Effects of Intravenous Eptinezumab vs Placebo on Headache Pain and Most Bothersome Symptom When Initiated During a Migraine AttackA Randomized Clinical Trial

Question  Is the preventive migraine treatment intravenous eptinezumab effective when initiated during a migraine attack?

Findings  This randomized clinical trial included 480 patients eligible for preventive migraine therapy who had a moderate to severe migraine attack. Treatment with eptinezumab vs placebo during a migraine attack resulted in median time to headache pain freedom of 4 hours vs 9 hours and median time to absence of most bothersome symptom of 2 hours vs 3 hours, respectively; both comparisons were statistically significant.

Meaning  Among patients eligible for preventive migraine therapy, treatment with intravenous eptinezumab vs placebo during an active moderate to severe migraine attack shortened time to headache and migraine symptom freedom.

Importance  Intravenous eptinezumab, an anti–calcitonin gene-related peptide antibody, is approved for migraine prevention in adults. It has established onset of preventive efficacy on day 1 after infusion.

Objective  To evaluate the efficacy of and adverse events related to eptinezumab when initiated during a migraine attack.

Design, Setting, and Participants  Phase 3, multicenter, parallel-group, double-blind, randomized, placebo-controlled trial conducted from November 4, 2019, to July 8, 2020, at 47 sites in the United States and the country of Georgia. Participants (aged 18-75 years) with a greater than 1-year history of migraine and migraine on 4 to 15 days per month in the 3 months prior to screening were treated during a moderate to severe migraine attack.

Interventions  Eptinezumab, 100 mg (n = 238), or placebo (n = 242), administered intravenously within 1 to 6 hours of onset of a qualifying moderate to severe migraine.

Main Outcomes and Measures  Co-primary efficacy end points were time to headache pain freedom and time to absence of most bothersome symptom (nausea, photophobia, or phonophobia). Key secondary end points were headache pain freedom and absence of most bothersome symptom at 2 hours after start of infusion. Additional secondary end points were headache pain freedom and absence of most bothersome symptom at 4 hours and use of rescue medication within 24 hours.

Results  Of 480 randomized and treated patients (mean age, 44 years; 84% female), 476 completed the study. Patients treated with eptinezumab vs placebo, respectively, achieved statistically significantly faster headache pain freedom (median, 4 hours vs 9 hours; hazard ratio, 1.54 [P < .001]) and absence of most bothersome symptom (median, 2 hours vs 3 hours; hazard ratio, 1.75 [P < .001]). At 2 hours after infusion, in the respective eptinezumab and placebo groups, headache pain freedom was achieved by 23.5% and 12.0% (between-group difference, 11.6% [95% CI, 4.78%-18.31%]; odds ratio, 2.27 [95% CI, 1.39-3.72]; P < .001) and absence of most bothersome symptom by 55.5% and 35.8% (between-group difference, 19.6% [95% CI, 10.87%-28.39%]; odds ratio, 2.25 [95% CI, 1.55-3.25]; P < .001). Results remained statistically significant at 4 hours after infusion. Statistically significantly fewer eptinezumab-treated patients used rescue medication within 24 hours than did placebo patients (31.5% vs 59.9%, respectively; between-group difference, −28.4% [95% CI, −36.95% to −19.86%]; odds ratio, 0.31 [95% CI, 0.21-0.45]; P < .001). Treatment-emergent adverse events occurred in 10.9% of the eptinezumab group and 10.3% of the placebo group; the most common was hypersensitivity (eptinezumab, 2.1%; placebo, 0%). No treatment-emergent serious adverse events occurred.

Conclusions and Relevance  Among patients eligible for preventive migraine therapy experiencing a moderate to severe migraine attack, treatment with intravenous eptinezumab vs placebo shortened time to headache and symptom resolution. Feasibility of administering eptinezumab treatment during a migraine attack and comparison with alternative treatments remain to be established.

Trial Registration  ClinicalTrials.gov Identifier: NCT04152083