Long-term botulinum therapy for overactive bladder: myths and reality

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

The review article presents data on the efficacy and tolerability of intravesical injections of botulinum toxin in patients with overactive bladder. The pharmacological bases of the use of botulinum therapy in this category of patients are described in detail. Data on the history of the use of botulinum toxin for medical purposes are presented. Experience to date shows that intravesical botulinum toxin injections are highly effective and well tolerated in patients with refractory overactive bladder. Botulinum therapy is included in domestic and foreign clinical guidelines as a 3rd line treatment for idiopathic and neurogenic overactive bladder. Indications for its implementation are the inefficiency and/or poor tolerability of oral pharmacotherapy. It is noted that the only botulinum toxin recommended for use in clinical practice for the treatment of overactive bladder is onabotulinumtoxin A (Botox®). The results of clinical studies are presented, showing that the effectiveness and safety of botulinum therapy do not decrease over time.

About the authors

Igor V. Kuzmin

Academician I.P. Pavlov First St. Petersburg State Medical University

Email: kuzminigor@mail.ru
ORCID iD: 0000-0002-7724-7832
SPIN-code: 2684-4070
Scopus Author ID: 56878681300
https://www.1spbgmu.ru/ru/obrazovanie/kafedry/106-glavnaya/3828-igor-valentinovich-kuzmin

Dr. Sci. (Med.), Professor of the Department of Urology

Russian Federation, L‘va Tolstogo st., Saint Petersburg, 197022

Margarita N. Slesarevskaya

Academician I.P. Pavlov First St. Petersburg State Medical University

Email: mns-1971@yandex.ru
ORCID iD: 0000-0002-4911-6018
SPIN-code: 9602-7775
Scopus Author ID: 57196117211
https://www.1spbgmu.ru/ru/universitet/strustura/kafedry/106-glavnaya/3905-slesarevskaya-margarita-nikolaevna

Cand. Sci. (Med.), Senior Researcher, Research Center of Urology of the Research Institute of Surgery and Emergency Medicine

Russian Federation, L‘va Tolstogo st., Saint Petersburg, 197022

Refat E. Amdiy

Academician I.P. Pavlov First St. Petersburg State Medical University

Email: r.e.amdiy@mail.ru
ORCID iD: 0000-0003-1305-5791
SPIN-code: 2399-7041
Scopus Author ID: 6506347944

Dr. Sci. (Med.), Professor of the Department of Urology

Russian Federation, L‘va Tolstogo st., Saint Petersburg, 197022

Tatiana V. Ulitko

Academician I.P. Pavlov First St. Petersburg State Medical University

Email: ulitko-ta@yandex.ru
ORCID iD: 0000-0002-3521-8048

Senior Laboratory Assistant, Department of Clinical Anatomy and Operative Surgery named after prof. M.G. Prives

Russian Federation, L‘va Tolstogo st., Saint Petersburg, 197022

Salman Kh. Al-Shukri

Academician I.P. Pavlov First St. Petersburg State Medical University

Author for correspondence.
Email: alshukri@mail.ru
ORCID iD: 0000-0002-4857-0542
SPIN-code: 2041-8837
Scopus Author ID: 6506423220

