Salvage Combination Therapies for Refractory Overactive Bladder
- 23 Downloads
Purpose of Review
With a high prevalence of overactive bladder (OAB) worldwide and rising health care costs for patients who fail first-, second-, and third-line treatments, there is a growing need to explore novel strategies to address the most refractory cases of OAB. The concept of utilizing combination treatment regimens to maximize efficacy while minimizing morbidity and side effects, in a cost-effective manner, is discussed in this review article.
A literature review over the last 10 years was performed, focusing on therapies used in combination for OAB including behavioral therapy, pharmacologic therapy, neuromodulation, and botulinum toxin. A separate literature review specifically for augmentation cystoplasty was also undertaken. Such “salvage” treatments suggested in the literature include pharmacologic therapy in combination or with behavioral modification, various forms of neuromodulation with medication, alternative forms of neuromodulation, with or without prior botulinum toxin injections, and lastly, augmentation cystoplasty.
In this review article, we outline combination therapies such as adding mirabegron to solifenacin, anticholinergic medication in addition to either behavioral therapy or various types of neuromodulation and using neuromodulation after failed botulinum toxin injections are efficacious treatment approaches and have shown to be superior to monotherapy for the treatment non-neurogenic refractory OAB. In the most severe cases of refractory OAB, augmentation cystoplasty remains an option that provides acceptable results in the appropriately selected patient.
KeywordsOveractive bladder Anticholinergics Mirabegron Salvage therapy Neuromodulation Augmentation cystoplasty
Compliance with Ethical Standards
Conflict of Interest
Sarah Martin declares that she has no conflict of interest.
Esther Han declares that she has no conflict of interest.
Jason Gilleran declares that he has no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 2.Coyne KS, Wein A, Nicholson S, Kvasz M, Chen CI, Milsom I. Economic burden of urgency urinary incontinence in the United States: a systematic review. J Manag Care Pharm. 2014;20:130–40. Available at: http://www.jmcp.org/doi/10.18553/jmcp.2014.20.2.130. Accessed 7 June 2018.PubMedGoogle Scholar
- 3.Ganz ML, Smalarz AM, Krupski TL, et al. Economic costs of overactive bladder in the United States. Urol. 2010;75:526–532.e18 Available at: http://linkinghub.elsevier.com/retrieve/pii/S0090429509023115. Accessed 1 July 2018.
- 4.•• Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU Guideline. J Urol. 2012;188:2455–2463. Available at: http://linkinghub.elsevier.com/retrieve/pii/S0022534712049592. Accessed 13 Aug 2018. Current guideline for OAB treatment.
- 5.•• Apostolidis A, Averbeck MA, Sahai A, et al. Can we create a valid treatment algorithm for patients with drug resistant overactive bladder (OAB) syndrome or detrusor overactivity (DO)? Results from a think tank (ICI-RS 2015). Neurourol Urodyn. 2017;36:882–893. Available at: https://onlinelibrary.wiley.com/doi/abs/10.1002/nau.23170. Accessed 8 Apr 2018. First attempt to create a treatment algorithm for patients with OAB. It discusses AM failures, combination pharmacologic therapy, Botox vs neuromodulation, and augmentation cyoplasty—all of which is discussed in this review article.
- 6.American Urological Association. Available at: https://www.auanet.org/guidelines/incontinence-non-neurogenic-overactive-bladder-(2012-amended-2014). Accessed 30 Sept 2018.
- 7.Quirouet A, Goldman HB. Management of overactive bladder refractory to medical therapy. Current Bladder Dysfunction Reports. 2014;9:336–40 Available at: http://link.springer.com/10.1007/s11884-014-0259-2, Accessed 1 July 2018.CrossRefGoogle Scholar
- 8.• Chancellor MB, Yehoshua A, Waweru C, et al. Limitations of anticholinergic cycling in patients with overactive bladder (OAB) with urinary incontinence (UI): results from the CONsequences of Treatment Refractory Overactive bLadder (CONTROL) study. Int Urol Nephrol. 2016;48:1029–1036. Available at: http://link.springer.com/10.1007/s11255-016-1277-0. Accessed 2 July 2018. Results suggest that changing between various AM medications does not improve efficacy of OAB treatment.
- 9.Komesu YM, Amundsen CL, Richter HE, et al. Refractory urgency urinary incontinence treatment in women: impact of age on outcomes and complications. Am J Obstet Gynecol. 2018;218:111.e1–9 Available at: http://linkinghub.elsevier.com/retrieve/pii/S0002937817311882. Accessed 15 July 2018.CrossRefGoogle Scholar
- 10.Abrams P, Kelleher C, Staskin D, Rechberger T, Kay R, Martina R, et al. Combination treatment with mirabegron and solifenacin in patients with overactive bladder: efficacy and safety results from a randomised, double-blind, dose-ranging, phase 2 study (symphony). Eur Urol. 2015;67:577–88 Available at: http://linkinghub.elsevier.com/retrieve/pii/S0302283814001316. Accessed 2 July 2018.CrossRefGoogle Scholar
- 11.Yamaguchi O, Kakizaki H, Homma Y, et al. Safety and efficacy of mirabegron as ‘add-on’ therapy in patients with overactive bladder treated with solifenacin: a post-marketing, open-label study in Japan (MILAI study). BJU Int. 116:612–622. Available at: https://onlinelibrary.wiley.com/doi/abs/10.1111/bju.13068. Accessed 2 July 2018.
