FollowTheSutures: Piloting a new way to administer onabotulinumtoxinA for chronic migraine

Abstract

Background: Anatomical and experimental data indicate that onabotulinimtoxin A could be more efficient and cost-effective for treating chronic migraine with injections targeting the cranial sutures, where collaterals from the meninges penetrate the skull.

Methods: A new injection paradigm (FollowTheSutures) was tested for safety, tolerability and feasibility in a Phase II, open-label, non-controlled, single-center pilot study. Ninety units of onabotulinimtoxin A (Botox®), were injected in 18 sites over the area of the cranial sutures. Adverse events and potential beneficial effects were recorded in a headache diary at least 4 weeks before, and for 12 weeks after the injections. A higher dilution than normal of onabotulinimtoxin A was used to get better diffusion.

Results: Nineteen (of 20 included) women with chronic migraine received the injections and were evaluable. There was only one treatment-related adverse event (reduced power of chewing for some weeks). Otherwise, the procedure was overall well tolerated. Patients improved on most efficacy parameters after the injections. There was little or no effect on glabellar or forehead lines.

Conclusions: The protocol was safe and well tolerated. Lower risk of unblinding due to the absence of cosmetic effects should make the injection procedure well suited for a large, randomized, placebo-controlled study. If efficacy is confirmed, it will be markedly less costly than the standard procedure.Trial registration: EUDRACT (2017-002516-13), ClinicalTrials.gov (NCT03543254).

Keywords: Cranial sutures; injections; pilot study.

Conflict of interest statement

Declaration of conflicting interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: LJS has received lecture fees and research contributions from Allergan, Novartis, Teva, Lilly, and Lundbeck.

KH reports no competing interests.

ET has received consultant fees from Allergan, Amgen, Novartis, Eli Lilly, Teva, Roche, Lundbeck, is a board member and shareholder in Palion Medical AS, and shareholder in Nordic Brain Tech AS.

GBG has received consultant fees from Novartis and has been on an advisory board for Allergan and Lundbeck.

RB is a consultant for and has received research funds from Allergan.

DWD reports the following conflicts within the past 12 months: Consulting: Amgen, Atria, Cerecin, Cooltech, Ctrl M, Allergan, Biohaven, GSK, Lundbeck, Eli Lilly, Novartis, Impel, Satsuma, Theranica, WL Gore, Nocira, Praxis, AYYA Biosciences, Revance. Honoraria: Clinical Care Solutions, CME Outfitters, Curry Rockefeller Group, DeepBench, Global Access Meetings, KLJ Associates, Academy for Continued Healthcare Learning, Majallin LLC, Medlogix Communications, MJH Lifesciences, Miller Medical Communications, WebMD Health/Medscape, Wolters Kluwer, Oxford University Press, Cambridge University Press. Research support: Department of Defense, National Institutes of Health, Henry Jackson Foundation, Sperling Foundation, American Migraine Foundation, Patient Centered Outcomes Research Institute (PCORI). Stock Options/Shareholder/Patents/Board of Directors: Ctrl M (options), Aural analytics (options), ExSano (options), Palion (options), Healint (options), Theranica (options), Second Opinion/Mobile Health (options), Epien (options/Board), Nocira (options), Matterhorn (shares/Board), Ontologics (shares/Board), King-Devick Technologies (options/Board), Precon Health (options/Board), AYYA Biosciences. Patent 17189376.1-1466:vTitle: Botulinum Toxin Dosage Regimen for Chronic Migraine Prophylaxis.

Figures

Figure 1.

Locations of OnabotulinumtoxinA injections. For some points (1,2,5,7,9) the distance from easily identifiable landmarks is given. Points 6,8,10 were midway between two other points (5 and 2, 5 and 7, and 1 and 9), and 3 and 4 were distributed evenly between 1 and 2. Five units of BoNTA were given at each point.