Doc. Sci. (Med.), Professor, Head of the Department of Urology

Russian Federation, L‘va Tolstogo st., Saint Petersburg, 197022

References

  1. Abrams P, Cardozo L, Fall M, et al. The standartisation of terminology in lower urinary tract function: Report from the standartisation sub-committee of the International Continence Society. Neurourol Urodyn. 2003;21(2):167–178. doi: 10.1002/nau.10052
  2. Irwin DE, Milsom I, Hunskaar S, et al. Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study. Eur Urol. 2006;50(6):1306–1314. doi: 10.1016/j.eururo.2006.09.019
  3. Kuzmin IV. Epidemiological aspects of overactive bladder and urge urinary incontinence. Urologicheskie vedomosti. 2015;5(3): 30–34. (In Russ.) doi: 10.17816/uroved5330-34
  4. Krivoborodov GG, Tur EI, Shirin DA. Hyperactive bladder the concept of disease and paradigms in the treatment. Medical Council. 2021;(4):121–126. (In Russ.) doi: 10.21518/2079-701X-2021-4-121-126
  5. Shormanov IS, Solovyov AS, Tyuzikov IA, Kulikov SV. Anatomical, physiological and pathophysiological features of the lower urinary tract in gender and age aspects. Urology reports (St. Petersburg). 2021;11(3):241–256. (In Russ.) doi: 10.17816/uroved70710
  6. Al-Shukri SH, Kuzmin IV, Boriskin AG, et al. Correction of microcirculatory disorders in patients with overactive bladder. Nephrology (St. Petersburg). 2011;15(1):58–64. Cited: 2022 March 04 (In Russ.)
  7. Abrams P, Kelleher CJ, Kerr LA, Rogers RG. Overactive bladder significantly affects quality of life. Am J Manag Care. 2000; 6(11 Suppl):S580–S590. Cited: 2022 March 09
  8. Al-Shukri SH, Kuzmin IV. Quality of life in patients with overactive bladder. Urologicheskie vedomosti. 2011;1(1):21–26. (In Russ.) Cited: 2022 March 04
  9. Kuzmin IV. Patogenez, klinicheskoe techenie i lechenie giperaktivnosti mochevogo puzyrya [dissertation]. Saint Petersburg; 2007. 360 p. (In Russ.)
  10. Nederzhanie mochi. Klinicheskie rekomendatsii Minzdrava RF. 2020. Available from: https://cr.minzdrav.gov.ru/recomend/8
  11. Harding CK, Lapitan MC, Arlandis S. Non-neurogenic female LUTS. Guideline of European Urological Association. 2022. Available from: https://uroweb.org/guideline/non-neurogenic-female-luts
  12. Blok B, Castro-Diaz D, Del Popolo G, et al. Neuro-Urology / Guideline of European Urological Association. 2022. Available from: https://uroweb.org/guideline/neuro-urology
  13. Kuzmin IV, Kuzmina SV. Anticholinergic therapy of an overactive bladder: clinical practice aspects. Russian Medical Inquiry. 2021;5(5): 273–279. (In Russ.) doi: 10.32364/2587-6821-2021-5-5-273-279
  14. Romikh VV, Zakharchenko AV, Kukushkina LYu, et al. Current concepts of the overactive bladder in women. Strategy for choosing drug therapy. Obstetrics and Gynecology. 2021;(8):183–191. (In Russ.) doi: 10.18565/aig.2021.8.183-191
  15. Kuzmin IV, Al-Shukri SH. Fesoterodine for the treatment of overactive bladder: pharmacological bases and clinical results. Urology reports (St. Petersburg). 2020.10(2):163–171. (In Russ.) doi: 10.17816/uroved102163-171
  16. Kulchavenya EV, Kholtobin DP. Overactive bladder in a complicated patient: which drug to choose? Urologiia. 2021;(1):120–125 (In Russ.) doi: 10.18565/urology.2021.1.120-125
  17. 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-RS2015). Neurourol Urodyn. 2017;36(4):882–893. doi: 10.1002/nau.23170
  18. Uvin P, Boudes M, Menigoz A, et al. Chronic administration of anticholinergics in rats induces a shift from muscarinic to purinergic transmission in the bladder wall. Eur Urol. 2013;64(3):502–510. doi: 10.1016/j.eururo.2013.05.031
  19. Staskin DR, MacDiarmid SA. Using anticholinergics to treat overactive bladder: the issue of treatment tolerability. Am J Med. 2006;119(3 Suppl 1):9–15. doi: 10.1016/j.amjmed.2005.12.011
  20. Coupland CAC, Hill T, Dening T, et al Anticholinergic drug exposure and the risk of dementia: a nested case-control study. JAMA Intern Med. 2019;179(8):1084–1093. doi: 10.1001/jamainternmed.2019.0677
  21. Bragg R, Hebel D, Vouri SM, Pitlick JM. Mirabegron: a beta-3 agonist for overactive bladder. Consult Pharm. 2014;29(12):823–837. doi: 10.4140/TCP.n.2014.823
  22. Whitcup SM. The History of Botulinum Toxins in Medicine: A Thousand Year Journey. Handb Exp Pharmacol. 2021;263:3–10. doi: 10.1007/164_2019_271
  23. Choudhury S, Baker MR, Chatterjee S, Kumar H. Botulinum Toxin: An Update on Pharmacology and Newer Products in Development. Toxins (Basel). 2021;13(1):58. doi: 10.3390/toxins13010058
