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.
Design, setting, and participants: 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.
Intervention: OnabotulinumtoxinA at a 100U dose (n=277) or placebo (n=271), administered as 20 intradetrusor injections of 0.5 ml.
Outcome measurements and statistical analysis: 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).
Results and limitations: 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.
Trial registration: ClinicalTrials.gov: NCT00910520.
Keywords: Botulinum toxin; OnabotulinumtoxinA; Overactive bladder; Urinary incontinence.
Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.