Long-term safety of repeated high doses of incobotulinumtoxinA injections for the treatment of upper and lower limb spasticity after stroke

Current guidelines suggested a dosage up to 600 units (U) of botulinum toxin type A (BoNT-A) (onabotulinumtoxinA or incobotulinumtoxinA) in reducing spastic hypertonia with low prevalence of complications, although a growing body of evidence showed efficacy with the use of high doses (> 800 U). The available evidence mainly referred to a single set of injections evaluating the efficacy and safety of the neurotoxin 30 days after the treatment. In a prospective, non-randomized, open-label study, we studied the safety of repeated higher doses of incobotulinumtoxinA in post-stroke upper and lower limb spasticity. Two years after the first set of injections, we evaluated in 20 stroke survivors with upper and lower limb spasticity the long-term safety of repeated high doses of incobotulinumtoxinA (up to 840 U) for a total of eight sets of injections. Patients reported an improvement of their clinical picture concerning a reduction of spasticity measured with the Asworth Scale (AS) for elbow, wrist, fingers and ankle flexor muscles and disability measured with the Disability Assessment Scale (DAS) 30 days after the last set of injections (eighth set) compared to the baseline (p < 0.0001). No difference in AS and DAS scores has been found between t₁ (30 days after the first injection set) and t₂ (30 days after the eighth set of injections), with also similar safety. In a two-year follow-up, repeated high doses of incobotulinumtoxinA, administered for eight sets of injections, appeared to be safe in patients with upper and lower limb spasticity after stroke without general adverse effects.