Introduction: OnabotulinumtoxinA (onabotA) is approved for treatment of post-stroke upper limb spasticity (PSULS) at a maximum dose of 400U across elbow, wrist, and finger sites. Safety and efficacy of a higher dose for PSULS were evaluated in elbow and shoulder sites not previously assessed.
Methods: A multicenter, double-blind, randomized, placebo-controlled study evaluated a single treatment of onabotA 300U (150U: elbow flexors; 150U: shoulder adductors) or 500U (250U; 250U) vs placebo in adults with PSULS (Modified Ashworth Scale [MAS] score ≥3). Safety and efficacy were assessed at weeks 2, 4, 6, 8, and 12. The study was terminated early for administrative reasons.
Results: All 53 enrolled patients completed the study. Baseline characteristics were similar between groups, except the onabotA 500U group had more men. Most patients were Caucasian and had a cerebral ischemic stroke of moderate severity (mean=101.7 months before enrollment). Mean change from baseline in elbow MAS for onabotA 500U was significantly greater than placebo at all time points (300U at wks 2 and 4, Figure 1). Significant tone reductions were also observed in the shoulder adductors with 500U (wks 2 and 4). The proportion of treatment responders (≥1-grade reduction in elbow MAS) was numerically greater for onabotA 500U and 300U than placebo at all time points (300U significant [P<0.05] at wks 2, 4, and 8). CGI generally improved more with onabotA than placebo (not significant). AEs were typically mild/moderate, not related to treatment, and occurred in a similar proportion of both onabotA dose groups and a greater proportion of the placebo group (300U, 27.8%; 500U, 29.4%; placebo, 50%).
Conclusions: Preliminary results from this randomized trial investigating the safety and efficacy of higher-dose onabotA for elbow and shoulder spasticity indicate a dose-related benefit. At the higher dose of 500U onabotA, no new safety signals were observed; AEs did not appear to be dose-related. Funding: Allergan