title: An exploratory, placebo-controlled, dose-response study of the efficacy and safety of onabotulinumtoxinA in spinal cord injury patients with urinary incontinence due to neurogenic detrusor overactivity.
abstract: OBJECTIVE
  To explore the dose response to onabotulinumtoxinA 50, 100, and 200 U in patients with spinal cord injury (SCI) with urinary incontinence (UI) due to neurogenic detrusor overactivity (NDO).
  
  
  METHODS
  Patients (N = 73) with SCI (level T1 or lower) with NDO and UI (≥14 UI episodes/week) received 30 intradetrusor injections of onabotulinumtoxinA (50 U [n = 19], 100 U [n = 21], or 200 U [n = 17]) or placebo (n = 16) via cystoscopy, avoiding the trigone. Changes from baseline in UI episodes/week, volume voided/micturition, maximum cystometric capacity, and maximum detrusor pressure (MDP) during first involuntary detrusor contraction (IDC) were evaluated. Adverse events (AEs) were assessed.
  
  
  RESULTS
  A significant linear dose response for UI episodes/week was identified at weeks 18, 30, 36, 42, and 54 (P < 0.05) with a similar trend (P = 0.092) at week 6 (primary time point). A significant linear dose response was observed in volume/void at all post-treatment time points up to week 54 (P < 0.05) and in MDP during first IDC at week 6 (P = 0.034). The proportion of patients who achieved continence at week 6 was highest in the 200 U group. Duration of effect was longest with the 200 U dose, compared with other treatment groups. The AEs were comparable across groups; urinary tract infection was the most common AE across all treatment groups.
  
  
  CONCLUSIONS
  In this exploratory dose-response study of SCI patients with UI due to NDO, onabotulinumtoxinA 200 U was the most effective dose. The AE profile was comparable across all groups.
authors.affiliation: 2nd Department of Urology, Papageorgiou General Hospital, Aristotle University of Thessaloniki, 56403, Thessaloníki, Greece, zefxis@yahoo.co.uk.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Apostolidis
authors.forename: Catherine
authors.initials: C
authors.lastname: Thompson
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yan
authors.forename: Sherif
authors.initials: S
authors.lastname: Mourad
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019274:Botulinum Toxins, Type A / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D013119:Spinal Cord Injuries / Q000150:complications*; D016896:Treatment Outcome; D001750:Urinary Bladder, Neurogenic / Q000150:complications*; D053201:Urinary Bladder, Overactive / Q000150:complications*; D014549:Urinary Incontinence / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D014563:Urodynamics / Q000187:drug effects / Q000502:physiology
chemical_list: D019274:Botulinum Toxins, Type A