Abstract
Dear Editor,
We recently had the opportunity to review unpublished data from a sham-controlled, randomised double-blind study of a device: a single pulse transcranial magnetic stimulator (sTMS) (1). The study reported two-hour pain free rates in patients with migraine with aura who were instructed to treat early in the attack following the onset of aura. In the execution, patients treated when pain was absent or mild: sham (n = 55) and sTMS (n = 62), out of the total: sham (n = 82) and sTMS (n = 82). The two-hour pain free rates were 22% for placebo and 39% for sTMS (p = 0.0179). Blinding was well maintained, as outlined in the original publication (1).
Here we wish to document the two-hour pain free rate for patients entering this study with moderate or severe pain: 35% (n = 20) for sTMS and 7% (n = 27) for sham. Interestingly the two-hour pain free rate for placebo overall, 22%, reflected well what has been reported in other studies where mild pain was treated (2).
While certainly small numbers, it is remarkable that the pain free rate for placebo at two hours falls in the narrow range reported for serotonin 5-HT1B/1D receptor agonist, triptan (3), 5-HT1F receptor agonist, ditan (4) and calcitonin gene-related peptide (CGRP) receptor antagonist, gepant (5, 6), clinical trial programs. We offer the data, as is, to enrich discussion on placebo response rates in acute migraine studies. Our view is the data support the use of pain free rates at two hours as reliable measures in migraine clinical trials of acute treatments. This finding suggests that two-hour pain free rates for this device are in line with previous reports for drugs.
Footnotes
Declaration of conflicting interests
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Dr. Goadsby reports, unrelated to this note, grants and personal fees from Allergan, Amgen, and Eli-Lilly and Company; and personal fees from Akita Biomedical, Alder Biopharmaceuticals, Avanir Pharma, Cipla Ltd, Dr Reddy's Laboratories, eNeura, Electrocore LLC, Novartis, Pfizer Inc, Quest Diagnostics, Scion, Teva Pharmaceuticals, Trigemina Inc., Scion; and personal fees from MedicoLegal work, Journal Watch, Up-to-Date, Massachusetts Medical Society, Oxford University Press; and in addition, has a patent Magnetic stimulation for headache assigned to eNeura.
Dr Lipton He receives research support from the NIH: 2PO1 AG003949 (Program Director), 5U10 NS077308 (PI), 1RO1 AG042595 (Investigator), RO1 NS082432 (Investigator), K23 NS09610 (Mentor), K23AG049466 (Mentor). He also receives support from the Migraine Research Foundation and the National Headache Foundation. He serves on the editorial board of Neurology and as senior advisor to Headache. He has reviewed for the NIA and NINDS, holds stock options in eNeura Therapeutics and Biohaven Holdings; serves as consultant, advisory board member, or has received honoraria from: American Academy of Neurology, Alder, Allergan, American Headache Society, Amgen, Autonomic Technologies, Avanir, Biohaven, Biovision, Boston Scientific, Colucid, Dr. Reddy's, Electrocore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKlein, Merck, Pernix, Pfizer, Supernus, Teva, Trigemina, Vector, Vedanta. He receives royalties from Wolff's Headache, 8th Edition, Oxford Press University, 2009, Wiley and Informa.
Dr Dodick discloses the following: Consulting: Acorda, Allergan, Amgen, Alder, Dr Reddy's, Merck, Dr Reddy's, Promius, eNeura, Eli Lilly & Company, Insys therapeutics, Autonomic Technologies, Teva, Xenon, Tonix, Trigemina, Boston Scientific, GBS, Colucid, Zosano, Laydenburg Thalmann, Biocentric, Biohaven, Magellan, Pfizer (Japan), Charleston Laboratories. Royalties: Oxford University Press and Cambridge University Press (Book Royalty). Up-to-date editorial/honoraria. CME companies honoraria/publishing honoraria/royalites: Chameleon Communications, Medscape, WebMD, Academy for Continued Healthcare Learning, Haymarket Medical Education, Global Scientific Communications, HealthLogix, Academy for Continued Healthcare Learning, Meeting LogiX, Health LogiX, Wiley Blackwell, Oxford University Press, Cambridge University Press. Stock/options: GBS/Nocira, Epien, and Mobile Health. Consulting use agreement: NAS. Board position: King-Devick Inc.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.