Abstract
Botulinum toxin (BT) used for dystonia and spasticity is dosed according to the number of target muscles and the severity of their muscle hyperactivities. With this no other drug is used in a broader dose range than BT. The upper end of this range, however, still needs to be explored. We wanted to do this by a prospective non-interventional study comparing a randomly selected group of dystonia and spasticity patients receiving incobotulinumtoxinA (Xeomin®) high-dose therapy (HD group, n = 100, single dose ≥400 MU) to a control group receiving incobotulinumtoxinA regular-dose therapy (RD group, n = 30, single dose ≤200 MU). At the measurement point all patients were evaluated for systemic BT toxicity, i.e. systemic motor impairment or systemic autonomic dysfunction. HD group patients (56.1 ± 13.8 years, 46 dystonia, 54 spasticity) were treated with Xeomin® 570.1 ± 158.9 (min 400, max 1,200) MU during 10.2 ± 7.0 (min 4, max 37) injection series. In dystonia patients the number of target muscles was 46 and the dose per target muscle 56.4 ± 19.1 MU, in spasticity patients 35 and 114.9 ± 67.1 MU. HD and RD group patients reported 58 occurrences of items on the systemic toxicity questionnaire. Generalised weakness, being bedridden, feeling of residual urine and constipation were caused by the underlying tetra- or paraparesis, blurred vision by presbyopia. Dysphagia and dryness of eye were local BT adverse effects. Neurologic examination, serum chemistry and full blood count did not indicate any systemic adverse effects. Elevated serum levels for creatine kinase/MB, creatine kinase and lactate dehydrogenase were most likely iatrogenic artefacts. None of the patients developed antibody-induced therapy failure. Xeomin® can be used safely in doses ≥400 MU and up to 1,200 MU without detectable systemic toxicity. This allows expanding the use of BT therapy to patients with more widespread and more severe muscle hyperactivity conditions. Further studies—carefully designed and rigorously monitored—are necessary to explore the threshold dose for clinically detectable systemic toxicity.
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References
Aurora SK, Winner P, Freeman MC, Spierings EL, Heiring JO, DeGryse RE, VanDenburgh AM, Nolan ME, Turkel CC (2011) OnabotulinumtoxinA for treatment of chronic migraine: pooled analyses of the 56-week PREEMPT clinical program. Headache 51:1358–1573
Bocouture: Summary of Product Characteristics (2013). www.medicines.org.uk/emc/medicine/23251
Botox®: Summary of Product Characteristics (2013). www.medicines.org.uk/emc/medicine/112
Dressler D (2004a) Clinical presentation and management of antibody-induced failure of botulinum toxin therapy. Mov Disord Suppl 8:S92–S100
Dressler D (2004b) New formulation of BOTOX®: complete antibody-induced therapy failure in hemifacial spasm. J Neurol 251:360
Dressler D (2005) Botulism caused by consumption of smoked salmon. Nervenarzt 76:763–766
Dressler D (2012) Clinical applications of botulinum toxin. Curr Opin Microbiol 15:325–336
Dressler D, Benecke R (2003) Autonomic side effects of botulinum toxin type B treatment of cervical dystonia and hyperhidrosis. Eur Neurol 49:34–38
Dressler D, Dirnberger G (2000) Botulinum toxin therapy: risk factors for therapy failure. Mov Disord 15(suppl 2):51
Dressler D, Wohlfahrt K, Meyer-Rogge E, Wiest L, Bigalke H (2011) Antibody-induced botulinum toxin therapy failure in dermal indications. Dermatol Surg 36(Suppl 4):2182–2187
Girlanda P, Vita G, Nicolosi C, Milone S, Messina (1992) Botulinum toxin therapy: distant effects on neuromuscular transmission and autonomic nervous system. J Neurol Neurosurg Psychiatry 55:844–845
Göschel H, Wohlfarth K, Frevert J, Dengler R, Bigalke H (1997) Botulinum A toxin therapy: neutralizing and nonneutralizing antibodies–therapeutic consequences. Exp Neurol 147:96–102
Lange DJ, Brin MF, Warner CL, Fahn S, Lovelace R (1987) Distant effects of local injection of botulinum toxin. Muscle Nerve 10:552–555
Olney RK, Aminoff MJ, Gelb DJ, Lowenstein DH (1988) Neuromuscular effects distant from the site of botulinum neurotoxin injection. Neurology 38:1780–1783
Rosow DE, Parikh P, Vivero RJ, Casiano RR, Lundy DS (2013) Considerations for initial dosing of botulinum toxin in treatment of adductor spasmodic dysphonia. Otolaryngol Head Neck Surg 148:1003–1006
Scott AB (1980) Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery. J Pediatr Ophthalmol Strabismus 17:21–25
Truong D, Dressler D, Hallett M (2009) Manual of botulinum toxin therapy. Cambridge University Press, Cambridge
Vistabel: Summary of Product Characteristics (2013). www.medicines.org.uk/emc/medicine/17580
Xeomin®: Summary of Product Characteristics (2013). www.medicines.org.uk/emc/medicine/20666
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The help of F. Francis, MD; K. Escher, MD; P. Tacik, MD and Mrs H Gorzolla with patient and data management is greatly appreciated.
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Dressler, D., Adib Saberi, F., Kollewe, K. et al. Safety aspects of incobotulinumtoxinA high-dose therapy. J Neural Transm 122, 327–333 (2015). https://doi.org/10.1007/s00702-014-1252-9
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DOI: https://doi.org/10.1007/s00702-014-1252-9