Efficacy and safety of onabotulinumtoxinA for idiopathic overactive bladder: a double-blind, placebo controlled, randomized, dose ranging trial

Purpose: Treatment options for patients with overactive bladder refractory to anticholinergics are limited. We assessed the dose response across a range of doses of onabotulinumtoxinA (BOTOX®) in patients with idiopathic overactive bladder and urinary urgency incontinence whose symptoms were not adequately managed with anticholinergics.

Materials and methods: In a phase 2, multicenter, randomized, double-blind study, 313 patients with idiopathic overactive bladder and urinary urgency incontinence experiencing 8 or more urinary urgency incontinence episodes a week and 8 or more micturitions daily at baseline received 50, 100, 150, 200 or 300 U intradetrusor onabotulinumtoxinA, or placebo. Symptoms were recorded using a 7-day bladder diary. The primary efficacy variable was weekly urinary urgency incontinence episodes and the primary end point was week 12.

Results: Demographics and baseline characteristics were balanced across the treatment groups. Durable efficacy was observed for all onabotulinumtoxinA dose groups of 100 U or greater for primary and secondary efficacy measures, including the proportion of incontinence-free patients. When the dose response curves were analyzed, doses greater than 150 U contributed minimal additional or clinically relevant improvement in symptoms. This finding was also reflected in health related quality of life assessments. Dose dependent changes in post-void residual urine volume were observed and the use of clean intermittent catheterization was also dose dependent. The only adverse events significantly greater with onabotulinumtoxinA than with placebo were urinary tract infection and urinary retention.

Conclusions: OnabotulinumtoxinA at doses of 100 U or greater demonstrated durable efficacy in the management of idiopathic overactive bladder and urinary urgency incontinence. A dose of 100 U may be the dose that appropriately balances the symptom benefits with the post-void residual urine volume related safety profile.