  24. Dykstra DD, Sidi AA, Scott AB, et al. Effects of botulinum A toxin on detrusor-sphincter dyssynergia in spinal cord injury patients. J Urol. 1988;139(5):919–922. doi: 10.1016/s0022-5347(17)42717-0
  25. Schurch B, Stöhrer M, Kramer G, et al. Botulinum-A toxin for treating detrusor hyperreflexia in spinal cord injured patients: a new alternative to anticholinergic drugs? Preliminary results. J Urol. 2000;164(3 Pt 1):692–697. doi: 10.1097/00005392-200009010-00018
  26. Chapple C, Sievert KD, MacDiarmid S, et al. OnabotulinumtoxinA 100 U significantly improves all idiopathic overactive bladder symptoms and quality of life in patients with overactive bladder and urinary incontinence: a randomised, double-blind, placebo-controlled trial. Eur Urol. 2013;64(2):249–256. doi: 10.1016/j.eururo.2013.04.001
  27. Nitti VW, Dmochowski R, Herschorn S, et al. Onabotulinumtoxin A for the treatment of patients with overactive bladder and urinary incontinence: results of a phase 3, randomized, placebo controlled trial. J Urol. 2013;189(6):2186–2193. doi: 10.1016/j.juro.2012.12.022
  28. Gong QQ, Xu YQ, Xu J, et al. Meta-Analysis of Randomized Controlled Trials Using Botulinum Toxin A at Different Dosages for Urinary Incontinence in Patients With Overactive Bladder. Front Pharmacol. 2020;10:1618. doi: 10.3389/fphar.2019.01618
  29. Chohan N, Hilton P, Brown K, Dixon L. Efficacy and duration of response to botulinum neurotoxin A (onabotulinumA) as a treatment for detrusor overactivity in women. Int Urogynecol J. 2015;26(11):1605–1612. doi: 10.1007/s00192-015-2751-4
  30. Apostolidis A, Dasgupta P, Fowler CJ. Proposed mechanism for the efficacy of injected botulinum toxin in the treatment of human detrusor overactivity. Eur Urol. 2006;49(4):644–560. doi: 10.1016/j.eururo.2005.12.010
  31. Dan Spinu A, Gabriel Bratu O, Cristina Diaconu C, et al. Botulinum toxin in low urinary tract disorders – over 30 years of practice (Review). Exp Ther Med. 2020;20(1):117–120. doi: 10.3892/etm.2020.8664
  32. Krivoborodov GG, Vasiliev AV, Shumilo DV, et al. Botulinum toxin type A in patients with overactive bladder. Urologiya. 2010;(3):36–40. (In Russ.)
  33. Arkhireev AS, Romikh VV, Panteleyev VV, et al. The efficacy of therapy in patients with neurogenic and idiopathic detrusor hyperactivity depending on the dose of botulinum toxin type A. Experimental and Clinical Urology. 2017;(3):98–103. (In Russ.)
  34. Filippova ЕS, Bazhenov IV, Zyrjanov AV, et al. Clinical effectiveness of intradetrusor injections of botulinum toxin type a in dose 100 units in multiple sclerosis patients with neurogenic detrusor overactivity. Urology reports (St. Petersburg). 2020;10(1):25–32. (In Russ.) doi: 10.17816/uroved10125-32
  35. Al-Shukri SH, Kuzmin IV, Slesarevskaya MN, Ignashov YuA. Botulinum toxin type A in the treatment of bladder pain syndrome in women: initial results. Urologicheskie vedomosti. 2018;8(2):5–10. (In Russ.) doi: 10.17816/uroved825-10
  36. Nitti VW, Ginsberg D, Sievert KD, et al. Durable Efficacy and Safety of Long-Term OnabotulinumtoxinA Treatment in Patients with Overactive Bladder Syndrome: Final Results of a 3.5-Year Study. J Urol. 2016;196(3):791–800. doi: 10.1016/j.juro.2016.03.146
  37. Rovner E, Kohan A, Chartier-Kastler E, et al. Long-Term Efficacy and Safety of OnabotulinumtoxinA in Patients with Neurogenic Detrusor Overactivity Who Completed 4 Years of Treatment. J Urol. 2016;196(3):801–808. doi: 10.1016/j.juro.2016.04.046
  38. Datta SN, Roosen A, Pullen A, et al. Immunohistochemical expression of muscarinic receptors in the urothelium and suburothelium of neurogenic and idiopathic overactive human bladders, and changes with botulinum neurotoxin administration. J Urol. 2010;184(6):2578–2585. doi: 10.1016/j.juro.2010.07.034
  39. Elbaset MA, Taha DE, El-Hefnawy AS, et al. Assessment of Anticholinergic Use After Fading of BTX-A Effects in Refractory Idiopathic Overactive Bladder: A Prospective Blinded Randomized Trial. Int Neurourol J. 2019;23(3):240–248. doi: 10.5213/inj.1938098.049
  40. Compérat E, Reitz A, Delcourt A, et al. Histologic features in the urinary bladder wall affected from neurogenic overactivity – a comparison of inflammation, oedema and fibrosis with and without injection of botulinum toxin type A. Eur Urol 2006;50:1058–1064. doi: 10.1016/j.eururo.2006.01.025
  41. Temeltas G, Tikiz C, Dagci T, et al. The effects of botulinum-A toxin on bladder function and histology in spinal cord injured rats: is there any difference between early and late application? J Urol. 2005;174:2393–2396. doi: 10.1097/01.ju.0000180410.78774.b5
