In an adult (≥18 years) with episodic migraine (≥4 migraine days/month) or chronic migraine (≥15 headache days/month, ≥8 migraine days) who has failed at least two approved preventive therapies, what are the indications and criteria for prescribing Ajovy (fremanezumab) for migraine prophylaxis?

Indications and Criteria for Ajovy (Fremanezumab) for Migraine Prophylaxis

Ajovy (fremanezumab) is strongly recommended for the preventive treatment of both episodic migraine (≥4 migraine days/month) and chronic migraine (≥15 headache days/month with ≥8 migraine days) in adults, and can be initiated as a first-line preventive therapy without requiring prior treatment failures. 1

Primary Indications

FDA-Approved Indications

• Preventive treatment of migraine in adults (no restriction to specific migraine subtypes or requirement for prior treatment failures) 2
• Preventive treatment of episodic migraine in pediatric patients aged 6-17 years weighing ≥45 kg 3

Clinical Definitions

• Episodic migraine: 1-14 headache days per month, with at least 4 migraine days per month 1
• Chronic migraine: ≥15 headache days per month for >3 months, with ≥8 days meeting migraine criteria 4, 5

Evidence-Based Recommendations

Guideline Support

The 2024 VA/DoD guidelines provide a strong recommendation (highest level) for fremanezumab, alongside erenumab and galcanezumab, for prevention of both episodic and chronic migraine. 1

The 2025 American College of Physicians guidelines include fremanezumab among CGRP monoclonal antibodies as a conditional recommendation for episodic migraine prevention, though they suggest considering it after initial trials of other preventive medications due to cost considerations. 1

Dosing Regimens

Available Options

Two FDA-approved subcutaneous dosing schedules: 2

• Monthly dosing: 225 mg every month
• Quarterly dosing: 675 mg every 3 months (administered as three consecutive 225 mg injections)

Administration Details

• Subcutaneous injection in abdomen, thigh, or upper arm 2
• Available as prefilled autoinjector or prefilled syringe 2

Clinical Efficacy Data

Chronic Migraine

In chronic migraine patients, fremanezumab reduced monthly headache days by 4.3 days (quarterly dosing) and 4.6 days (monthly dosing) compared to 2.5 days with placebo over 12 weeks. 5

• 38-41% of patients achieved ≥50% reduction in monthly headache days versus 18% with placebo 5

Episodic Migraine

In episodic migraine patients, fremanezumab reduced monthly migraine days by 1.3-1.5 days compared to placebo over 12 weeks. 6

Difficult-to-Treat Populations

Real-world data demonstrate effectiveness in challenging subgroups: 7

• Medication overuse: 80.6% reduction in monthly migraine days at 6 months
• Major depressive disorder: 68.3% reduction
• Generalized anxiety disorder: 66.4% reduction
• Prior CGRP monoclonal antibody exposure: 68.7% reduction

When to Initiate Fremanezumab

First-Line Consideration

Fremanezumab can be initiated as first-line preventive therapy without requiring prior treatment failures, particularly when: 1

• Patient has significant migraine-related disability affecting quality of life
• Contraindications exist to traditional preventive medications (e.g., topiramate in women of childbearing potential, beta-blockers in asthma)
• Patient preference for injectable therapy with less frequent dosing

After Other Preventive Failures

The ACP guidelines suggest considering CGRP monoclonal antibodies when patients do not tolerate or have inadequate response to: 1

• Beta-blockers (propranolol, metoprolol)
• Antiseizure medications (topiramate, valproate)
• Angiotensin II-receptor blockers (candesartan, telmisartan)
• Tricyclic antidepressants (amitriptyline)

Chronic Migraine Specific

For chronic migraine, fremanezumab is appropriate when: 1

• Patient meets criteria for chronic migraine (≥15 headache days/month, ≥8 migraine days)
• Topiramate has been tried (the only oral medication with proven efficacy in chronic migraine) 1
• OnabotulinumtoxinA is not tolerated, contraindicated, or ineffective 1

Contraindications

The only absolute contraindication is serious hypersensitivity to fremanezumab or any excipients. 2

Common Pitfalls to Avoid

Diagnostic Accuracy

• Ensure accurate diagnosis: Patients must truly have ≥15 headache days/month for chronic migraine diagnosis, not just reporting their "severe headache days" while omitting milder ones 1
• Use headache diaries: Ask patients to track headaches prospectively rather than relying on recall 1

Treatment Expectations

• Injection site reactions are the most common adverse event (≥5%) but rarely lead to discontinuation 2, 5
• Hepatic function abnormalities occurred in 1% of patients in clinical trials 5
• Effectiveness may be seen as early as the first month but assess response over at least 3 months 7

Medication Overuse Consideration

Fremanezumab remains effective even in patients with medication overuse headache, demonstrating 80.6% reduction in monthly migraine days at 6 months in real-world settings. 7 This should not delay initiation, though concurrent management of medication overuse is still recommended. 1

Dose Escalation Considerations

For patients with partial response to standard dosing, the 300mg dose of eptinezumab (a different CGRP monoclonal antibody) shows greater efficacy than 100mg. 8 While this specific data is for eptinezumab, the principle of dose optimization applies across CGRP monoclonal antibodies when initial response is inadequate.