@article{efb4b3fcb2f24f8b9e545c386d096f6d,
title = "Non-invasive vagus nerve stimulation for prevention of migraine: The multicenter, randomized, double-blind, sham-controlled PREMIUM II trial",
abstract = "Aim: Evaluate the efficacy and safety of non-invasive vagus nerve stimulation for migraine prevention. Methods: After completing a 4-week diary run-in period, adults who had migraine with or without aura were randomly assigned to receive active non-invasive vagus nerve stimulation or sham therapy during a 12-week double-blind period. Results: Of 336 enrolled participants, 113 (active, n = 56; sham, n = 57) completed ≥70 days of the double-blind period and were ≥66% adherent with treatment, comprising the prespecified modified intention-to-treat population. The COVID-19 pandemic led to early trial termination, and the population was ∼60% smaller than the statistical target for full power. Mean reduction in monthly migraine days (primary endpoint) was 3.12 for the active group and 2.29 days for the sham group (difference, −0.83; p = 0.2329). Responder rate (i.e. the percentage of participants with a ≥50% reduction in migraine days) was greater in the active group (44.87%) than the sham group (26.81%; p = 0.0481). Prespecified subgroup analysis suggested that participants with aura responded preferentially. No serious device-related adverse events were reported. Conclusions: These results suggest clinical utility of non-invasive vagus nerve stimulation for migraine prevention, particularly for patients who have migraine with aura, and reinforce the well-established safety and tolerability profile of this therapy. Trial Registration: ClinicalTrials.gov (NCT03716505).",
keywords = "Neuromodulation, clinical trial, migraine prophylaxis, nonpharmacologic treatment, preventive therapy",
author = "Umer Najib and Timothy Smith and Nada Hindiyeh and Joel Saper and Barbara Nye and Sait Ashina and McClure, {Candace K.} and Marmura, {Michael J.} and Serena Chase and Eric Liebler and Lipton, {Richard B.}",
note = "Funding Information: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Umer Najib is a consultant for and received honoraria from Abbvie. Timothy Smith is a consultant and advisor for Alder/Lundbeck, Amgen, Allergan/Abbvie, Biohaven, Impel Neurpharma, Lilly, Neurolief, and Nocira and has served on Speaker Bureaus for Amgen, Allergan/Abbvie, Biohaven, and Lilly. Nada Hindiyeh is a consultant and advisory board member for Lundback, Lilly, and Impel. Joel Saper received research grants from Allergan Pharmaceuticals, Amgen, Inc., Axsome Therapeutics, Inc, Biohaven Pharmaceuticals, Colucid Pharmaceuticals, Electrocore, Eli Lilly, Equinox Opthalmic, Inc., H. Lundbeck A/S, Impax Laboratories Inc., the FDA (NIH Grant), Novartis Pharmaceuticals Corp., Satsuma Pharmaceuticals Inc., Teva Branded Pharmaceutical & Upsher-Smith Laboratories, LLC., and Currax Pharmaceuticals. Barbara Nye serves on advisory boards for BioDelivery Sciences and Impel. Sait Ashina received honoraria for consulting from Allergan/AbbVie, Biohaven, Eli Lilly, Impel NeuroPharma, Theranica and Percept, is associate editor for Neurology Reviews and BMC Neurology, review editor for Frontiers in Neurology, serves on Advisory Board for Journal of Headache and Pain, and is a member of the Education Committee of the International Headache Society. Candace McClure declares no conflict of interest. Michael Marmura is on the Speaker Bureau of and a consultant for of Lilly. Consultant for Alder/Lumbeck and Theranica. Receives authorship and royalties of Medlink, Cambridge University Press, and Demos Medical. Serena Chase is a paid consultant of electroCore, Inc. Eric Liebler is an employee of electroCore, Inc. and receives stock ownership. Richard B. Lipton receives research support from the NIH, the FDA, the S&L Marx Foundation, the Migraine Research Foundation, and the National Headache Foundation. He holds stock options in Biohaven Holdings and CtrlM Health. He serves as consultant or advisory board member and has received honoraria from or research support from Abbvie (Allergan), American Academy of Neurology, American Headache Society, Amgen, Biohaven, Biovision, Boston, Dr. Reddy{\textquoteright}s (Promius), Electrocore, Eli Lilly, eNeura, Equinox, GlaxoSmithKline, Grifols, Lundbeck (Alder), Merck, Pernix, Pfizer, Teva, Vector, and Vedanta. Funding Information: Writing and editorial support was provided by Elizabeth Barton of MedLogix Communications, LLC, in cooperation with the authors, and was funded by electroCore, Inc. The authors have authorized the submission of this manuscript via a submitting agent and approved all statements of conflict of interest and provided final approval prior to submission. The authors would like to thank Danny Benmoshe, David True, Lazlo Mechtler, Deborah Friedman, Alexander Feoktistov, Abigail Chua, Christina Treppendahl, Ira Turner, Peter McAllister, Steve Meyers, Brian Plato, Maria Carmen Wilson, Cori Millen, Jack Schim, Deborah Reed, Carol Redillas, Nina Riggns, Artem Kaplan, and Thomas G. Ledbetter for contributing to data acquisition. Publisher Copyright: {\textcopyright} International Headache Society 2022.",
year = "2022",
month = jun,
doi = "10.1177/03331024211068813",
language = "English (US)",
volume = "42",
pages = "560--569",
journal = "Cephalalgia",
issn = "0333-1024",
publisher = "SAGE Publications Ltd",
number = "7",
}