OnabotulinumtoxinA (Botox®): A Review of its Use in the Treatment of Urinary Incontinence in Patients with Multiple Sclerosis or Subcervical Spinal Cord Injury

OnabotulinumtoxinA (BOTOX(®)) is a type A neurotoxin derived from Clostridium botulinum bacteria that is approved as treatment for urinary incontinence (UI) in patients with neurogenic detrusor overactivity resulting from multiple sclerosis (MS) or subcervical spinal cord injury (SCI) who are not adequately treated by antimuscarinics. This article reviews the pharmacology of intradetrusor onabotulinumtoxinA in this indication. The presumed mode of action of onabotulinumtoxinA in bladder disorders is by interfering with efferent innervation of the detrusor muscle and afferent pathways involved in the micturition reflex. In phase III trials in adult patients with MS or SCI with UI who were not adequately treated with antimuscarinics, intradetrusor onabotulinumtoxinA 200 U produced significantly greater mean changes (reductions) from baseline in UI episodes/week at week 6 than placebo (primary endpoint). Similar significant benefits of intradetrusor onabotulinumtoxinA 200 U over placebo were observed on other UI, urodynamic, health-related quality of life and treatment satisfaction endpoints. Intradetrusor onabotulinumtoxinA 200 U was generally well tolerated, with the most frequent adverse events being urinary tract infections and urinary retention. Few patients discontinued treatment because of adverse events. Based on interim analyses of an extension study of the phase III trials, repeat injections of onabotulinumtoxinA 200 U were similarly efficacious and well tolerated. Intradetrusor onabotulinumtoxinA represents a clinically important advance in the therapy of UI in patients with MS or SCI who have not responded to antimuscarinics or who are unable to tolerate antimuscarinics.