Efficacy and safety of onabotulinumtoxinA in patients with urinary incontinence due to neurogenic detrusor overactivity: A randomised, double-blind, placebo-controlled trial

Background: Neurogenic detrusor overactivity (NDO) frequently results in urinary incontinence (UI) which impairs quality of life (QOL) and puts the upper urinary tract at risk. Objective: To assess the effects of onabotulinumtoxinA (BOTOX®, Allergan, Inc.) on UI, urodynamic variables, and QOL in incontinent patients with NDO. Design, setting, and participants: This multicentre, randomised, double-blind, placebo-controlled study enrolled patients with multiple sclerosis (MS; n = 154) or spinal cord injury (SCI; n = 121) with UI due to NDO (≥14 UI episodes per week). Intervention: Patients received 30 intradetrusor injections of onabotulinumtoxinA 200 U (n = 92), 300 U (n = 91), or placebo (n = 92), avoiding the trigone. Measurements: Primary end point was change from baseline in UI episodes per week (week 6). Secondary end points included urodynamics (maximum cystometric capacity [MCC], maximum detrusor pressure during first involuntary detrusor contraction [P _detmaxIDC]), and Incontinence Quality of Life (I-QOL) total score. Adverse events (AEs) were assessed. Results and limitations: At baseline, mean UI episodes per week (33.5) were similar across groups. At week 6, onabotulinumtoxinA 200 U and 300 U significantly reduced UI episodes per week (-21.8 and -19.4, respectively) compared with placebo (-13.2; p < 0.01); onabotulinumtoxinA benefit was observed by the first posttreatment study visit at week 2. Improvements in MCC, P _detmaxIDC, and I-QOL at week 6 were significantly greater with both onabotulinumtoxinA doses than with placebo (p < 0.001). Benefits were observed in both the MS and SCI populations. The median time to patient request for retreatment was the same for both onabotulinumtoxinA doses (42.1 wk) and greater than placebo (13.1 wk; p < 0.001). Most frequent AEs were localised urologic events (urinary tract infections and urinary retention, which were dose related in patients not using clean intermittent catheterisation [CIC] at baseline). Significant increases in postvoid residual were observed in patients not using CIC prior to treatment, and 12%, 30%, and 42% of patients in the placebo, 200-U, and 300-U groups, respectively, initiated CIC posttreatment. Conclusions: OnabotulinumtoxinA significantly reduced UI and improved urodynamics and QOL in MS and SCI patients with NDO. Both doses were well tolerated with no clinically relevant differences in efficacy or duration of effect between the two doses (http://www.clinicaltrials.gov; NCT00461292).