Botulinum toxin for the treatment of overactive bladder: a single institute experience
Overactive bladder syndrome (OAB) is a complex disease. It is associated with social embarrassment, depression and loss of work productivity. It is usually treated with antimuscarinics drugs, even if antimuscarinics may be associated with side effects that result in poor persistence and contribute to anticholinergic burden, particularly in those taking other medications with anticholinergic properties. Recentely Mirabegron has been investigated as a potential alternative to antimuscarinics (1),(2). Intravesical Botulinum injection is an effective treatment for overactive bladder in patients that are refractory to antimuscarinics. Botulinum toxin significantly improves OAB symptoms and urodynamic parameters in patients with OAB (3). The aim of this study is to evaluate our experience in the use of Botulinum toxin for OAB.
Materials and Methods
We conducted a retrospective analysis of patients treated with botulinum toxin for overactive bladder between June 2012 and January 2015 at our institution. A total of 70 patients were enrolled (45 women and 25 men). All patients enrolled in this study had failed a 8 months treatment with 2 different oral pharmacological therapies. All patients also suffered of urge incontinence. and used more than one pad/day. Patients with neurogenic detrusor overactivity and/or severe detrusor underactivity were excluded from the study. Prior to the BoNT-A injections all patients underwent an uroflussimetry and an urodynamic exam. We used onabotulinumtoxinA (BoNT-A). The injections were done cystoscopically by a single operator. Average dose of BoNT-A was 100 units. The BoNT-A (total volume 10 mL) was administered as intradetrusor injections across 20 sites on the lateral and posterior bladder walls (sparing the trigone), and 0.5 ml (5 U) was injected at each site. We used a rigid cystoscope. All patients took 1 injection. Clinical, urodynamic and QOL assessments were done at 1 and 12 months after BoNT-A treatment. All patients underwent to an uroflussimetry and an urodynamic exam at 1 and 12 months after the injection. Patient Global Impression of Improvement (PGI-I) score assessed patient quality of life pre- and postoperatively. PGI-I scores were obtained at 1 and at 12 months after injections. A PGI-I score < 2 at 12 months after BoNT-A was defined as a successful treatment. Statistical analyses were conducted using SAS version 9.3 software (SAS Institute, Inc., NC). Mean values with standard deviations (±SD) were computed and reported for all items. Statistical significance was achieved if p-value was ≤0.05 (two-sides).
Mean age was of 44,2 years (range 24-56 years). The treatment with BoNT-A was successfully delivered in all 70 patients. There were no injection related complications and only 5 out of 70 patients (7,1%) had mild hematuria. Treatment was generally well tolerated. 5 out of 70 patients (7,1%) experienced postoperative uncomplicated UTI. 7 out of 70 (10%) patients (5 males and 2 females) had PVR urine volume >150 mL; 8 out of 70 (11,4%) patients (5 males and 3 females) had acute urinary retention after treatment. Overall after 1 month 59 out of 70 patients (84,3%) had a significant improvement of global urinary symptomatology and after 12 months 55 out of 70 patients (78,6%) had a significant improvement of global urinary symptomatology. Urgency disappeared in 62 out of 70 patients (88,6%) of the patients and incontinence resolved in 59 out 70 patients (84,3%) within 1 or 2 weeks after BoNT-A injections. We considered “dry” patients without any loss of urine (no pads/day) or those who used a safety pad/day. Mean maximal bladder capacity significantly increased from 248,06±47,1 to 310±58,5 milliliters (p=<0,05); mean volume at first desire to void significantly increased from 155,3±4,6 to 196,1±41,5 milliliters (p<0,05).PGI-I scores were available for 69out of 70 patients. Success rate was achieved in 51 out of 69 patients (73,9%).
Clinical experiences with BoNT-A application for OAB are still scarce and controversial, and it differs in dose, dilution, injection site, number of injections and rate. Most studies considered a low number of patients and there is a mixture of idiopathic and neurogenic detrusor overactivity. Our study showed that a dose of 100 U BoNT-A could achieve beneficial effects in a good percent of patients. We evaluated urodynamic (objective) and clinical (subjective) parameters. Urgency and incontinence significantly decreased after BoNT-A in the majority of patients. All of these objective improvement are followed by a significant impact on QOL, as based on PGI score. The side effect rate was low, and most common treatment-related complication was UTI. A limitation of this study is a short follow-up period. As a consequence we can not indicate the re-injection rate.
In the most recent guidelines, it was stated that the best alterna¬tive among the minimally invasive treatment options in NDO is BoNT-A (recommendation level A). The effectiveness of BoNT-A was supported by several randomized, placebo-controlled studies, and there was no loss in effectiveness with repeated injections. In our experience intravesical BoNT-A is an effective treatment for OAB in patients refractory to antimuscarinics. We recommended a dose of 100 UI administered as intradetrusor injections across 20 sites using a rigid cystoscope. Treatment was generally well tolerated, and most common treatment-related complications were UTI and urinary retention. We believe that it can be offered to the patients before other invasive therapeutic options.
1-Sacco E, Bientinesi R, Bassi P, Currò D. Pharmacological methods for the preclinical assessment of therapeutics for OAB: an up-to-date review. Int Urogynecol J. 2016 Feb 17. [Epub ahead of print]
2- Wagg A, Nitti VW, Kelleher C, Castro-Diaz D, Siddiqui E, Berner T Oral pharmacotherapy for overactive bladder in older patients: mirabegron as a potential alternative to antimuscarinics. Curr Med Res Opin. 2016 Feb 17:1-18. [Epub ahead of print]
3- Karsenty G, Denys P, Amarenco G, De Seze M, Gamé X, Haab F, Kerdraon J, Perrouin-Verbe B, Ruffion A, Saussine C, Soler JM, Schurch B, Chartier-Kastler E.Botulinum toxin A (Botox) intradetrusor injections in adults with neurogenic detrusor overactivity/neurogenic overactive bladder: a systematic literature review. Eur Urol. 2008 Feb;53(2):275-87. Epub 2007 Oct 16.Argomenti: incontinenza