Abstract
Purpose
The aim of this study was to overcome the limitation of overlooking the placebo effect in previous studies and to demonstrate the overall treatment efficacy and safety of botulinum toxin type A (BTX-A) compared with placebo.
Methods
We conducted a systematic review and meta-analysis of the published literature in PubMed, Cochrane Library, and Embase reporting on BTX use in lower urinary tract symptoms (LUTS)/benign prostate hyperplasia (BPH). Single-group analysis for the placebo effect and meta-regression analysis for the moderator effect were performed with high-quality RCTs compared with placebo.
Results
A total of three studies were included, with a total sample size of 522 subjects (260 subjects in the experimental group and 262 subjects in the control group). Study duration ranged from 8 to 24 weeks. The pooled overall SMD in the mean change in IPSS for the BTX-A group versus the placebo group was −1.02 (95 % CI −1.97, −0.07). The other outcomes (Q max, prostate volume, and post-voided residual volume) were not statistically different between the two groups. The placebo effect in single-group analysis ranged from 0 to 27.9 % for IPSS, and from −1.1 to 28.7 % for Q max (lowest to highest, respectively).
Conclusions
This evidence-based systematic review and meta-analysis of the BTX-A injection for LUTS/BPH showed no differences in efficacy compared with placebo and also showed no difference in procedure-related adverse events occurred. Thus, the results of this study do not provide evidence of clinical benefits of using the BTX-A injection for LUTS/BPH in real clinical practice.
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Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, Shibuya K, Salomon JA, Abdalla S, Aboyans V, Abraham J, Ackerman I, Aggarwal R, Ahn SY, Ali MK, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Bahalim AN, Barker-Collo S, Barrero LH, Bartels DH, Basanez MG, Baxter A, Bell ML, Benjamin EJ, Bennett D, Bernabe E, Bhalla K, Bhandari B, Bikbov B, Bin Abdulhak A, Birbeck G, Black JA, Blencowe H, Blore JD, Blyth F, Bolliger I, Bonaventure A, Boufous S, Bourne R, Boussinesq M, Braithwaite T, Brayne C, Bridgett L, Brooker S, Brooks P, Brugha TS, Bryan-Hancock C, Bucello C, Buchbinder R, Buckle G, Budke CM, Burch M, Burney P, Burstein R, Calabria B, Campbell B, Canter CE, Carabin H, Carapetis J, Carmona L, Cella C, Charlson F, Chen H, Cheng AT, Chou D, Chugh SS, Coffeng LE, Colan SD, Colquhoun S, Colson KE, Condon J, Connor MD, Cooper LT, Corriere M, Cortinovis M, de Vaccaro KC, Couser W, Cowie BC, Criqui MH, Cross M, Dabhadkar KC, Dahiya M, Dahodwala N, Damsere-Derry J, Danaei G, Davis A, De Leo D, Degenhardt L, Dellavalle R, Delossantos A, Denenberg J, Derrett S, Des Jarlais DC, Dharmaratne SD, Dherani M, Diaz-Torne C, Dolk H, Dorsey ER, Driscoll T, Duber H, Ebel B, Edmond K, Elbaz A, Ali SE, Erskine H, Erwin PJ, Espindola P, Ewoigbokhan SE, Farzadfar F, Feigin V, Felson DT, Ferrari A, Ferri CP, Fevre EM, Finucane MM, Flaxman S, Flood L, Foreman K, Forouzanfar MH, Fowkes FG, Franklin R, Fransen M, Freeman MK, Gabbe BJ, Gabriel SE, Gakidou E, Ganatra HA, Garcia B, Gaspari F, Gillum RF, Gmel G, Gosselin R, Grainger R, Groeger J, Guillemin F, Gunnell D, Gupta R, Haagsma J, Hagan H, Halasa YA, Hall W, Haring D, Haro JM, Harrison JE, Havmoeller R, Hay RJ, Higashi H, Hill C, Hoen B, Hoffman H, Hotez PJ, Hoy D, Huang JJ, Ibeanusi SE, Jacobsen KH, James SL, Jarvis D, Jasrasaria R, Jayaraman S, Johns N, Jonas JB, Karthikeyan G, Kassebaum N, Kawakami N, Keren A, Khoo JP, King CH, Knowlton LM, Kobusingye O, Koranteng A, Krishnamurthi R, Lalloo R, Laslett LL, Lathlean T, Leasher JL, Lee YY, Leigh J, Lim SS, Limb E, Lin JK, Lipnick M, Lipshultz SE, Liu W, Loane M, Ohno SL, Lyons R, Ma J, Mabweijano