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Atogepant for the preventive treatment of migraine

Research output: Contribution to journalArticlepeer-review

Jessica Ailani, Richard B. Lipton, Peter J. Goadsby, Hua Guo, Rosa Miceli, Lawrence Severt, Michelle Finnegan, Joel M. Trugman

Original languageEnglish
Pages (from-to)695-706
Number of pages12
JournalNew England Journal of Medicine
Volume385
Issue number8
DOIs
Published19 Aug 2021

Bibliographical note

Funding Information: Supported by Allergan (before acquisition by AbbVie). Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. A data sharing statement provided by the authors is available with the full text of this article at NEJM.org. We thank all the trial participants and investigators for their participation in this trial, and Amy Kuang, Ph.D. (full-time employee of AbbVie), for medical writing support. Publisher Copyright: Copyright © 2021 Massachusetts Medical Society. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

Abstract

BACKGROUND Atogepant is an oral, small-molecule, calcitonin gene-related peptide receptor antagonist that is being investigated for the preventive treatment of migraine.METHODS In a phase 3, double-blind trial, we randomly assigned adults with 4 to 14 migraine days per month in a 1:1:1:1 ratio to receive a once-daily dose of oral atogepant (10 mg, 30 mg, or 60 mg) or placebo for 12 weeks.The primary end point was the change from baseline in the mean number of migraine days per month across the 12 weeks.Secondary end points included headache days per month, a reduction from baseline of at least 50% in the 3-month average of migraine days per month, quality of life, and scores on the Activity Impairment in Migraine-Diary (AIM-D).RESULTS A total of 2270 participants were screened, 910 were enrolled, and 873 were included in the efficacy analysis; 214 were assigned to the 10-mg atogepant group, 223 to the 30-mg atogepant group, 222 to the 60-mg atogepant group, and 214 to the placebo group.The mean number of migraine days per month at baseline ranged from 7.5 to 7.9 in the four groups.The changes from baseline across 12 weeks were -3.7 days with 10-mg atogepant, -3.9 days with 30-mg atogepant, -4.2 days with 60-mg atogepant, and -2.5 days with placebo.The mean differences from placebo in the change from baseline were -1.2 days with 10-mg atogepant (95% confidence interval [CI], -1.8 to -0.6), -1.4 days with 30-mg atogepant (95% CI, -1.9 to -0.8), and -1.7 days with 60-mg atogepant (95% CI, -2.3 to -1.2) (P<0.001 for all comparisons with placebo).Results for the secondary end points favored atogepant over placebo with the exceptions of the AIM-D Performance of Daily Activities score and the AIM-D Physical Impairment score for the 10-mg dose.The most common adverse events were constipation (6.9 to 7.7% across atogepant doses) and nausea (4.4 to 6.1% across atogepant doses).Serious adverse events included one case each of asthma and optic neuritis in the 10-mg atogepant group.CONCLUSIONS Oral atogepant once daily was effective in reducing the number of migraine days and headache days over a period of 12 weeks.Adverse events included constipation and nausea.Longer and larger trials are needed to determine the effect and safety of atogepant for migraine prevention.(Funded by Allergan; ADVANCE ClinicalTrials.gov number, NCT03777059.)

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