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Is the preventive migraine treatment intravenous eptinezumab effective when initiated during a migraine attack?
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.
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.
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.
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.
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.
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.
ClinicalTrials.gov Identifier: NCT04152083
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Corresponding Author: Roger Cady, MD, Lundbeck La Jolla Research Center, 10035 Road to the Cure, Ste 250, San Diego, CA 92121 (firstname.lastname@example.org).
Accepted for Publication: April 28, 2021.
Author Contributions: Dr Winner had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Mehta, Cady.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Winner, Ailani, Ettrup, Lindsten, Cady.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Krog Josiassen, Lindsten, Mehta.
Obtained funding: Ettrup, Cady.
Administrative, technical, or material support: Winner, McAllister, Ettrup, Mehta, Cady.
Supervision: Ailani, Ettrup, Krog Josiassen, Mehta, Cady.
Conflict of Interest Disclosures: Dr Winner reported receiving consulting fees from and serving on speaker bureaus for AbbVie, Amgen, Biohaven, Lilly, Lundbeck, Novartis, and Teva and receiving research support from AbbVie, Amgen, AZ, Biogen, Lilly, Lundbeck, Novartis, Supernus, and Teva. Dr McAllister reported receiving personal fees and research support from AbbVie, Amgen/Novartis, Biohaven, Lilly, Lundbeck, and Teva. Dr Ailani reported receiving clinical trial grants from AbbVie, Biohaven, Lilly, Satsuma, and Zosano; data monitoring board membership for Aeon; consulting fees from and/or advisory board membership for AbbVie, Amgen, Axsome, Biohaven, CtrlM, Electrocore, Lilly, Impel, Lundbeck, Promius, Revance, Satsuma, Teva, Theranica, Vorso, and Zosano; and speaker fees from AbbVie, Amgen, Biohaven, Electrocore, Lilly, Impel, Lundbeck, Promius, Satsuma, and Teva. Dr Ettrup, Dr Krog Josiassen, and Ms Lindsten are employees of Lundbeck. Dr Mehta was an employee of Lundbeck Seattle BioPharmaceuticals at the time of study. Dr Cady is an employee of and stockholder in Lundbeck. No other disclosures were reported.
Funding/Support: The study was sponsored and funded by H. Lundbeck A/S, including editorial support for the development of the manuscript.
Role of the Funder/Sponsor: In collaboration with the academic authors, the sponsor participated in the design and conduct of the study and in the collection, management, analysis, and interpretation of the data. The preparation, review, and approval of the manuscript was undertaken by all authors and by a professional medical writer and editor funded by the sponsor. Most statistical analyses were performed by a contracted research organization and were directed under contractual agreement with H. Lundbeck A/S; additional analyses were performed by Ms Lindsten, an employee of H. Lundbeck A/S. All authors and H. Lundbeck A/S prepared, reviewed, and approved the final version of the manuscript and made the decision to submit the manuscript for publication. The sponsor did not have the right to veto publication or to control the decision regarding to which journal the manuscript was submitted.
Data Sharing Statement: See Supplement 4.
Additional Contributions: We thank the patients, their families, and the sites that participated in this study. We also thank Nicole Coolbaugh, CMPP, and Sally-Anne Mitchell, PhD, of The Medicine Group LLC, for providing medical writing support, which was funded by H. Lundbeck A/S in accordance with Good Publication Practice guidelines.
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