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.