Migraine prevention can be particularly challenging in patients with frequent migraine days, medication overuse, and multiple previous preventive treatment failures. Although randomized trials have established the efficacy and safety of calcitonin gene-related peptide (CGRP)-targeted therapies, prospective long-term data from routine clinical practice remain limited, particularly among patients who have not previously received a CGRP monoclonal antibody. Eptinezumab is an intravenously administered monoclonal antibody that binds CGRP and is given every 12 weeks. This study evaluated its effectiveness and safety over 12 months in a difficult-to-treat, CGRP monoclonal antibody-naïve population.
This prospective, single-center observational study included 302 adults enrolled in the French FHU InovPain registry between June 2023 and September 2025. Eligible patients had at least 8 monthly migraine days and had experienced failure, intolerance, or contraindication to at least 3 preventive treatments among amitriptyline, beta-blockers, onabotulinumtoxinA, candesartan, and topiramate. All participants received intravenous eptinezumab 100 mg every 12 weeks. Dose escalation to 300 mg was not available because of institutional financial constraints. Outcomes were assessed at months 3, 6, and 12 using headache diaries, responder rates, patient-reported measures, and adverse-event monitoring.
The study population had substantial baseline disease burden. The mean age was 48.0 years, 83.8% of participants were women, and 60.9% had chronic migraine. Mean monthly migraine days were 17.0, and 75.8% of patients had medication overuse. More than one-third reported continuous headache pain, and baseline scores indicated severe headache-related functional impact and considerable interictal and emotional burden. All 302 participants were evaluable at month 3, while 246 and 138 were evaluable at months 6 and 12, respectively.
The primary outcome, a reduction of at least 50% in monthly migraine days, was achieved by 35.4% of patients at month 3, 39.1% at month 6, and 45.7% at month 12. At the same time points, at least 30% reductions were observed in 48.7%, 56.1%, and 63.0% of patients, while at least 75% reductions occurred in 10.9%, 15.4%, and 23.2%. Mean monthly migraine days decreased from 17.0 at baseline to 12.5 at month 3, 11.4 at month 6, and 9.2 at month 12. Monthly headache days and days of acute migraine medication use also declined significantly at every assessment.
Responder rates (≥30%, ≥50%, and ≥75% reduction from baseline in monthly migraine days)
| Time point |
≥30% response |
≥50% response |
≥75% response |
| M3 (n=302) |
48.7% |
35.4% |
10.9% |
| M6 (n=246) |
56.1% |
39.1% |
15.4% |
| M12 (n=138) |
63.0% |
45.7% |
23.2% |
Improvements extended beyond headache frequency. Scores measuring headache-related impact, anxiety and depressive symptoms, interictal burden, and health-related quality of life all improved significantly from baseline. The proportion of patients rating themselves as “much improved” or “very much improved” increased from 41.9% at month 3 to 74.4% at month 12. Medication overuse declined from 75.8% at baseline to 31.6% at month 12. Among patients with chronic migraine at baseline, 47.3% met criteria for episodic migraine at month 3, increasing to 68.8% among those evaluated at month 12.
Observed-case responder rates appeared to increase over time, but these findings should be interpreted cautiously because fewer than half of the original cohort remained evaluable at month 12 and ineffectiveness was a major reason for discontinuation. In a last-observation-carried-forward sensitivity analysis including all 302 participants, 50% responder rates were 35.4% at month 3, 36.1% at month 6, and 36.8% at month 12. This analysis still supported sustained improvement but suggested that the observed-case results may overestimate longer-term effectiveness.
Adverse events were uncommon and generally mild and transient. Nonallergic events included asthenia, nausea, scalp pruritus, transient cognitive fog, paresthesia, and alopecia, each occurring in approximately 1% or fewer of patients. Six patients experienced hypersensitivity reactions, including bronchospasm, rash, or urticaria. One case of severe generalized urticaria resulted in treatment discontinuation, while two other severe reactions were managed using a desensitization protocol that permitted continued treatment.
In this prospective real-world cohort, quarterly eptinezumab 100 mg was associated with clinically meaningful reductions in migraine frequency, acute medication use, medication overuse, and patient-reported burden among patients with severe, difficult-to-treat migraine who were naïve to CGRP monoclonal antibodies. The results support eptinezumab as an effective and generally well-tolerated preventive option, while also emphasizing the need to account for attrition and treatment discontinuation when interpreting long-term real-world response rates.