Safety and efficacy of abobotulinumtoxinA for hemiparesis in adults with upper limb spasticity after stroke or traumatic brain injury: a double-blind randomised controlled trial.

Abstract

BACKGROUND:

Resistance from antagonistic muscle groups might be a crucial factor reducing function in chronic hemiparesis. The resistance due to spastic co-contraction might be reduced by botulinum toxin injections. We assessed the effects of abobotulinumtoxinA injection in the upper limb muscles on muscle tone, spasticity, active movement, and function.

METHODS:

In this randomised, placebo-controlled, double-blind study, we enrolled adults (aged 18-80 years) at least 6 months after stroke or brain trauma from 34 neurology or rehabilitation clinics in Europe and the USA. Eligible participants were randomly allocated in a 1:1:1 ratio with a computer-generated list to receive a single injection session of abobotulinumtoxinA 500 U or 1000 U or placebo into the most hypertonic muscle group among the elbow, wrist, or finger flexors (primary target muscle group [PTMG]), and into at least two additional muscle groups from the elbow, wrist, or finger flexors or shoulder extensors. Patients and investigators were masked to treatment allocation. The primary endpoint was the change in muscle tone (Modified Ashworth Scale [MAS]) in the PTMG from baseline to 4 weeks. Secondary endpoints were Physician Global Assessment (PGA) at week 4 and change from baseline to 4 weeks in the perceived function (Disability Assessment Scale [DAS]) in the principal target of treatment, selected by the patient together with physician from four functional domains (dressing, hygiene, limb position, and pain). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01313299.

FINDINGS:

243 patients were randomly allocated to placebo (n=81), abobotulinumtoxinA 500 U (n=81), or abobotulinumtoxinA 1000 U (n=81). Mean change in MAS score from baseline at week 4 in the PTMG was -0·3 (SD 0·6) in the placebo group (n=79), -1·2 (1·0) in the abobotulinumtoxinA 500 U group (n=80; difference -0·9, 95% CI -1·2 to -0·6; p<0·0001 vs placebo), and -1·4 (1·1) in the abobotulinumtoxinA 1000 U group (n=79; -1·1, -1·4 to -0·8; p<0·0001 vs placebo). Mean PGA score at week 4 was 0·6 (SD 1·0) in the placebo group (n=78), 1·4 (1·1) in the abobotulinumtoxinA 500 U group (n=80; p=0·0003 vs placebo), and 1·8 (1·1) in the abobotulinumtoxinA 1000 U group (n=78; p<0·0001 vs placebo). Mean change from baseline at week 4 in DAS score for the principal target of treatment was -0·5 (0·7) in the placebo group (n=79), -0·7 (0·8) in the abobotulinumtoxinA 500 U group (n=80; p=0·2560 vs placebo), and -0·7 (0·7) in the abobotulinumtoxinA 1000 U group (n=78; p=0·0772 vs placebo). Three serious adverse events occurred in each group and none were treatment related; two resulted in death (from pulmonary oedema in the placebo group and a pre-existing unspecified cardiovascular disorder in the abobotulinumtoxinA 500 U group). Adverse events that were thought to be treatment related occurred in two (2%), six (7%), and seven (9%) patients in the placebo, abobotulinumtoxinA 500 U, and abobotulinumtoxinA 1000 U groups, respectively. The most common treatment-related adverse event was mild muscle weakness. All adverse events were mild or moderate.

INTERPRETATION:

AbobotulinumtoxinA at doses of 500 U or 1000 U injected into upper limb muscles provided tone reduction and clinical benefit in hemiparesis. Future research into the treatment of spastic paresis with botulinum toxin should use active movement and function as primary outcome measures.

FUNDING:

Ipsen.

• Authors: Jean-Michel Gracies, Allison Brashear, Robert Jech, Peter McAllister, Marta Banach, Peter Valkovic, Heather Walker, Christina Marciniak, Thierry Deltombe, Alexander Skoromets, Svetlana Khatkova, Steven Edgley, Fatma Gul, France Catus, Beatrice Bois De Fer, Claire Vilain, Philippe Picaut, International AbobotulinumtoxinA Adult Upper Limb Spasticity Study Group
• Journal: The Lancet. Neurology (Lancet Neurol) Vol. 14 Issue 10 Pg. 992-1001 (Oct 2015) ISSN: 1474-4465 [Electronic] England
• PMID: 26318836 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Acetylcholine Release Inhibitors
• Botulinum Toxins, Type A
• abobotulinumtoxinA

Topics

• Acetylcholine Release Inhibitors (administration & dosage, adverse effects, pharmacology)
• Adult
• Botulinum Toxins, Type A (administration & dosage, adverse effects, pharmacology)
• Brain Injuries (complications)
• Double-Blind Method
• Female
• Humans
• Injections, Intramuscular
• Male
• Middle Aged
• Muscle Spasticity (drug therapy, etiology)
• Paresis (drug therapy, etiology)
• Stroke (complications)
• Treatment Outcome
• Upper Extremity (physiopathology)