title: Efficacy, tolerability, and immunogenicity of onabotulinumtoxina in a randomized, double-blind, placebo-controlled trial for cervical dystonia.
abstract: OBJECTIVE
  To evaluate the efficacy, tolerability, and neutralizing antibodies in the treatment of cervical dystonia with onabotulinumtoxinA (BOTOX).
  
  
  METHODS
  Subjects received onabotulinumtoxinA (containing original bulk toxin) treatment in a 10-week open-label period (period 1). Eligible subjects who completed this period were randomized to onabotulinumtoxinA or placebo in a 10-week double-blind period (period 2). The primary outcome measures were the Cervical Dystonia Severity Scale and the physician Global Assessment Scale at week 6 in period 2. Serum samples for immunogenicity tests were taken at baseline and study exit. The potential impact of preexisting neutralizing antibodies (nAbs) was examined across subgroups for period 1 and by analysis of covariance for period 2.
  
  
  RESULTS
  Of 214 subjects enrolled in period 1, 170 enrolled in period 2 and received placebo (n = 82) or onabotulinumtoxinA (n = 88). In period 1, subjects with preexisting nAbs responded similarly to those without preexisting nAbs. In period 2, onabotulinumtoxinA produced significantly greater improvements than placebo on the Cervical Dystonia Severity Scale (-1.81 vs -0.31 points; P = 0.012) and physician Global Assessment Scale (61.7% vs. 41.6% improved; P = 0.022) at the primary time point week 6, using baseline severity and neutralizing antibody (nAb) status at study entry as covariates. Two subjects seroconverted from nAb negative at baseline to nAb positive at study exit but remained responsive to onabotulinumtoxinA during both the open and blinded treatment periods. Rhinitis and treatment-related dysphagia were reported significantly more frequently with onabotulinumtoxinA than placebo.
  
  
  CONCLUSIONS
  OnabotulinumtoxinA was well tolerated and more effective than placebo for the treatment of cervical dystonia. Subject nAb status at baseline was not a clear predictor of response to onabotulinumtoxinA.
authors.affiliation: Department of Neurology, Vanderbilt University School of Medicine, Nashville, TN, USA. david.charles@vanderbilt.edu
authors.forename: David
authors.initials: D
authors.lastname: Charles
authors.forename: Allison
authors.initials: A
authors.lastname: Brashear
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hauser
authors.forename: Hung-Ir
authors.initials: HI
authors.lastname: Li
authors.forename: Lee-Ming
authors.initials: LM
authors.lastname: Boo
authors.forename: Mitchell F
authors.initials: MF
authors.lastname: Brin
mesh_terms: D000328:Adult; D000368:Aged; D019274:Botulinum Toxins, Type A / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D014103:Torticollis / Q000188:drug therapy* / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D019274:Botulinum Toxins, Type A