Current Urology Reports

, Volume 14, Issue 3, pp 227–234 | Cite as

Botulinum Toxin—What Urologic Uses Does the Data Support?

Female Urology (H Goldman, Section Editor)

Abstract

Botulinum toxin-A (BTX-A) is well established in the management of various aspects of lower urinary tract dysfunction (LUTD). One formulation, OnabotulinumtoxinA has recently been licensed in many parts of the world for use in neurogenic detrusor overactivity (NDO), and in the US for idiopathic overactive bladder (OAB), in patient’s refractory to antimuscarinics. This review article looks at recent clinical publications that examine the use of BTX-A for the treatment of LUTD with a focus on OAB, detrusor overactivity (DO), benign prostatic hyperplasia (BPH) and Painful bladder syndrome / interstitial cystitis (PBS / IC). A literature review was conducted using the PubMed database and studies that were published within the time frame of January 2011 to present were included. Large randomised placebo controlled trials and a pooled analysis of patients with multiple sclerosis / spinal cord injury and NDO has suggested that BTX-A improved urinary incontinence (UI) episodes, urodynamic parameters and QoL in these patients. 200 U of OnabotulinumtoxinA appeared equivalent to 300 U. In patients with OAB, lower doses of 100 U OnabotulinumtoxinA, appear efficacious and with an acceptable adverse event profile. In one large phase III trial, de novo clean intermittent catheterisation rates were 6.1 %. Repeated injections in DO appear efficacious. Results from BPH studies are mixed, and the largest randomised study in this setting has shown significant improvements in a number of parameters for a variety of OnabotulinumtoxinA doses, but none of the doses were statistically better than placebo. Few studies have been conducted in PBS / IC and larger scale randomised placebo controlled trials are required to validate its use in this setting.

Keywords

Detrusor overactivity Overactive bladder Painful bladder syndrome Interstitial cystitis Benign prostatic hyperplasia Botulinum toxin A 

