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European UrologyVolume 62, issue 1, pages e1-e30, July 2012
Onabotulinumtoxin A for Idiopathic Overactive Bladder: Raising the Bar
Published online 18 April 2012, pages 158 - 159
Refers to article:
OnabotulinumtoxinA Improves Health-Related Quality of Life in Patients With Urinary Incontinence Due to Idiopathic Overactive Bladder: A 36-Week, Double-Blind, Placebo-Controlled, Randomized, Dose-Ranging Trial
Accepted 5 March 2012
July 2012 (Vol. 62, Issue 1, pages 148 - 157)
OnabotulinumtoxinA (BoNT-ONA) is approved in approximately 75 countries worldwide. The indication for its use ranges from treatment of frown lines between the brows, severe axillary hyperhidrosis, cervical dystonia, chronic migraine, upper limb spasticity, and blepharospasm to strabismus. And the success story continues. BoNT-ONA was recently approved for the treatment of neurogenic bladder overactivity due to multiple sclerosis (MS) and spinal cord injury. The approval for refractory idiopathic overactive bladder (OAB) is expected soon.
Since the first publication showing the beneficial effects of BoNT-ONA in the treatment of idiopathic bladder overactivity, only a few years have passed. Today BoNT-ONA is widely used off-label as a second-line treatment in this patient cohort, even though BoNT-ONA is still not approved. Why? BoNT-ONA has been shown to be effective for neurogenic detrusor activity and also for nonneurogenic bladder overactivity, and severe complications are rare , , , , , and . The main complications in patients with idiopathic OAB include an increase in postvoid residual urine, urinary tract infections, and temporary hematuria  and . Based on the observation that the effect of BoNT-ONA decreases over months, it is now widely recognised that repeated injections are also effective. The symptomatic improvement is maintained after repeated injections  and , and injections can be performed using local anesthesia . In addition, the only approved second-line therapy for refractory idiopathic OAB is sacral neuromodulation, a much more complex treatment; other options such as bladder augmentation and bladder catheterization remain unattractive. Furthermore, treatment with BoNT-ONA significantly improves health-related quality of life (HRQoL) in neurogenic and nonneurogenic patients. In 2007, Schurch and colleagues showed that treatment with BoNT-ONA improves HRQoL in patients with neurogenic urinary incontinence . When comparing patients with neurogenic and nonneurogenic bladder overactivity, improvement in HRQoL is greater in neurogenic patients after the first injection. However, after the second injection, improvements in HRQoL score are similar between the groups .
The article published by Dr. Clare Fowler and colleagues in this edition of European Urology reports the results of a double-blind randomised placebo-controlled, dose-ranging trial on disease-specific and general HRQoL in patients with urinary incontinence due to idiopathic OAB . The efficacy and safety results were reported previously  and . In the current analysis, the authors were able to show that in 313 patients, QoL improved as soon as 2 wk after the injection of ≥100 IU BoNT-ONA; this effect was retained for 36 wk.
Several aspects of this study are worth noting. The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) questionnaire is an adequate tool to assess general HRQoL and has been used for a number of chronic benign diseases such as MS and osteoarthritis but also in oncologic entities such as renal cell carcinoma (RCC)  and . When looking at the baseline scores of idiopathic OAB patients, the impact on QoL in this patient cohort becomes evident, showing similar scores as those for patients with MS and RCC. In summary, all HRQoL measurement tools used in the current study (Incontinence-Specific Quality-of-Life Instrument, King's Health Questionnaire, and SF-36 questionnaire) for BoNT-ONA at doses ≥100 U showed greater improvements in comparison with placebo, even though the differences were not significant for every dose and all the QoL parameters assessed. It must be noted that all HRQoL results were exploratory end points and not validated, which limits the value of the results. Another significant limitation, as the authors rightly point out, is the fact that the study was powered to evaluate differences in the primary end points (number of episodes of urinary urge incontinence after 12 wk of therapy) but not to assess differences between groups in the improvement of HRQoL results. The study also showed that BoNT-ONA <100 U is probably not as effective. So although the statistical differences of the current study should be interpreted with caution, it does confirm previous results showing HRQoL-related improvements of BoNT-ONA in patients with idiopathic OAB  and . Taking into consideration the efficacy and safety results from recent studies in this indication , , and , it adds another piece to the puzzle to reassure us that BoNT-ONA is beneficial in the treatment of idiopathic OAB, which is why approval is awaited soon.
Despite several studies showing the effectiveness and safety of BoNT-ONA for the treatment of refractory idiopathic OAB, until today many open questions remain: injection technique (ideal number of injections, concentration, site of injection), the use in children or in male patients with lower urinary tract symptoms, and concomitant voiding symptoms. And what happens in the long run, after several years of reinjections? Will the effect decrease over decades, and will antibody production be an issue? Thus although our patients in particular have high hopes for the treatment for idiopathic OAB, it remains to be seen if these expectations will be met. At present, considering BoNT-ONA as the “Viagra for incontinence” appears to be ironically true: a good option for many, but not for all.
Conflicts of interest
The authors have nothing to disclose.
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Department of Urology, University-Hospital Grosshadern, Ludwig-Maximilians-University, Munich, Germany
© 2012 Published by Elsevier B.V.
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