[ARTICLE] Dose-Dependent Effects of Abobotulinumtoxina (Dysport) on Spasticity and Active Movements in Adults With Upper Limb Spasticity: Secondary Analysis of a Phase 3 Study – Full Text

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 effect 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 (XV1) and angle of catch (XV3) were assessed with the Tardieu scale, and active range of motion (XA).

Results

At each muscle group level (finger, wrist, and elbow flexors) improvements in all outcome measures assessed (XV1, XV3, XA) were observed. In each muscle group, increases in abobotulinumtoxinA dose were associated with greater improvements in XV3 and XA, 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.

Introduction

Upper limb spasticity (ULS) is a common symptom after stroke and traumatic brain injury (TBI) and is associated with impaired self-care and additional burden of care [1-5]. Among several treatment strategies, guidelines recommend intramuscular botulinum toxin injections as a first-line treatment for adults with ULS [6-11].

Botulinum toxin type A (BoNT-A) injections may target upper extremity muscle groups from the shoulder, to decrease adductor and internal rotation tone, to the elbow, wrist, fingers, and thumb, to decrease flexor tone [12,13]. Specific muscle selection is based on the pattern of muscle overactivity, functional deficits, and patient goals [6]. These goals include increased passive and active range of motion, improved function (feeding and dressing), easier care (palmar and axillary hygiene), and reduction of pain [13].

Evidence-based information on optimal dosing for clinical use is relatively sparse. Dosing is not interchangeable between different BoNT-A products; therefore, improving our understanding of product-specific dosing will minimize confusion among injectors and improve the quality of patient care [13].

Among BoNT-A formulations, abobotulinumtoxinA (Dysport; Galderma Laboratories, LP, Fort Worth, TX) has been shown to decrease muscle tone (as measured by the Modified Ashworth Scale [MAS]) [13-17] and pain [18] and to facilitate goal attainment [19] in adults with ULS. A recent systematic review [13] of 12 randomized controlled trials (RCTs) in ULS concluded that abobotulinumtoxinA (total dose range, 500-1500 U) was generally well-tolerated, with “strong evidence” to support reduced muscle tone.

This paper presents the results of a secondary analysis from a recently published large international clinical trial, demonstrating improved active range of motion after abobotulinumtoxinA treatment in adults with hemiparesis and ULS >6 months after stroke or TBI [20]. This phase 3, randomized, double-blind, placebo-controlled study demonstrated that a total dose of either 500 U or 1000 U abobotulinumtoxinA injected in the upper extremity also resulted in decreased muscle tone and improvements in global physician-assessed clinical benefit compared with placebo.

Apart from a systematic measurement of active range of motion (XA) against finger, wrist, and elbow flexors, another unique aspect of the trial was the assessment of spasticity at the finger, wrist, and elbow flexor groups with the Tardieu scale (TS) [21,22]. The TS is a standardized evaluation used to assess the angle of arrest at slow speed (ie, passive range of motion, XV1) and the angle of catch at fast speed (XV3). The trial demonstrated improvements for finger, wrist, and elbow joints at week 4 in XV3 at both abobotulinumtoxinA doses and in XA at 1000 U; for the 500-U dose, improvements in XA were seen in the finger flexors. Both doses were associated with a favorable safety profile [20]. This analysis aims to provide a detailed description of improvements in spasticity and the active range of motion for individual muscle groups by dose and to provide information on muscle-specific dosing, which can be used in future recommendations for injectors.

Continue —> Dose-Dependent Effects of Abobotulinumtoxina (Dysport) on Spasticity and Active Movements in Adults With Upper Limb Spasticity: Secondary Analysis of a Phase 3 Study – ScienceDirect

 

Figure 1. Change from baseline of Tardieu scale parameters and of active range of motion week 4 postinjection in (A) extrinsic finger flexors, (B) wrist flexors, and (C) elbow flexors. Dose groups were as follows (lowest to highest dose): 500 U/non-PTMG, 500 U/PTMG, 1000 U/non-PTMG, and 1000 U/PTMG. Standard deviations and mean change from baseline values are detailed in Table 3. PTMG = primary targeted muscle group; XV1 = passive range of motion; XV3 = angle of catch at fast speed; XA = active range of motion.

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