J, MacIntyre MF, Malekzadeh R, Mallinger L, Manivannan S, Marcenes W, March L, Margolis DJ, Marks GB, Marks R, Matsumori A, Matzopoulos R, Mayosi BM, McAnulty JH, McDermott MM, McGill N, McGrath J, Medina-Mora ME, Meltzer M, Mensah GA, Merriman TR, Meyer AC, Miglioli V, Miller M, Miller TR, Mitchell PB, Mocumbi AO, Moffitt TE, Mokdad AA, Monasta L, Montico M, Moradi-Lakeh M, Moran A, Morawska L, Mori R, Murdoch ME, Mwaniki MK, Naidoo K, Nair MN, Naldi L, Narayan KM, Nelson PK, Nelson RG, Nevitt MC, Newton CR, Nolte S, Norman P, Norman R, O’Donnell M, O’Hanlon S, Olives C, Omer SB, Ortblad K, Osborne R, Ozgediz D, Page A, Pahari B, Pandian JD, Rivero AP, Patten SB, Pearce N, Padilla RP, Perez-Ruiz F, Perico N, Pesudovs K, Phillips D, Phillips MR, Pierce K, Pion S, Polanczyk GV, Polinder S, Pope CA 3rd, Popova S, Porrini E, Pourmalek F, Prince M, Pullan RL, Ramaiah KD, Ranganathan D, Razavi H, Regan M, Rehm JT, Rein DB, Remuzzi G, Richardson K, Rivara FP, Roberts T, Robinson C, De Leon FR, Ronfani L, Room R, Rosenfeld LC, Rushton L, Sacco RL, Saha S, Sampson U, Sanchez-Riera L, Sanman E, Schwebel DC, Scott JG, Segui-Gomez M, Shahraz S, Shepard DS, Shin H, Shivakoti R, Singh D, Singh GM, Singh JA, Singleton J, Sleet DA, Sliwa K, Smith E, Smith JL, Stapelberg NJ, Steer A, Steiner T, Stolk WA, Stovner LJ, Sudfeld C, Syed S, Tamburlini G, Tavakkoli M, Taylor HR, Taylor JA, Taylor WJ, Thomas B, Thomson WM, Thurston GD, Tleyjeh IM, Tonelli M, Towbin JA, Truelsen T, Tsilimbaris MK, Ubeda C, Undurraga EA, van der Werf MJ, van Os J, Vavilala MS, Venketasubramanian N, Wang M, Wang W, Watt K, Weatherall DJ, Weinstock MA, Weintraub R, Weisskopf MG, Weissman MM, White RA, Whiteford H, Wiersma ST, Wilkinson JD, Williams HC, Williams SR, Witt E, Wolfe F, Woolf AD, Wulf S, Yeh PH, Zaidi AK, Zheng ZJ, Zonies D, Lopez AD, Murray CJ, AlMazroa MA, Memish ZA (2012) Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380:2163–2196
Verhamme KM, Dieleman JP, Bleumink GS, van der Lei J, Sturkenboom MC, Artibani W, Begaud B, Berges R, Borkowski A, Chappel CR, Costello A, Dobronski P, Farmer RD, Jimenez Cruz F, Jonas U, MacRae K, Pientka L, Rutten FF, van Schayck CP, Speakman MJ, Sturkenboom MC, Tiellac P, Tubaro A, Vallencien G, Vela Navarrete R, Triumph Pan European Expert P (2002) Incidence and prevalence of lower urinary tract symptoms suggestive of benign prostatic hyperplasia in primary care—the Triumph project. Eur Urol 42:323–328
Oelke M, Bachmann A, Descazeaud A, Emberton M, Gravas S, Michel MC, N’Dow J, Nordling J, de la Rosette JJ, European Association of U (2013) EAU guidelines on the treatment and follow-up of non-neurogenic male lower urinary tract symptoms including benign prostatic obstruction. Eur Urol 64:118–140
McVary KT, Roehrborn CG, Avins AL, Barry MJ, Bruskewitz RC, Donnell RF, Foster HE Jr, Gonzalez CM, Kaplan SA, Penson DF, Ulchaker JC, Wei JT (2011) Update on AUA guideline on the management of benign prostatic hyperplasia. J Urol 185:1793–1803
Chancellor MB, Fowler CJ, Apostolidis A, de Groat WC, Smith CP, Somogyi GT, Aoki KR (2008) Drug Insight: biological effects of botulinum toxin A in the lower urinary tract. Nat Clin Pract Urol 5:319–328
Jankovic J, Brin MF (1991) Therapeutic uses of botulinum toxin. N Engl J Med 324:1186–1194
Gormley EA, Lightner DJ, Faraday M, Vasavada SP, American Urological A, Society of Urodynamics FPM (2015) Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline amendment. J Urol 193:1572–1580
Silva J, Pinto R, Carvalho T, Botelho F, Silva P, Oliveira R, Silva C, Cruz F, Dinis P (2009) Intraprostatic Botulinum Toxin Type A injection in patients with benign prostatic enlargement: duration of the effect of a single treatment. BMC Urol 9:9
