Eptinezumab Medical Necessity Assessment per MCG A-1032 Criteria
Direct Answer
Eptinezumab is medically indicated for migraine prevention when patients have failed or inadequately responded to first-line preventive therapies (beta-blockers, valproate, venlafaxine, or amitriptyline), as it is positioned as second-line therapy in current clinical guidelines. 1
MCG Criteria Alignment
The American College of Physicians 2025 guideline explicitly positions eptinezumab as second-line monotherapy for episodic migraine prevention, specifically recommending CGRP monoclonal antibodies (including eptinezumab) only after patients "do not tolerate or inadequately respond to a trial or trials" of first-line agents 1. This hierarchical approach aligns with standard utilization management criteria requiring documented failure of conventional therapies before approval of biologics.
Required Documentation for Medical Necessity:
- Confirmed migraine diagnosis with 4-15 migraine days per month (episodic) or ≥15 headache days per month with ≥8 migraine days (chronic) per International Headache Society criteria 2, 3
- Documented trials and failures of at least one first-line preventive: metoprolol, propranolol, valproate, venlafaxine, or amitriptyline 1
- Adequate trial duration of 8-12 weeks at therapeutic doses for each failed preventive 1, 4
- Baseline migraine frequency documented via headache diary for minimum 28 days 2
Dosing and Administration Requirements
The FDA-approved dosing is 100 mg IV every 12 weeks, with option to escalate to 300 mg IV every 12 weeks for patients who may benefit from higher dosing 2.
Critical consideration: Starting directly at 300 mg without trialing 100 mg first typically requires additional justification demonstrating severe disease burden (≥15 migraine days/month, multiple prior preventive failures, or significant functional impairment) 4, 2.
Infrastructure Requirements:
- IV infusion capability over 30 minutes 2
- Post-infusion monitoring for hypersensitivity reactions (most common adverse event at 2.1%) 2, 5
- Patient time commitment of approximately 1-2 hours per quarterly visit 4
Efficacy Benchmarks for Continuation
Continuation criteria require demonstrable response after 3 months (first dose): minimum 30% reduction in monthly migraine days from baseline, though ≥50% response is the standard efficacy threshold used in clinical trials 4, 2, 3.
The DELIVER trial demonstrated that among initial non-responders during weeks 1-12,30.4% became responders after the second infusion at week 12, supporting continuation through at least two doses (24 weeks) before declaring treatment failure 4, 3.
Response Assessment Timeline:
- Week 4: Early response assessment (efficacy evident from day 1 in clinical trials) 5, 6
- Week 12: Primary efficacy endpoint - require ≥30% reduction in MMDs for continuation 4, 2
- Week 24: Secondary assessment after second dose - consider discontinuation if <30% response 4, 3
Special Populations and Contraindications
Relative contraindications requiring careful consideration:
- Recent cardiovascular or cerebrovascular ischemic events (within 12 months) - eptinezumab should be used with caution 4
- Pregnancy or women of childbearing potential not using contraception - limited safety data, though no adverse developmental effects in animal studies at 30× human dose 2
- Patients requiring immediate migraine control - IV administration during acute attack showed efficacy but feasibility in routine practice remains uncertain 5
Common Pitfalls in Prior Authorization
Frequent denial reasons and how to address them:
Insufficient documentation of first-line failures: Must document specific medications tried, doses achieved, duration of trial (8-12 weeks minimum), and reason for discontinuation (inefficacy vs. intolerance) 1, 4
Medication overuse headache not addressed: Patients using acute medications ≥10 days/month (triptans/combination analgesics) or ≥15 days/month (simple analgesics) may have reduced preventive efficacy and require medication withdrawal first 4, 7
Requesting 300 mg initial dose without justification: Document chronic migraine (≥15 headache days/month), ≥2 prior preventive failures, or severe functional impairment to support higher initial dosing 4, 2
Inadequate baseline documentation: Require prospective 28-day headache diary documenting frequency, duration, and associated symptoms before treatment initiation 2
Evidence Quality Considerations
The 2025 American College of Physicians guideline provides conditional recommendation with low-certainty evidence for eptinezumab, reflecting that while efficacy is demonstrated, the evidence does not clearly favor CGRP antibodies over first-line agents when considering cost and route of administration 1. The DELIVER trial specifically studied patients with 2-4 prior preventive failures and demonstrated significant efficacy (mean reduction 4.8-5.3 MMDs vs. 2.1 with placebo, p<0.0001), supporting use in treatment-refractory populations 3.