Efficacy and Safety of OnabotulinumtoxinA for Idiopathic Overactive Bladder: A Double-Blind, Placebo Controlled, Randomized, Dose Ranging Trial
View All Author InformationAbstract
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.
References
- 1 : The standardisation of terminology in lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Urology2003; 61: 37. Google Scholar
- 2 : Reviewing the ICS 2002 terminology report: the ongoing debate. Neurourol Urodyn2009; 28: 287. Google Scholar
- 3 : The impact of urinary urgency and frequency on health-related quality of life in overactive bladder: results from a national community survey. Value Health2004; 7: 455. Google Scholar
- 4 : The impact of overactive bladder, incontinence and other lower urinary tract symptoms on quality of life, work productivity, sexuality and emotional well-being in men and women: results from the EPIC study. BJU Int2008; 101: 1388. Google Scholar
- 5 : Health-related quality of life among adults with symptoms of overactive bladder: results from a U.S. community-based survey. Urology2001; 57: 1044. Google Scholar
- 6 : Increased prevalence of aortic stenosis in patients with arteriovenous malformations of the gastrointestinal tract in Heyde syndrome. Arch Intern Med2003; 163: 1821. Google Scholar
- 7 : The effects of antimuscarinic treatments in overactive bladder: an update of a systematic review and meta-analysis. Eur Urol2008; 54: 543. Google Scholar
- 8 : Persistence and adherence of medications for chronic overactive bladder/urinary incontinence in the California Medicaid program. Value Health2005; 8: 495. Google Scholar
- 9 : Proposed mechanism for the efficacy of injected botulinum toxin in the treatment of human detrusor overactivity. Eur Urol2006; 49: 644. Google Scholar
- 10 : Botulinum-A toxin for treating detrusor hyperreflexia in spinal cord injured patients: a new alternative to anticholinergic drugs?: Preliminary results. J Urol2000; 164: 692. Link, Google Scholar
- 11 : Recommendations on the use of botulinum toxin in the treatment of lower urinary tract disorders and pelvic floor dysfunctions: a European consensus report. Eur Urol2009; 55: 100. Google Scholar
- 12 : Botulinum toxin A (Botox) intradetrusor injections in adults with neurogenic detrusor overactivity/neurogenic overactive bladder: a systematic literature review. Eur Urol2008; 53: 275. Google Scholar
- 13 : The effect of botulinum-A toxin on patients with severe urge urinary incontinence. J Urol2004; 172: 2316. Link, Google Scholar
- 14 : Botulinum A toxin injections into the detrusor: an effective treatment in idiopathic and neurogenic detrusor overactivity?. Neurourol Urodyn2005; 24: 231. Google Scholar
- 15 : Clinical effects of suburothelial injection of botulinum A toxin on patients with nonneurogenic detrusor overactivity refractory to anticholinergics. Urology2005; 66: 94. Google Scholar
- 16 : A comparison between the response of patients with idiopathic detrusor overactivity and neurogenic detrusor overactivity to the first intradetrusor injection of botulinum-A toxin. J Urol2005; 174: 984. Link, Google Scholar
- 17 : A prospective study to evaluate the safety, tolerability, efficacy and durability of response of intravesical injection of botulinum toxin type A into detrusor muscle in patients with refractory idiopathic detrusor overactivity. BJU Int2005; 96: 848. Google Scholar
- 18 : Experience with 100 cases treated with botulinum-A toxin injections in the detrusor muscle for idiopathic overactive bladder syndrome refractory to anticholinergics. J Urol2006; 176: 177. Link, Google Scholar
- 19 : Botulinum-A toxin detrusor and sphincter injection in treatment of overactive bladder syndrome: objective outcome and patient satisfaction. Eur Urol2005; 48: 984. Google Scholar
- 20 : Outcome of a randomized, double-blind, placebo controlled trial of botulinum A toxin for refractory overactive bladder. J Urol2009; 181: 2608. Link, Google Scholar
- 21 : Efficacy of botulinum toxin-A for treating idiopathic detrusor overactivity: results from a single center, randomized, double-blind, placebo controlled trial. J Urol2007; 177: 2231. Link, Google Scholar
- 22 : The placebo effect in the pharmacologic treatment of patients with lower urinary tract symptoms. Eur Urol2006; 50: 440. Google Scholar
- 23 : Refractory idiopathic urge urinary incontinence and botulinum A injection. J Urol2008; 180: 217. Link, Google Scholar
- 24 : Old words revisited–the importance of standardisation. Neurourol Urodyn2009; 28: 267. Google Scholar
