title: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Ipsen.
authors: EA 7377 BIOTN, Université Paris-Est, Hospital Albert Chenevier-Henri Mondor, Service de Rééducation Neurolocomotrice, Créteil, France. Electronic address: jean-michel.gracies@aphp.fr.
authors: Jean-Michel
authors: JM
authors: Gracies
authors: Wake Forest University School of Medicine, Department of Neurology, Winston-Salem, NC, USA.
authors: Allison
authors: A
authors: Brashear
authors: Department of Neurology, First Faculty of Medicine, Charles University and General Faculty Hospital, Prague, Czech Republic.
authors: Robert
authors: R
authors: Jech
authors: New England Institute for Neurology and Headache, Stamford, CT, USA.
authors: Peter
authors: P
authors: McAllister
authors: Department of Neurology, Jagiellonian University Medical College, Krakow, Poland.
authors: Marta
authors: M
authors: Banach
authors: Second Department of Neurology, Comenius University and University Hospital, Bratislava, Slovakia.
authors: Peter
authors: P
authors: Valkovic
authors: University of North Carolina, Chapel Hill, NC, USA.
authors: Heather
authors: H
authors: Walker
authors: Northwestern University and Rehabilitation Institute of Chicago, Chicago, IL, USA.
authors: Christina
authors: C
authors: Marciniak
authors: Service de Médecine Physique et de Réadaptation, Centre Hospitalier Universitaire Dinant Godinne/Université catholique de Louvain Namur, Yvoir, Belgium.
authors: Thierry
authors: T
authors: Deltombe
authors: State Budgetary Educational Institution of Higher Professional Education, St Petersburg State Medical University I P Pavlov, St Petersburg, Russia.
authors: Alexander
authors: A
authors: Skoromets
authors: Neurology Department, Federal State Hospital Treatments and Rehabilitation Center of Ministry of Health and Social Development of Russian Federation, Moscow, Russia.
authors: Svetlana
authors: S
authors: Khatkova
authors: University of Utah School of Medicine, Division of Physical Medicine and Rehabilitation, Salt Lake City, UT, USA.
authors: Steven
authors: S
authors: Edgley
authors: University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors: Fatma
authors: F
authors: Gul
authors: Assesoria Croissance, Santiago, Chile.
authors: France
authors: F
authors: Catus
authors: Ipsen Innovation, Les Ulis, France.
authors: Beatrice Bois
authors: BB
authors: De Fer
authors: Ipsen Innovation, Les Ulis, France.
authors: Claire
authors: C
authors: Vilain
authors: Ipsen Innovation, Les Ulis, France.
authors: Philippe
authors: P
authors: Picaut
mesh_terms: D065087:Acetylcholine Release Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000328:Adult; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001930:Brain Injuries / Q000150:complications*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D009128:Muscle Spasticity / Q000188:drug therapy* / Q000209:etiology; D010291:Paresis / Q000188:drug therapy* / Q000209:etiology; D020521:Stroke / Q000150:complications*; D016896:Treatment Outcome; D034941:Upper Extremity / Q000503:physiopathology*
chemical_list: D065087:Acetylcholine Release Inhibitors; D019274:Botulinum Toxins, Type A; C542869:abobotulinumtoxinA