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Abrams P, Andersson KE, Birder L, Brubaker L, Cardozo L, Chapple C, et al. Fourth International Consultation on Incontinence Recommendations of the International Scientific Committee: evaluation and treatment of urinary incontinence, pelvic organ prolapse, and fecal incontinence. Neurourol Urodyn. 2010;29(1):213–40.PubMedCrossRefGoogle Scholar
  2. 2.
    Lucas MG, Bosch RJ, Burkhard FC, Cruz F, Madden TB, Nambiar AK, et al. EAU guidelines on surgical treatment of urinary incontinence. Eur Urol. 2012;62(6):1118–29.PubMedCrossRefGoogle Scholar
  3. 3.
    • Cruz F, Herschorn S, Aliotta P, Brin M, Thompson C, Lam W, et al. Efficacy and safety of onabotulinumtoxinA in patients with urinary incontinence due to neurogenic detrusor overactivity: a randomised, double-blind, placebo-controlled trial. Eur Urol. 2011;60(4):742–50. Large phase III RCT in NDO pts with MS and SCI showing good efficacy for 200 and 300 U OnabotulinumtoxinA..PubMedCrossRefGoogle Scholar
  4. 4.
    • Ginsberg D, Gousse A, Keppenne V, Sievert KD, Thompson C, Lam W, et al. Phase III efficacy and tolerability study of onabotulinumtoxinA for urinary incontinence from neurogenic detrusor overactivity. J Urol. 2012;187(6):2131–9. Large phase III multi-centre RCT of NDO pts with MS and SCI showing good efficacy of 200 and 300 U OnabotulinumtoxinA..PubMedCrossRefGoogle Scholar
  5. 5.
    Rovner E, Dmochowski R, Chapple C, Thompson C, Lam W, Haag-Molkenteller C. OnabotulinumtoxinA improves urodynamic outcomes in patients with neurogenic detrusor overactivity. Neurourol Urodyn. 2013. doi:10.1002/nau.22376.PubMedGoogle Scholar
  6. 6.
    Herschorn S, Gajewski J, Ethans K, Corcos J, Carlson K, Bailly G, et al. Efficacy of botulinum toxin A injection for neurogenic detrusor overactivity and urinary incontinence: a randomized, double-blind trial. J Urol. 2011;185(6):2229–35.PubMedCrossRefGoogle Scholar
  7. 7.
    Deffontaines-Rufin S, Weil M, Verollet D, Peyrat L, Amarenco G. Botulinum toxin A for the treatment of neurogenic detrusor overactivity in multiple sclerosis patients. Int Braz J Urol. 2011;37(5):642–8.PubMedCrossRefGoogle Scholar
  8. 8.
    • Kennelly M, Dmochowski R, Ethans K, Karsenty G, Schulte-Baukloh H, Jenkins B, et al. Long-term efficacy and safety of onabotulinumtoxinA in patients with urinary incontinence Due to neurogenic detrusor overactivity: an interim analysis. Urology. 2013;81(3):491–7. Efficacy of repeated injections of BTX-A in NDO patients..PubMedCrossRefGoogle Scholar
  9. 9.
    Hikita K, Honda M, Kawamoto B, Panagiota T, Inoue S, Hinata N, et al. Botulinum toxin type A injection for neurogenic detrusor overactivity: clinical outcome in Japanese patients. Int J Urol. 2013;20(1):94–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Khan S, Game X, Kalsi V, Gonzales G, Panicker J, Elneil S, et al. Long-term effect on quality of life of repeat detrusor injections of botulinum neurotoxin-A for detrusor overactivity in patients with multiple sclerosis. J Urol. 2011;185(4):1344–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Giannantoni A, Conte A, Proietti S, Giovannozzi S, Rossi A, Fabbrini G, et al. Botulinum toxin type A in patients with Parkinson's disease and refractory overactive bladder. J Urol. 2011;186(3):960–4.PubMedCrossRefGoogle Scholar
  12. 12.
    Sussman D, Patel V, Del Popolo G, Lam W, Globe D, Pommerville P. Treatment satisfaction and improvement in health-related quality of life with onabotulinumtoxinA in patients with urinary incontinence due to neurogenic detrusor overactivity. Neurourol Urodyn. 2013;32(3):242–9.Google Scholar
  13. 13.
    Kuo HC, Liu SH. Effect of repeated detrusor onabotulinumtoxinA injections on bladder and renal function in patients with chronic spinal cord injuries. Neurourol Urodyn. 2011;30(8):1541–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Jia C, Liao LM, Chen G, Sui Y. Detrusor botulinum toxin A injection significantly decreased urinary tract infection in patients with traumatic spinal cord injury. Spinal Cord. 2013. doi:10.1038/sc.2012.180.
  15. 15.
