Is there a superior migraine prevention treatment between Ajovy (fremanezumab), Aimovig (erenumab), and Emgality (galcanezumab) for patients with frequent and severe migraines?

Comparative Efficacy of CGRP Monoclonal Antibodies for Migraine Prevention

No CGRP monoclonal antibody (Ajovy/fremanezumab, Aimovig/erenumab, or Emgality/galcanezumab) demonstrates superior efficacy over the others—all three reduce migraine frequency by approximately 3.4-4.7 days per month with similar tolerability profiles, and none should be used as first-line therapy. 1, 2

Treatment Algorithm: When to Use Each Agent

Start with conventional preventives first (metoprolol, propranolol, valproate, venlafaxine, or amitriptyline) before considering any CGRP-mAb, driven primarily by the 100-fold cost difference ($67-$393 annually vs. $7,071-$22,790) rather than efficacy differences. 1

First-Line Therapy (Use Before Any CGRP-mAb)

• Beta-blockers: Propranolol 80-240 mg daily or metoprolol 1, 3
• Antidepressants: Amitriptyline or venlafaxine 1
• Antiseizure: Valproate 1

Second-Line: CGRP Monoclonal Antibodies (After First-Line Failure)

When conventional preventives fail or are not tolerated, all three CGRP-mAbs are equivalent options: 1, 2

Fremanezumab (Ajovy):

• Dosing flexibility: 225 mg monthly OR 675 mg quarterly 4
• Reduces migraine days by 3.4-3.7 days/month vs. placebo 4
• Cardiovascular advantage: No association with hypertension development, unlike erenumab 2
• 47.7% achieve ≥50% reduction in migraine days 4

Galcanezumab (Emgality):

• 240 mg loading dose, then 120 mg monthly 5
• Reduces migraine days by 4.3-4.7 days/month vs. placebo 5
• 59-62% achieve ≥50% reduction in migraine days 5
• No additional benefit from 240 mg monthly dose over 120 mg 5

Erenumab (Aimovig):

• 70 mg or 140 mg monthly 2
• Similar efficacy to fremanezumab and galcanezumab 2, 6
• Critical pitfall: Post-marketing reports show risk of developing or worsening hypertension 2

Third-Line: Topiramate

Use only after both conventional preventives AND CGRP-mAbs fail, as topiramate has higher adverse event rates (162 more discontinuations per 1000 patients) despite similar efficacy. 1

Choosing Between the Three CGRP-mAbs

Since direct comparative evidence shows no superiority of one over another, selection depends on: 2

Choose Fremanezumab (Ajovy) if:

• Patient has cardiovascular concerns (hypertension, coronary disease) 2
• Quarterly dosing preferred (reduces injection frequency) 4
• Patient wants flexibility between monthly/quarterly administration 4

Choose Galcanezumab (Emgality) if:

• Standard monthly dosing acceptable 5
• Patient responds well to loading dose strategy 5

Avoid Erenumab (Aimovig) if:

• Patient has uncontrolled hypertension or cardiovascular risk factors 2
• Patient develops hypertension during treatment 2

Network Meta-Analysis Evidence

Fremanezumab 225 mg and 675 mg demonstrated statistical superiority over lower-dose erenumab (21 mg, 70 mg) in reducing monthly migraine days, but no clinically meaningful differences exist between standard therapeutic doses of the three agents. 6 Galcanezumab 120 mg and fremanezumab 225 mg may represent optimal dosing after comprehensive assessment. 6

Efficacy Timeline and Discontinuation Strategy

• Assess response at 3-6 months: Responder rates improve from 44% at 3 months to 64% at 12 months 7
• Consider treatment pause after 6-12 months of success to determine if preventive therapy can be discontinued 2
• 12-month adherence: Approximately 55% for CGRP-mAbs vs. 35% for oral preventives 7

Common Adverse Events (Similar Across All Three)

• Injection-site pain and upper respiratory tract infections (most common) 2
• Constipation (relative risk 1.32-1.55 vs. placebo) 7
• Discontinuation due to adverse events: 5.9-20% 7
• Serious adverse events: <5% 7

Critical Cost Consideration

All three CGRP-mAbs have intermediate-to-low value compared to no preventive treatment, with annual costs of $7,071-$22,790 versus $67-$393 for conventional preventives. 1 This cost differential, not efficacy differences, drives the recommendation to use conventional preventives first. 1

Medication Overuse Headache

All three CGRP-mAbs effectively reduce medication overuse headache without requiring drug withdrawal: 80% of patients achieve ≥50% reduction in both monthly headache days and analgesic intake at 3 months. 8