Why Do Patients Discontinue Botulinum Toxin for Dystonia?
Limb Dystonia
In limb dystonia, mostly occupational dystonias have been studied, including writer’s cramp and musician’s dystonia. The most frequent adverse event with botulinum toxin is weakness, which may lead to discontinuation. In a 2007 study of abobotulinumtoxinA for writer’s cramp that used continuation of treatment as the primary outcome, 70% of patients who received active treatment continued treatment, compared with 32% of patients in the placebo group. Hand weakness occurred in about 90% of patients in the active treatment group, however, compared with 25% of patients in the placebo group, and 25% of patients in the active treatment group discontinued because of hand weakness.
Neurologists adjust a patient’s injections based on the patient’s response to the previous treatment, so treatment may become more beneficial as neurologists optimize the injection pattern and dosing.
Why Might Treatment Fail?
Injection of botulinum toxin into the wrong muscle may be a common reason for lack of efficacy. Stress-induced exacerbation or inadequate dose may be other reasons for treatment failure. Uncommon reasons for lack of efficacy include change in dystonia and immunoresistance. In addition, patients may discontinue treatment because of the expense or inconvenience, Dr. Comella said.
Neurologists should help set realistic expectations for treatment. “We must manage patient expectations. It is not a cure. This may not restore you to perfect movement,” Dr. Comella said. “Too often we tell them how well they are going to do without giving them a more realistic view.”
Future Directions
Neurologists need better long-term outcome data to understand the effects of botulinum toxin in dystonia, and telemedicine may be an ideal way to assess the treatment’s long-term efficacy, Dr. Comella said. Remote evaluations could supplement in-person evaluations and avoid reliance on patients’ retrospective reports.
An investigational formulation of botulinum toxin, daxibotulinumtoxinA, is being developed by Revance Pharmaceuticals. It contains a peptide excipient that is designed to produce a longer treatment effect. A phase II open-label study is evaluating the formulation in patients with cervical dystonia, said Dr. Comella, who is one of the study investigators. One cohort of 12 patients received between 100 units and 200 units of the neurotoxin. The patients’ mean Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) score change from baseline was 33% at 24 weeks. Investigators observed a clinically meaningful benefit by Week 2. The preliminary results are promising, but “we have much more work to do before this [formulation] could be available to us,” Dr. Comella said.
—Jake Remaly
Suggested Reading
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Evidente VG, Truong D, Jankovic J, et al. IncobotulinumtoxinA (Xeomin) injected for blepharospasm or cervical dystonia according to patient needs is well tolerated. J Neurol Sci. 2014;346(1-2):116-120.
Jankovic J, Adler CH, Charles D, et al. Primary results from the cervical dystonia patient registry for observation of onabotulinumtoxina efficacy (CD PROBE). J Neurol Sci. 2015;349(1-2):84-93.
Kruisdijk JJ, Koelman JH, Ongerboer de Visser BW, et al. Botulinum toxin for writer’s cramp: a randomised, placebo-controlled trial and 1-year follow-up. J Neurol Neurosurg Psychiatry. 2007;78(3):264-270.
Martinez-Ramirez D, Giugni JC, Hastings E, et al. Comparable botulinum toxin outcomes between primary and secondary blepharospasm: A retrospective analysis. Tremor Other Hyperkinet Mov (NY). 2014;4:286.
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Simpson DM, Blitzer A, Brashear A, et al. Assessment: Botulinum neurotoxin for the treatment of movement disorders (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2008;70(19):1699-1706.
Simpson DM, Hallett M, Ashman EJ, et al. Practice guideline update summary: Botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2016;86(19):1818-1826.