    • Nitti VW, Dmochowski R, Herschorn S, Sand P, Thompson C, Nardo C et al. OnabotulinumtoxinA for the Treatment of Patients with Overactive Bladder and Urinary Incontinence: Results of a Phase III Randomized Placebo-Controlled Trial. J Urol. 2012. doi:10.1016/j.juro.2012.12.022. Large phase III RCT assessing OnabotulinumtoxinA at 100 U verus placebo.
  16. 16.
    Visco AG, Brubaker L, Richter HE, Nygaard I, Paraiso MF, Menefee SA, et al. Anticholinergic therapy vs. onabotulinumtoxina for urgency urinary incontinence. N Engl J Med. 2012;367(19):1803–13.PubMedCrossRefGoogle Scholar
  17. 17.
    Fowler CJ, Auerbach S, Ginsberg D, Hale D, Radziszewski P, Rechberger T, et al. 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. Eur Urol. 2012;62(1):148–57.PubMedCrossRefGoogle Scholar
  18. 18.
    Rovner E, Kennelly M, Schulte-Baukloh H, Zhou J, Haag-Molkenteller C, Dasgupta P. Urodynamic results and clinical outcomes with intradetrusor injections of onabotulinumtoxinA in a randomized, placebo-controlled dose-finding study in idiopathic overactive bladder. Neurourol Urodyn. 2011;30(4):556–62.PubMedCrossRefGoogle Scholar
  19. 19.
    Tincello DG, Kenyon S, Abrams KR, Mayne C, Toozs-Hobson P, Taylor D, et al. Botulinum toxin a versus placebo for refractory detrusor overactivity in women: a randomised blinded placebo-controlled trial of 240 women (the RELAX study). Eur Urol. 2012;62(3):507–14.PubMedCrossRefGoogle Scholar
  20. 20.
    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(4):834–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Game X, Khan S, Panicker JN, Kalsi V, Dalton C, Elneil S, et al. Comparison of the impact on health-related quality of life of repeated detrusor injections of botulinum toxin in patients with idiopathic or neurogenic detrusor overactivity. BJU Int. 2011;107(11):1786–92.PubMedCrossRefGoogle Scholar
  22. 22.
    Granese R, Adile G, Gugliotta G, Cucinella G, Saitta S, Adile B. Botox((R)) for idiopathic overactive bladder: efficacy, duration and safety. Effectiveness of subsequent injection. Arch Gynecol Obstet. 2012;286(4):923–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Mohee A, Khan A, Harris N, Eardley I. Long-term outcome of the use of intravesical botulinum toxin for the treatment of overactive bladder (OAB). BJU Int. 2013;111(1):106–13.PubMedCrossRefGoogle Scholar
  24. 24.
    Sahai A, Kalsi V, Khan MS, Fowler CJ. Techniques for the intradetrusor administration of botulinum toxin. BJU Int. 2006;97(4):675–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Manecksha RP, Cullen IM, Ahmad S, McNeill G, Flynn R, McDermott TE, et al. Prospective randomised controlled trial comparing trigone-sparing versus trigone-including intradetrusor injection of abobotulinumtoxinA for refractory idiopathic detrusor overactivity. Eur Urol. 2012;61(5):928–35.PubMedCrossRefGoogle Scholar
  26. 26.
    Alloussi SH, Lang C, Eichel R, Al-Kaabneh A, Seibold J, Schwentner C, et al. Videourodynamic changes of botulinum toxin A in patients with neurogenic bladder dysfunction (NBD) and idiopathic detrusor overactivity (IDO) refractory to drug treatment. World J Urol. 2012;30(3):367–73.PubMedCrossRefGoogle Scholar
  27. 27.
    Krhut J, Samal V, Nemec D, Zvara P. Intradetrusor versus suburothelial onabotulinumtoxinA injections for neurogenic detrusor overactivity: a pilot study. Spinal Cord. 2012;50(12):904–7.PubMedCrossRefGoogle Scholar
  28. 28.
    • Kuo H-C. Bladder base/trigone injection is safe and as effective as bladder body injection of OnabotulinumtoxinA for idiopathic detrusor overactivity refractory to antimuscarinics. Neurourol Urodyn. 2011;30(7):1242–8. Open label study assessing different BTX-A injection techniques in the bladder..PubMedGoogle Scholar
  29. 29.
    Padmanabhan P, Scarpero HM, Milam DF, Dmochowski RR, Penson DF. Five-year cost analysis of intra-detrusor injection of botulinum toxin type A and augmentation cystoplasty for refractory neurogenic detrusor overactivity. World J Urol. 2011;29(1):51–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Leong RK, de Wachter SG, Joore MA, van Kerrebroeck PE. Cost-effectiveness analysis of sacral neuromodulation and botulinum toxin A treatment for patients with idiopathic overactive bladder. BJU Int. 2011;108(4):558–64.PubMedCrossRefGoogle Scholar
