Dose-Dependent Effects of AbobotulinumtoxinA (Dysport) on Spasticity and Active Movements in Adults With Upper Limb Spasticity: Secondary Analysis of a Phase 3 Study

Abstract

Background: AbobotulinumtoxinA has beneficial effects on spasticity and active movements in hemiparetic adults with upper limb spasticity (ULS). However, evidence-based information on optimal dosing for clinical use is limited.

Objective: To describe joint-specific dose effects of abobotulinumtoxinA in adults with ULS.

Design: Secondary analysis of a phase 3 study (NCT01313299).

Setting: Multicenter, international, double-blind, placebo-controlled clinical trial.

Participants: A total of 243 adults with ULS >6 months after stroke or traumatic brain injury, aged 52.8 (13.5) years and 64.3% male, randomized 1:1:1 to receive a single-injection cycle of placebo or abobotulinumtoxinA 500 U or 1000 U (total dose).

Methods: The overall effects of injected doses were assessed in the primary analysis, which showed improvement of angles of catch in finger, wrist, and elbow flexors and of active range of motion against these muscle groups. This secondary analysis was performed at each of the possible doses received by finger, wrist, and elbow flexors to establish possible dose effects.

Main outcome measures: Angle of arrest (X_V1) and angle of catch (X_V3) were assessed with the Tardieu Scale, and active range of motion (X_A).

Results: At each muscle group level (finger, wrist, and elbow flexors) improvements in all outcome measures assessed (X_V1, X_V3, X_A) were observed. In each muscle group, increases in abobotulinumtoxinA dose were associated with greater improvements in X_V3 and X_A, suggesting a dose-dependent effect.

Conclusions: Previous clinical trials have established the clinical efficacy of abobotulinumtoxinA by total dose only. The wide range of abobotulinumtoxinA doses per muscle groups used in this study allowed observation of dose-dependent improvements in spasticity and active movement. This information provides a basis for future abobotulinumtoxinA dosing recommendations for health care professionals based on treatment objectives and quantitative assessment of spasticity and active range of motion at individual joints.

Level of evidence: I.