Pilot Single-Blind Trial of AbobotulinumtoxinA in Oromandibular Dystonia
Oromandibular dystonia (OMD) causes involuntary movements of masticatory and lingual muscles impairing eating, speaking, and swallowing. Treatment options are limited. The objective of this study was to determine the safety and efficacy of abobotulinumtoxinA (aboBoNTA) in OMD. A dose-finding study (phase 1) followed by a single session, prospective, single-blind trial (phase 2) was carried out. OMD subjects were evaluated at baseline, 6 and 12 weeks. Muscles injected were tailored to individual symptoms using EMG guidance, but the aboBoNTA dose for each muscle was pre-specified based on phase 1 results. Evaluations were Global Dystonia Rating Scale (GDS), Unified Dystonia Rating Scale (UDRS), Clinical Global Impression (CGI) improvement and severity, and quality of life (OMDQ-25). Adverse events were monitored. The lowest dosage in phase 1 resulted in adverse effects in two of three patients and thus was used in phase 2. In phase 2, adverse effects were observed in 50% of subjects including dysphagia, voice change, and soft palate weakness. Most were mild. Significant improvement was seen in quality of life (OMDQ-25), speech (BFMq21), and change in GDS, UDRS, CGI severity assessed by the unblinded investigator, but not in blinded video ratings. We conclude that aboBoNTA therapy in this study was associated with improved quality of life and was generally well tolerated in OMD, but occurrence of dysphagia dictated the importance of using low genioglossus dosing. Face to face assessment appears to be more sensitive than video assessment for change in OMD severity. Consideration of the disability in OMD places constraints on traditional placebo-control trial design. Development of novel trial designs is warranted.
KeywordsDystonia Oromandibular dystonia AbobotulinumtoxinA Quality of life Clinical trial
Scorr: drafting and revising manuscript, analysis or interpretation of data, acquisition of data
Silver: drafting and revising manuscript, study concept or design, obtaining funding
Hanfelt: drafting and revising manuscript, analysis or interpretation of data
Sperin: drafting and revising manuscript, acquisition of data
Freeman: drafting and revising manuscript, acquisition of data
Jinnah: drafting and revising manuscript, analysis or interpretation of data, acquisition of data
Factor: drafting and revising manuscript, study concept or design, analysis or interpretation of data, acquisition of data, study supervision or coordination, obtaining funding
Freeman: Honorarium Lundbeck
Jinnah: Dr. Jinnah is director of the Dystonia Coalition, which receives the majority of its support through National Institutes of Health (NIH) grants NS065701 and TR001456 from the Office of Rare Diseases Research at the National Center for Advancing Translational Sciences and the National Institute of Neurological Disorders and Stroke. The Dystonia Coalition has received additional material or administrative support from industry sponsors (Allergan Inc. and Merz Pharmaceuticals) as well as private foundations (Beat Dystonia, The Benign Essential Blepharospasm Foundation, Cure Dystonia Now, Dystonia Inc., Dystonia Ireland, The Dystonia Medical Research Foundation, The European Dystonia Federation, The Foundation for Dystonia Research, The National Spasmodic Dysphonia Association, The National Spasmodic Torticollis Association, Tyler’s Hope for a Dystonia Cure). Dr. Jinnah has also received research or training grants from the NIH, Pharmaceutical Companies (Ipsen Inc. and Merz Pharmaceuticals) and Private Foundations (the Benign Essential Blepharospasm Research Foundation, Cure Dystonia Now, Dystonia Medical Research Foundation, and the Lesch-Nyhan Syndrome Children’s Research Foundation). He also has served on an advisory board or as a consultant for Allergan, Inc., Ipsen Pharmaceuticals, Psyadon Therapeutics, Retrophin Inc., and Saol Therapeutics.
Factor: Honoraria: Neurocrine, Lundbeck, Auspex/Teva, Avanir, Cynapsus, Adamas, UCB.
Grants: Ipsen, Medtronics, Teva, US World Meds, Cynapsus Therapeutics, Solstice, Vaccinex, Voyager, CHDI Foundation, Michael J. Fox Foundation, NIH
Royalties: Demos, Blackwell Futura for textbooks, Uptodate
Ipsen Pharmaceuticals supported this study.
SAF is supported by the Sartain Lanier Family Foundation.
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