  31. 31.
    Arlandis S, Castro D, Errando C, Fernandez E, Jimenez M, Gonzalez P, et al. Cost-effectiveness of sacral neuromodulation compared to botulinum neurotoxin a or continued medical management in refractory overactive bladder. Value Health. 2011;14(2):219–28.PubMedCrossRefGoogle Scholar
  32. 32.
    Maria G, Brisinda G, Civello IM, Bentivoglio AR, Sganga G, Albanese A. Relief by botulinum toxin of voiding dysfunction due to benign prostatic hyperplasia: results of a randomized, placebo-controlled study. Urology. 2003;62(2):259–64. discussion 64-5.PubMedCrossRefGoogle Scholar
  33. 33.
    Crawford ED, Hirst K, Kusek JW, Donnell RF, Kaplan SA, McVary KT, et al. Effects of 100 and 300 units of onabotulinum toxin A on lower urinary tract symptoms of benign prostatic hyperplasia: a phase II randomized clinical trial. J Urol. 2011;186(3):965–70.PubMedCrossRefGoogle Scholar
  34. 34.
    Arnouk R, Suzuki Bellucci CH, Benatuil Stull R, de Bessa Jr J, Malave CA, Mendes Gomes C. Botulinum neurotoxin type A for the treatment of benign prostatic hyperplasia: randomized study comparing two doses. Sci World J. 2012;2012:463574. doi:10.1100/2012/463574.CrossRefGoogle Scholar
  35. 35.
    de Kort LM, Kok ET, Jonges TN, Rosier PF, Bosch JL. Urodynamic effects of transrectal intraprostatic Ona botulinum toxin A injections for symptomatic benign prostatic hyperplasia. Urology. 2012;80(4):889–93.PubMedCrossRefGoogle Scholar
  36. 36.
    Sacco E, Bientinesi R, Marangi F, Totaro A, D'Addessi A, Racioppi M, et al. Patient-reported outcomes in men with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) treated with intraprostatic OnabotulinumtoxinA: 3-month results of a prospective single-armed cohort study. BJU Int. 2012;110(11 Pt C):E837–44.PubMedCrossRefGoogle Scholar
  37. 37.
    Hamidi Madani A, Enshaei A, Heidarzadeh A, Mokhtari G, Farzan A, Mohiti Asli M, et al. Transurethral intraprostatic Botulinum toxin-A injection: a novel treatment for BPH refractory to current medical therapy in poor surgical candidates. World J Urol. 2013;31(1):235–9.PubMedCrossRefGoogle Scholar
  38. 38.
    • Marberger M, Chartier-Kastler E, Egerdie B, Lee KS, Grosse J, Bugarin D, et al. A randomized double-blind placebo-controlled phase II dose-ranging study of onabotulinumtoxinA in men with benign prostatic hyperplasia. Eur Urol. 2013;63(3):496–503. Largest RCT assessing BTX-A injections vs placebo into the prostate for BPH..PubMedCrossRefGoogle Scholar
  39. 39.
    Silva J, Pinto R, Carvalho T, Botelho F, Silva P, Silva C, et al. Intraprostatic botulinum toxin type A administration: evaluation of the effects on sexual function. BJU Int. 2011;107(12):1950–4.PubMedCrossRefGoogle Scholar
  40. 40.
    van de Merwe JP, Nordling J, Bouchelouche P, Bouchelouche K, Cervigni M, Daha LK, et al. Diagnostic criteria, classification, and nomenclature for painful bladder syndrome/interstitial cystitis: an ESSIC proposal. Eur Urol. 2008;53(1):60–7.PubMedCrossRefGoogle Scholar
  41. 41.
    Giannantoni A, Bini V, Dmochowski R, Hanno P, Nickel JC, Proietti S, et al. Contemporary management of the painful bladder: a systematic review. Eur Urol. 2012;61(1):29–53.PubMedCrossRefGoogle Scholar
  42. 42.
    Gottsch HP, Miller JL, Yang CC, Berger RE. A pilot study of botulinum toxin for interstitial cystitis/painful bladder syndrome. Neurourol Urodyn. 2011;30(1):93–6.PubMedCrossRefGoogle Scholar
  43. 43.
    Chung SD, Kuo YC, Kuo HC. Intravesical onabotulinumtoxinA injections for refractory painful bladder syndrome. Pain Phys. 2012;15(3):197–202.Google Scholar
  44. 44.
    Pinto R, Lopes T, Silva J, Silva C, Dinis P, Cruz F. Persistent therapeutic effect of repeated injections of onabotulinum toxin a in refractory bladder pain syndrome/interstitial cystitis. J Urol. 2013;189(2):548–53.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Uro-NeurologyUCL Institute of Neurology and The National Hospital for Neurology and NeurosurgeryLondonUK
  2. 2.MRC Centre for Transplantation, King’s College London, King’s Health Partners, Department of UrologyGuy’s HospitalLondonUK

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