Maria G, Brisinda G, Civello IM, Bentivoglio AR, Sganga G, Albanese A (2003) Relief by botulinum toxin of voiding dysfunction due to benign prostatic hyperplasia: results of a randomized, placebo-controlled study. Urology 62:259–264 (discussion 264–255)
Kuo HC (2005) Prostate botulinum A toxin injection—an alternative treatment for benign prostatic obstruction in poor surgical candidates. Urology 65:670–674
Chuang YC, Chiang PH, Yoshimura N, De Miguel F, Chancellor MB (2006) Sustained beneficial effects of intraprostatic botulinum toxin type A on lower urinary tract symptoms and quality of life in men with benign prostatic hyperplasia. BJU Int 98:1033–1037 (discussion 1337)
Chuang YC, Chiang PH, Huang CC, Yoshimura N, Chancellor MB (2005) Botulinum toxin type A improves benign prostatic hyperplasia symptoms in patients with small prostates. Urology 66:775–779
Brisinda G, Cadeddu F, Vanella S, Mazzeo P, Marniga G, Maria G (2009) Relief by botulinum toxin of lower urinary tract symptoms owing to benign prostatic hyperplasia: early and long-term results. Urology 73:90–94
McVary KT, Roehrborn CG, Chartier-Kastler E, Efros M, Bugarin D, Chen R, Patel A, Haag-Molkenteller C (2014) A multicenter, randomized, double-blind, placebo controlled study of onabotulinumtoxinA 200 U to treat lower urinary tract symptoms in men with benign prostatic hyperplasia. J Urol 192:150–156
Marberger M, Chartier-Kastler E, Egerdie B, Lee KS, Grosse J, Bugarin D, Zhou J, Patel A, Haag-Molkenteller C (2013) A randomized double-blind placebo-controlled phase 2 dose-ranging study of onabotulinumtoxinA in men with benign prostatic hyperplasia. Eur Urol 63:496–503
Marchal C, Perez JE, Herrera B, Machuca FJ, Redondo M (2012) The use of botulinum toxin in benign prostatic hyperplasia. Neurourol Urodyn 31:86–92
Mangera A, Apostolidis A, Andersson KE, Dasgupta P, Giannantoni A, Roehrborn C, Novara G, Chapple C (2014) An updated systematic review and statistical comparison of standardised mean outcomes for the use of botulinum toxin in the management of lower urinary tract disorders. Eur Urol 65:981–990
Mangera A, Andersson KE, Apostolidis A, Chapple C, Dasgupta P, Giannantoni A, Gravas S, Madersbacher S (2011) Contemporary management of lower urinary tract disease with botulinum toxin A: a systematic review of botox (onabotulinumtoxinA) and dysport (abobotulinumtoxinA). Eur Urol 60:784–795
Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e1000097
DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188
Chuang YC, Huang CC, Kang HY, Chiang PH, Demiguel F, Yoshimura N, Chancellor MB (2006) Novel action of botulinum toxin on the stromal and epithelial components of the prostate gland. J Urol 175:1158–1163
van Leeuwen JH, Castro R, Busse M, Bemelmans BL (2006) The placebo effect in the pharmacologic treatment of patients with lower urinary tract symptoms. Eur Urol 50:440–452 (discussion 453)
Kallmes DF, Comstock BA, Heagerty PJ, Turner JA, Wilson DJ, Diamond TH, Edwards R, Gray LA, Stout L, Owen S, Hollingworth W, Ghdoke B, Annesley-Williams DJ, Ralston SH, Jarvik JG (2009) A randomized trial of vertebroplasty for osteoporotic spinal fractures. N Engl J Med 361:569–579
Pickard R (2008) Editorial comment on: intraprostatic and bladder-neck injection of botulinum A toxin in treatment of males with bladder-neck dyssynergia: a pilot study. Eur Urol 53:626
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This work was supported by Soonchunhyang University Research Fund.
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Shim, S.R., Cho, Y.J., Shin, IS. et al. Efficacy and safety of botulinum toxin injection for benign prostatic hyperplasia: a systematic review and meta-analysis. Int Urol Nephrol 48, 19–30 (2016). https://doi.org/10.1007/s11255-015-1153-3
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DOI: https://doi.org/10.1007/s11255-015-1153-3