title: OnabotulinumtoxinA 100 U significantly improves all idiopathic overactive bladder symptoms and quality of life in patients with overactive bladder and urinary incontinence: a randomised, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Overactive bladder (OAB) syndrome with urinary incontinence (UI) is prevalent in the population and impairs health-related quality of life (HRQOL).
  
  
  OBJECTIVE
  To assess the impact on efficacy, safety, and HRQOL of onabotulinumtoxinA (BOTOX(®), Allergan, Inc.) treatment in patients with OAB with UI.
  
  
  METHODS
  This pivotal, multicentre, double-blind, randomised, placebo-controlled, phase 3 study enrolled patients with idiopathic OAB with ≥ 3 urgency UI episodes over 3 d and ≥ 8 micturitions per day who were inadequately managed by anticholinergics.
  
  
  METHODS
  OnabotulinumtoxinA at a 100U dose (n=277) or placebo (n=271), administered as 20 intradetrusor injections of 0.5 ml.
  
  
  METHODS
  Co-primary end points were change from baseline in the number of UI episodes per day and proportion of patients reporting positive treatment response on the treatment benefit scale (TBS) at week 12. Additional end points included other OAB symptoms (episodes of urinary urgency incontinence, micturition, urgency, and nocturia) and HRQOL (Incontinence Quality of Life [I-QOL], King's Health Questionnaire [KHQ]). Safety assessments included adverse events (AEs), postvoid residual (PVR) urine volume, and initiation of clean intermittent catheterisation (CIC).
  
  
  CONCLUSIONS
  OnabotulinumtoxinA significantly decreased UI episodes per day at week 12 (-2.95 for onabotulinumtoxinA versus -1.03 for placebo; p<0.001). Reductions from baseline in all other OAB symptoms were also significantly greater following onabotulinumtoxinA compared with placebo (p ≤ 0.01). Patients perceived a significant improvement in their condition, as measured by patients with a positive treatment response on the TBS (62.8% for onabotulinumtoxinA versus 26.8% for placebo; p<0.001). Clinically meaningful improvements from baseline in all I-QOL and KHQ multi-item domains (p<0.001 versus placebo) indicated positive impact on HRQOL. AEs were mainly localised to the urinary tract. Mean PVR was higher in the onabotulinumtoxinA group (46.9 ml versus 10.1 ml at week 2; p<0.001); 6.9% of onabotulinumtoxinA patients versus 0.7% of placebo patients initiated CIC.
  
  
  CONCLUSIONS
  OnabotulinumtoxinA 100 U was well tolerated and demonstrated significant and clinically relevant improvements in all OAB symptoms, patient-reported benefit, and HRQOL in patients inadequately managed by anticholinergics.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT00910520.
authors.affiliation: Royal Hallamshire Hospital, Sheffield, UK. c.r.chapple@shef.ac.uk
authors.forename: Christopher
authors.initials: C
authors.lastname: Chapple
authors.forename: Karl-Dietrich
authors.initials: KD
authors.lastname: Sievert
authors.forename: Scott
authors.initials: S
authors.lastname: MacDiarmid
authors.forename: Vik
authors.initials: V
authors.lastname: Khullar
authors.forename: Piotr
authors.initials: P
authors.lastname: Radziszewski
authors.forename: Christopher
authors.initials: C
authors.lastname: Nardo
authors.forename: Catherine
authors.initials: C
authors.lastname: Thompson
authors.forename: Jihao
authors.initials: J
authors.lastname: Zhou
authors.forename: Cornelia
authors.initials: C
authors.lastname: Haag-Molkenteller
mesh_terms: D000328:Adult; D000368:Aged; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018680:Cholinergic Antagonists / Q000627:therapeutic use; D004311:Double-Blind Method; D005060:Europe; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D009465:Neuromuscular Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011788:Quality of Life; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D053202:Urinary Incontinence, Urge / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D014554:Urination / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects
chemical_list: D018680:Cholinergic Antagonists; D009465:Neuromuscular Agents; D019274:Botulinum Toxins, Type A
keywords: Botulinum toxin; OnabotulinumtoxinA; Overactive bladder; Urinary incontinence