- 12.•• Drake MJ, Chapple C, Esen AA, et al. Efficacy and safety of mirabegron add-on therapy to solifenacin in incontinent overactive bladder patients with an inadequate response to initial 4-week solifenacin monotherapy: a randomised double-blind multicentre phase 3b study (BESIDE). Eur Urol. 2016;70:136–145. Available at: http://linkinghub.elsevier.com/retrieve/pii/S0302283816002074. Accessed 2 July 2018. Shows the evidence to suggest the superior efficacy of combination pharmacologic therapy using an AM and beta-3 agonist compared to AM monotherapy.
- 13.Yu YF, Nichol MB, Yu AP, Ahn J. Persistence and adherence of medications for chronic overactive bladder/urinary incontinence in the California Medicaid Program. Value Health. 2005;8:495–505 Available at: http://linkinghub.elsevier.com/retrieve/pii/S1098301510600435. Accessed 9 July 2018.CrossRefGoogle Scholar
- 14.Burgio KL, Kraus SR, Menefee S, Borello-France D, Corton M, Johnson HW, et al. Behavior therapy to enable drug discontinuation in the treatment of urge incontinence: a randomized controlled trial. Ann Intern Med. 2008;149:161–9 Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201984/. Accessed 1 July 2018.CrossRefGoogle Scholar
- 15.Souto SC, Reis LO, Palma T, Palma P, Denardi F. Prospective and randomized comparison of electrical stimulation of the posterior tibial nerve versus oxybutynin versus their combination for treatment of women with overactive bladder syndrome. World J Urol. 2014;32:179–84 Available at: http://link.springer.com/10.1007/s00345-013-1112-5. Accessed 9 July 2018.CrossRefGoogle Scholar
- 16.Tang H, Chen J, Wang Y, et al. Combination of sacral neuromodulation and tolterodine for treatment of idiopathic overactive bladder in women: a clinical trial. Urol J. 2014;11:1800–1805Google Scholar
- 17.Li X, Liao L, Chen G, Wang Z, Deng H. Combination of sacral nerve and tibial nerve stimulation for treatment of bladder overactivity in pigs. Int Urol Nephrol. 2017;49:1139–45 Available at: http://link.springer.com/10.1007/s11255-017-1587-x. Accessed 15 July 2018.CrossRefGoogle Scholar
- 18.• Vecchioli-Scaldazza C, Morosetti C. Effectiveness and durability of solifenacin versus percutaneous tibial nerve stimulation versus their combination for the treatment of women with overactive bladder syndrome: a randomized controlled study with a follow-up of ten months. Int Braz J Urol. 2018;44:102–108. Available at: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1677-55382018000100102&lng=en&tlng=en. Accessed 15 July 2018. Provides evidence to suggest the superiority of combination therapy with PTNS and solifenacin vs either monotherapy alone.
- 19.Pham K, Guralnick ML, O’Connor RC. Unilateral versus bilateral stage I neuromodulator lead placement for the treatment of refractory voiding dysfunction. Neurourol Urodyn. 27:779–81 Available at: https://onlinelibrary.wiley.com/doi/abs/10.1002/nau.20577. Accessed 15 July 2018.
- 20.Marcelissen TAT, Leong RK, Serroyen J, van Kerrebroeck PEV, de Wachter SGG. The use of bilateral sacral nerve stimulation in patients with loss of unilateral treatment efficacy. J Urol. 2011;185:976–80 Available at: http://linkinghub.elsevier.com/retrieve/pii/S0022534710049669. Accessed 15 July 2018.CrossRefGoogle Scholar
- 22.El-Azab AS, Siegel SW. Specific tips for general controversies in sacral Neuromodulation. Curr Urol Rep. 2016;17. Available at: http://link.springer.com/10.1007/s11934-016-0640-0. Accessed 15 July 2018:79.CrossRefGoogle Scholar
- 23.• Amundsen CL, Komesu YM, Chermansky C, et al. Two-year outcomes of sacral neuromodulation versus onabotulinumtoxina for refractory urgency urinary incontinence: a randomized trial. Eur Urol. 2018. Results suggest no evidence of superiority between intradetrusor Botox injections and sacral neuromodulation for the treatment of OAB. Provides pros and cons of both treatment. Google Scholar
- 24.Dowson C, Watkins J, Khan MS, Dasgupta P, Sahai A. Repeated botulinum toxin type a injections for refractory overactive bladder: medium-term outcomes, safety profile, and discontinuation rates. Eur Urol. 2012;61:834–9 Available at: http://linkinghub.elsevier.com/retrieve/pii/S030228381101373X. Accessed Aug 14 2018.CrossRefGoogle Scholar
- 25.•• Hoag N, Plagakis S, Pillay S, et al. Sacral neuromodulation for refractory overactive bladder after prior intravesical onabotulinumtoxin A treatment. Neurourol Urodyn 36:1377–1381. Available at: https://onlinelibrary.wiley.com/doi/abs/10.1002/nau.23117. Accessed 15 July 2018. Provides evidence that sacral neuromodulation can still provide symptomatic relief in patients who fail previous intradetrusor Botox injections.
- 29.Department of Health, UK. Hospital Episode Statistics. Department of Health, UK.Google Scholar
- 31.Herbison GP, Arnold EP. Sacral neuromodulation with implanted devices for urinary storage and voiding dysfunction in adults. Cochrane Database Syst Rev. 2009: CD004202. Available at: https://www.ncbi.nlm.nih.gov/pubmed/19370596.
- 32.de Figueiredo AA, Lucon AM, Srougi M. Bladder augmentation for the treatment of chronic tuberculous cystitis. Clinical and urodynamic evaluation of 25 patients after long term follow-up. Neurourol Urodyn. 2006;25:433–40 Available at: https://www.ncbi.nlm.nih.gov/pubmed/16791845.CrossRefGoogle Scholar