title: OnabotulinumtoxinA for the treatment of patients with overactive bladder and urinary incontinence: results of a phase 3, randomized, placebo controlled trial.
abstract: OBJECTIVE
  Overactive bladder affects 12% to 17% of the general population and almost a third experience urinary incontinence, which may severely impact health related quality of life. Oral anticholinergics are the mainstay of pharmacological treatment but they are limited by inadequate efficacy or side effects, leading to a high discontinuation rate. We report the results of the first large (557 patients), phase 3, placebo controlled trial of onabotulinumtoxinA in patients with overactive bladder and urinary incontinence inadequately managed with anticholinergics.
  
  
  METHODS
  Eligible patients with overactive bladder, 3 or more urgency urinary incontinence episodes in 3 days and 8 or more micturitions per day were randomized 1:1 to receive intradetrusor injection of onabotulinumtoxinA 100 U or placebo. Co-primary end points were the change from baseline in the number of urinary incontinence episodes per day and the proportion of patients with a positive response on the treatment benefit scale at posttreatment week 12. Secondary end points included other overactive bladder symptoms and health related quality of life. Adverse events were assessed.
  
  
  RESULTS
  OnabotulinumtoxinA significantly decreased the daily frequency of urinary incontinence episodes vs placebo (-2.65 vs -0.87, p <0.001) and 22.9% vs 6.5% of patients became completely continent. A larger proportion of onabotulinumtoxinA than placebo treated patients reported a positive response on the treatment benefit scale (60.8% vs 29.2%, p <0.001). All other overactive bladder symptoms improved vs placebo (p ≤ 0.05). OnabotulinumtoxinA improved patient health related quality of life across multiple measures (p <0.001). Uncomplicated urinary tract infection was the most common adverse event. A 5.4% rate of urinary retention was observed.
  
  
  CONCLUSIONS
  OnabotulinumtoxinA 100 U showed significant, clinically relevant improvement in all overactive bladder symptoms and health related quality of life in patients inadequately treated with anticholinergics and was well tolerated.
authors.affiliation: New York University Urology Associates, New York, New York, USA. Victor.Nitti@nyumc.org
authors.forename: Victor W
authors.initials: VW
authors.lastname: Nitti
authors.forename: Roger
authors.initials: R
authors.lastname: Dmochowski
authors.forename: Sender
authors.initials: S
authors.lastname: Herschorn
authors.forename: Peter
authors.initials: P
authors.lastname: Sand
authors.forename: Catherine
authors.initials: C
authors.lastname: Thompson
authors.forename: Christopher
authors.initials: C
authors.lastname: Nardo
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yan
authors.forename: Cornelia
authors.initials: C
authors.lastname: Haag-Molkenteller
mesh_terms: D000367:Age Factors; D000368:Aged; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage* / Q000009:adverse effects; D002170:Canada; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D015999:Multivariate Analysis; D011788:Quality of Life; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D012737:Sex Factors; D016896:Treatment Outcome; D014481:United States; D053201:Urinary Bladder, Overactive / Q000175:diagnosis / Q000188:drug therapy*; D014549:Urinary Incontinence / Q000175:diagnosis / Q000188:drug therapy*; D014563:Urodynamics
chemical_list: D019274:Botulinum Toxins, Type A