanezumab, nasopharyngitis (26.9%), back pain (5.4%), and constipation (4.6%) are commonly reported adverse events 3
- Anti-drug antibodies may develop in some patients (4.8% with galcanezumab), but this generally does not affect efficacy 3
- Overall safety profile is favorable compared to many traditional preventive medications 6
Special Populations
Pregnancy
- CGRP monoclonal antibodies are generally not recommended during pregnancy due to limited safety data 1
- Preferred preventive options during pregnancy (if needed) are propranolol or amitriptyline under specialist supervision 1
Older Adults
- Consider comorbidities and potential adverse effects when prescribing in older patients 1
- Limited specific evidence exists for CGRP monoclonal antibody use in older populations 1
Practical Considerations
- Treatment duration: Consider pausing successful preventive treatment after 6-12 months to assess continued need 1
- Cost may be a significant limitation to access for many patients 6
- Treatment success can be measured by percentage reduction in monthly migraine days or monthly headache days of moderate-to-severe intensity 1
Common Pitfalls to Avoid
- Abandoning treatment too early - efficacy of CGRP monoclonal antibodies should be assessed only after 3-6 months 1
- Failing to consider contraindications - particularly important for fremanezumab in patients with vascular conditions 1
- Not monitoring for hypertension during erenumab treatment 2
- Using in women of childbearing potential without adequate contraception 1