By Chiara Ghetti, MD
Associate Professor,
Obstetrics and Gynecology,
Division of Female Pelvic Medicine and Reconstructive Surgery,
Washington University School of Medicine,
St. Louis, MO
Dr. Ghetti reports no financial relationships relevant to this field of study.
Synopsis: Intradetrusor onabotulinumtoxinA may be a second-line treatment option for overactive bladder in appropriate patients. Health care providers should thoroughly counsel patients on risks and adverse events associated with onabotulinumtoxinA toxin injections.
Source: American Urogynecologic Society and American College of Obstetricians and Gynecologists. Committee opinion: OnabotulinumtoxinA and the bladder. Female Pelvic Med Reconstr Surg 2014;20:245-247.
This joint Committee Opinion of the American College of Obstetricians and Gynecologists and the American Urogynecologic Society discusses the use of onabotulinumtoxinA for the treatment of overactive bladder (OAB). The FDA approved onabotulinumtoxinA for cystoscopic injection in the detrusor muscle for the treatment of neurogenic bladder in 2011 and for the treatment of OAB in January 2013. The use of botulinum toxin in the bladder has been associated with a significant improvement in OAB symptoms. Intradetrusor onabotulinumtoxinA injections may be a second-line treatment option for OAB in appropriate patients after comprehensive counseling. Shared decision-making between patient and provider should include discussion of contraindications, risks, benefits, and post-procedural adverse events, which include the risk of post-procedure urinary retention, urinary tract infections, hematuria, pain, and transient body weakness. Providers who perform onabotulinumtoxinA injections must have appropriate training and experience in treating women with pelvic floor disorders, operative cystoscopy privileges, and the ability to diagnose and manage any adverse outcomes after onabotulinumtoxinA injections into the bladder.
Commentary
The International Continence Society has defined OAB as a bladder syndrome that includes, “urinary urgency, usually accompanied by frequency and nocturia, with or without urgency incontinence, in the absence of urinary tract infection or other obvious pathology.”1 Urinary urgency is the sudden and compelling desire to pass urine, which is difficult to defer, while urinary frequency is the perception of having to void too many times during the day. Nocturia is defined as having to wake up once or more per night to void.2 The prevalence of OAB in women is estimated to be as high as 30%, and the prevalence of OAB increases with age in both men and women. OAB has a significant impact on women’s quality of life. Many women experience embarrassment, social isolation, decrease in physical activity and sexual intimacy, as well as decreased productivity. OAB has been associated with depressive symptoms3 and is an independent risk factor for falls since nocturia is common.4 OAB also has a large societal impact, and in 2009, it was estimated that more than $24.9 billion was spent on OAB.5
The American Urologic Association (AUA) and the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction (SUFU) approved guidelines for the diagnosis and treatment of OAB in 2012.6 The treatment options are divided in first-, second-, and third-line treatments. First-line therapy for all patients with OAB should include education about lower urinary tract function and behavioral therapies that include fluid management, bladder training, and pelvic floor muscle training. These behavioral therapies may be combined with antimuscarinic therapies, which are considered second-line treatments and include, in alphabetical order, darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, or trospium. A different antimuscarinic can be used if patients experience inadequate symptom relief or unacceptable side effects. Antimuscarinics are contraindicated in patients with narrow angle glaucoma and should be used with caution in elderly or frail patients, patients with delayed gastric emptying or urinary retention, or patients already using other anticholinergic medications. The medical management of OAB may need to undergo some modifications as we gain more information about the long-term effects of anticholinergic use. In a recent article published in JAMA Internal Medicine, the authors report that higher cumulative anticholinergic use is associated with an increased risk for dementia based on a prospective population-based cohort study.7
Third-line treatment for OAB includes sacral neuromodulation. OnabotulinumtoxinA, a second-line treatment, has been FDA approved since the publication of the AUA/SUFU guidelines. The randomized, controlled trial reported by Visco et al supports the use of onabotulinumtoxinA as a second-line treatment.8 In this double-blind, double-placebo-controlled, randomized trial involving women with idiopathic urgency urinary incontinence, patients were assigned to either daily oral anticholinergic medication plus one intradetrusor injection of saline or one intradetrusor injection of 100 U of onabotulinumtoxinA plus daily oral placebo. In the 247 women treated, similar reductions in daily episodes of urgency incontinence were seen in subjects treated with oral anticholinergic therapy and those treated with onabotulinumtoxinA by injection. The group treated with onabotulinumtoxinA was less likely to have dry mouth side effects and more likely to have complete resolution of urgency urinary incontinence than the group treated with anticholinergic medications. However, the group treated with onabotulinumtoxinA had higher rates of transient urinary retention and urinary tract infections.
Botulinum toxin is a powerful neurotoxin derived from the anaerobic bacterium Clostridium botulinum. There are seven types of toxin, labeled A-G. Botulinum toxin acts as a muscle paralytic by inhibiting the release of acetylcholine from presynaptic vesicles from motor neurons at the neuromuscular junction. The literature regarding the use of botulinum toxin onabotulinumtoxinA for overactive bladder has been reviewed in a Cochrane review.9 There is clear level I evidence to support the use of botulinum toxin as an effective and safe therapy in women with neurogenic and idiopathic urge incontinence.
Use of onabotulinumtoxinA is contraindicated in patients with known hypersensitivity to onabotulinumtoxinA, dysphagia, preexisting neuromuscular disorders (myasthenia gravis), and compromised respiratory status. There are no adequate and well-controlled studies in pregnant women, and it is considered an FDA Pregnancy Category C drug.
Candidates for onabotulinumtoxinA should be counseled about its risks and the possibility of post-procedure adverse events, including urinary retention, urinary tract infection, hematuria, and weakness. Patients should have close post-procedure follow-up to assess the effectiveness of the injection and an in-office evaluation of bladder emptying. Only clinicians who are trained in treating women with pelvic floor disorders, who have operative cystoscopy privileges, and who have the ability to diagnose and manage any post-procedure adverse events should perform onabotulinumtoxinA injections. Many subspecialists in female pelvic medicine and reconstructive surgery and urologists are qualified to inject onabotulinumtoxinA for OAB.
References
- Haylen BT, et al. An International Urogynecology Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Neurourol Urodyn 2010;29:4-20.
- Abrams P, et al; Standardisation Sub-committee of the International Continence Society. The standardisation of terminology of lower urinary tract function: Report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn 2002;21:167-178.
- Melville JL, et al. Incontinence severity and major depression in incontinent women. Obstet Gynecol 2005;106:585-592.
- Brown JS, et al. Urinary incontinence: Does it increase risk for falls and fractures? Study of Osteoporotic Fractures Research Group. J Am Geriatr Soc 2000;48:721-725.
- Onukwugha E, et al. The total economic burden of overactive bladder in the United States: A disease-specific approach. Am J Manag Care 2009;15:S90-97.
- Gormley EA, et al; American Urological Association; Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. J Urol 2012;188(6 Suppl):2455-2463.
- Gray SL, et al. Cumulative use of strong anticholinergics and incident dementia: A prospective cohort study. JAMA Intern Med 2015;175:401-407.
- Visco AG, et al. Anticholinergic therapy vs. onabotulinumtoxina for urgency urinary incontinence. N Engl J Med 2012;367:1803-1813.
- Madhuvrata P, et al. Which anticholinergic drug for overactive bladder symptoms in adults. Cochrane Database Syst Rev 2012;Jan 18:CD005429.
ABSTRACT & COMMENTARY: Healthcare providers should thoroughly counsel patients on the risks associated with onabotulinumtoxinA toxin injections.
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