  42. Pascali MP, Mosiello G, Boldrini R, et al. Effects of botulinum toxin type A in the bladder wall of children with neurogenic bladder dysfunction: a comparison of histological features before and after injections. J Urol. 2011;185(6 Suppl):2552–2557. doi: 10.1016/j.juro.2011.01.019
  43. Apostolidis A, Jacques TS, Freeman A, et al. Histological changes in the urothelium and suburothelium of human overactive bladder following intradetrusor injections of botulinum neurotoxin type A for the treatment of neurogenic or idiopathic detrusor overactivity. Eur Urol. 2008;53(6):1245–1253. doi: 10.1016/j.eururo.2008.02.037
  44. Haferkamp A, Schurch B, Reitz A, et al. Lack of ultrastructural detrusor changes following endoscopic injection of botulinum toxin type A in overactive neurogenic bladder. Eur Urol. 2004;46(6): 784–791. doi: 10.1016/j.eururo.2004.07.011
  45. Fasano G, Grimaldi L, Nisi G, et al. The Regenerative Effects of Botulinum Toxin A: New Perspectives. J Invest Surg. 2022:1–2. doi: 10.1080/08941939.2021.2008553
  46. Vince R, Tracey A, Deebel NA, et al. Effects of vesical and perfusion pressure on perfusate flow, and flow on vesical pressure, in the isolated perfused working pig bladder reveal a potential mechanism for the regulation of detrusor compliance. Neurourol Urodyn. 2017;37(2):642–649. doi: 10.1002/nau.23362
  47. Jia C, Xing T, Shang Z, et al. Botulinum toxin A improves neurogenic bladder fibrosis by suppressing transforming growth factor β1 expression in rats. Transl Androl Urol. 2021;10(5):2000–2007. doi: 10.21037/tau-21-62
  48. Jiang YH, Ong HL, Kuo HC. Predictive factors of adverse events after intravesical suburothelial onabotulinumtoxina injections for overactive bladder syndrome-A real-life practice of 290 cases in a single center. Neurourol Urodyn. 2017;36(1):142–147. doi: 10.1002/nau.22892
  49. Hamid R, Lorenzo-Gomez MF, Schulte-Baukloh H, et al. Onabotulinumtoxin A is a well tolerated and effective treatment for refractory overactive bladder in real-world practice. Int Urogynecol J. 2021;32(1):65–74. doi: 10.1007/s00192-020-04423-0
  50. Bickhaus JA, Vaughan M, Truong T, et al. A comparison of antibiotic prophylaxis regimens to decrease the risk of post-procedure urinary tract infection after onabotulinum toxin A injection. Int Urogynecol J. 2020;31(9):1907–1912. doi: 10.1007/s00192-020-04230-7
  51. Bickhaus JA, Bradley MS, Amundsen CL, et al. Does a Recent Urinary Tract Infection Increase the Risk of Postprocedure Urinary Tract Infection After Onabotulinum Toxin A? Female Pelvic Med Reconstr Surg. 2021;27(2):121–125. doi: 10.1097/SPV.0000000000000753
  52. Visco AG, Brubaker L, Richter HE, et al. Anticholinergic therapy vs. onabotulinumtoxinA for urgency urinary incontinence. N Engl J Med. 2012;367(19):1803–1813. doi: 10.1056/NEJMoa1208872
  53. Amundsen CL, Richter HE, Menefee SA, et al. OnabotulinumtoxinA vs Sacral Neuromodulation on Refractory Urgency Urinary Incontinence in Women: A Randomized Clinical Trial. JAMA. 2016;316(13):1366–1374. doi: 10.1001/jama.2016.14617
  54. Herschorn S, Kohan A, Aliotta P, et al. The efficacy and safety of onabotulinumtoxinA or solifenacin compared with placebo in solifenacin naïve patients with refractory overactive bladder: results from a multicenter, randomized, double-blind phase 3b trial. J Urol. 2017;198(1):167–175. doi: 10.1016/j.juro.2017.01.06
  55. Patel DN, Jamnagerwalla J, Houman J, et al. What is the true catheterization rate after intravesical onabotulinumtoxinA injection? Int Urogynecol J. 2018;29(7):1005–1009. doi: 10.1007/s00192-017-3440-2
  56. Marcelissen TA, Rahnama’i MS, Snijkers A, et al. Long-term follow-up of intravesical botulinum toxin-A injections in women with idiopathic overactive bladder symptoms. World J Urol. 2017;35(2): 307–311. doi: 10.1007/s00345-016-1862-y
  57. Osborn DJ, Kaufman MR, Mock S, et al. Urinary retention rates after intravesical onabotulinumtoxinA injection for idiopathic overactive bladder in clinical practice and predictors of this outcome. Neurourol Urodyn. 2015;34:675–678. doi: 10.1002/nau.22642
  58. Miotla P, Cartwright R, Skorupska K, et al. Urinary retention in female OAB after intravesical Botox injection: who is really at risk? Int Urogynecol J. 2017;28(6):845–850. doi: 10.1007/s00192-016-3212-4

Copyright (c) 2022 Eco-Vector


 


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies