Treatment of Non-neurogenic Overactive Bladder with OnabotulinumtoxinA: Systematic Review and Meta-analysis of Prospective, Randomized, Placebo-controlled Clinical Trials

Raquel Martins Arruda; Claudia Cristina Takano; Manoel João Batista Castelo Girão; Jorge Milhem Haddad; Gabriel Francisco Aleixo; Rodrigo Aquino Castro

doi:10.1055/s-0038-1642631

Revista Brasileira de Ginecologia e Obstetrícia / RBGO Gynecology and Obstetrics, Table of Contents

CC-BY-NC-ND 4.0 · Rev Bras Ginecol Obstet 2018; 40(04): 225-231
DOI: 10.1055/s-0038-1642631

Review Article

Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil

Treatment of Non-neurogenic Overactive Bladder with OnabotulinumtoxinA: Systematic Review and Meta-analysis of Prospective, Randomized, Placebo-controlled Clinical Trials^[*]

Tratamento da bexiga hiperativa não neurogênica com toxina botulínica A: revisão sistemática e metanálise de ensaios clínicos prospectivos, randomizados e placebo-controlados*

Raquel Martins Arruda

¹Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil

,

Claudia Cristina Takano

¹Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil

,

Manoel João Batista Castelo Girão

¹Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil

,

Jorge Milhem Haddad

²Universidade de São Paulo (USP), São Paulo, SP, Brazil

,

Gabriel Francisco Aleixo

³Universidade do Oeste Paulista, Presidente Prudente, SP, Brazil

,

Rodrigo Aquino Castro

¹Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil

› Author Affiliations

Abstract

We performed a systematic review and meta-analysis of randomized placebo-controlled trials that studied non-neurogenic overactive bladder patients who were treated with 100 units of onabotulinumtoxinA or placebo. The primary purpose of our study was to evaluate the clinical effectiveness with regard to urinary urgency, urinary frequency, nocturia, and incontinence episodes. Our secondary purpose consisted of evaluating the adverse effects. Our initial search yielded 532 entries. Of these, seven studies met all the inclusion criteria (prospective, randomized, placebo-controlled studies, ≥ 3 points on the Jadad scale) and were selected for analysis. For all primary endpoints, the toxin was more effective than placebo (p < 0.0001; 95% confidence interval [95CI]), namely: urgency (mean difference = -2.07; 95CI = [-2.55–1.58]), voiding frequency (mean difference = -1.64; 95CI = [-2.10–1.18]), nocturia (mean difference = -0.25; 95CI = [-0.39–0.11]) and incontinence episodes (mean difference = -2.06; 95CI= [-2.60–1.52]). The need for intermittent catheterization and the occurrence of urinary tract infection (UTI) were more frequent in patients treated with onabotulinumtoxinA than in patients treated with placebo (p < 0.0001). Compared with placebo, onabotulinumtoxinA had significantly and clinically relevant reductions in overactive bladder symptoms and is associated with higher incidence of intermittent catheterization and UTI.

Resumo

Realizou-se revisão sistemática e metanálise de estudos clínicos prospectivos, randomizados e placebo-controlados que comparavam a toxina botulínica ao placebo no tratamento da bexiga hiperativa. O objetivo primário desta metanálise foi avaliar a eficácia da toxina botulínica em relação à urgência urinária, frequência miccional, noctúria e episódios de incontinência. O objetivo secundário foi avaliar os efeitos adversos. Selecionamos estudos que incluíram somente pacientes com bexiga hiperativa não-neurogênica tratada com 100 unidades de onabotulinum toxina A ou placebo (grupo controle). Foram encontrados 532 estudos após as buscas iniciais, dos quais sete apresentaram todos os critérios de inclusão (estudos prospectivos, randomizados, placebo-controlados, ≥ 3 pontos na escala de Jadad) e fizeram parte desta análise. Para todos os objetivos primários a toxina foi mais eficaz do que o placebo, com p < 0,0001 e intervalo de confiança (IC) de 95%: urgência (diferença média = -2,07, IC = [-2,55; -1,58]), freqüência miccional (diferença média = -1,64, IC = [-2,10; -1,18]), noctúria (diferença média = -0,25, IC = [-0,39; -0,11]) e episódios de incontinência (diferença média = -2,06, IC= [-2,60; -1,52]). A necessidade de cateterização intermitente e a ocorrência de infecção urinária (ITU) foram mais frequentes no grupo toxina na comparação com o grupo placebo (p < 0,0001). A toxina botulínica promoveu melhora significativa dos sintomas de bexiga hiperativa na comparação com o placebo. Entretanto, está associada a uma maior incidência de cateterismo intermitente e infecção do trato urinário.

Keywords

overactive bladder - systematic review - botulinum toxin - randomized controlled trials

Palavras-chave

bexiga hiperativa - revisão sistemática - incontinência urinária - toxina botulínica - estudos randomizados controlados

Full Text

References

References
1 Haylen BT, de Ridder D, Freeman RM. , et al; International Urogynecological Association; International Continence Society. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Neurourol Urodyn 2010; 29 (01) 4-20 . Doi: 10.1002/nau.20798
2 Milsom I, Abrams P, Cardozo L, Roberts RG, Thüroff J, Wein AJ. How widespread are the symptoms of an overactive bladder and how are they managed? A population-based prevalence study. BJU Int 2001; 87 (09) 760-766 . Doi: 10.1046/j.1464-410x.2001.02228.x
3 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 (06) 1306-1314 , discussion 1314–1315. Doi: 10.1016/j.eururo.2006.09.019
4 Coyne KS, Wein A, Nicholson S, Kvasz M, Chen CI, Milsom I. Comorbidities and personal burden of urgency urinary incontinence: a systematic review. Int J Clin Pract 2013; 67 (10) 1015-1033 . Doi: 10.1111/ijcp.12164
5 Onukwugha E, Zuckerman IH, McNally D, Coyne KS, Vats V, Mullins CD. The total economic burden of overactive bladder in the United States: a disease-specific approach. Am J Manag Care 2009; 15 (4, Suppl) S90-S97
6 Willis-Gray MG, Dieter AA, Geller EJ. Evaluation and management of overactive bladder: strategies for optimizing care. Res Rep Urol 2016; 8: 113-122 . Doi: 10.2147/RRU.S93636
7 Gormley EA, Lightner DJ, Faraday M, Vasavada SP. ; American Urological Association; Society of Urodynamics, Female Pelvic Medicine. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline amendment. J Urol 2015; 193 (05) 1572-1580 . Doi: 10.1016/j.juro.2015.01.087
8 Lucas MG, Bosch RJ, Burkhard FC. , et al; European Association of Urology. EAU guidelines on surgical treatment of urinary incontinence. Eur Urol 2012; 62 (06) 1118-1129 . Doi: 10.1016/j.eururo.2012.09.023
9 Jadad AR, Moore RA, Carroll D. , et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Control Clin Trials 1996; 17 (01) 1-12 . Doi: 10.1016/0197-2456(95)00134-4
10 Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327 (7414): 557-560 . Doi: 10.1136/bmj.327.7414.557
11 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 (02) 249-256 . Doi: 10.1016/j.eururo.2013.04.001
12 Denys P, Le Normand L, Ghout I. , et al; VESITOX study group in France. Efficacy and safety of low doses of onabotulinumtoxinA for the treatment of refractory idiopathic overactive bladder: a multicentre, double-blind, randomised, placebo-controlled dose-ranging study. Eur Urol 2012; 61 (03) 520-529 . Doi: 10.1016/j.eururo.2011.10.028
13 Dmochowski R, Chapple C, Nitti VW. , et al. Efficacy and safety of onabotulinumtoxinA for idiopathic overactive bladder: a double-blind, placebo controlled, randomized, dose ranging trial. J Urol 2010; 184 (06) 2416-2422 . Doi: 10.1016/j.juro.2010.08.021
14 Dowson C, Sahai A, Watkins J, Dasgupta P, Khan MS. The safety and efficacy of botulinum toxin-A in the management of bladder oversensitivity: a randomised double-blind placebo-controlled trial. Int J Clin Pract 2011; 65 (06) 698-704 . Doi: 10.1111/j.1742-1241.2011.02663.x
15 Flynn MK, Amundsen CL, Perevich M, Liu F, Webster GD. Outcome of a randomized, double-blind, placebo controlled trial of botulinum A toxin for refractory overactive bladder. J Urol 2009; 181 (06) 2608-2615 . Doi: 10.1016/j.juro.2009.01.117
16 Nitti VW, Dmochowski R, Herschorn S. , et al; EMBARK Study Group. OnabotulinumtoxinA for the treatment of patients with overactive bladder and urinary incontinence: results of a phase 3, randomized, placebo controlled trial. J Urol 2013; 189 (06) 2186-2193 . Doi: 10.1016/j.juro.2012.12.022
17 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 (04) 556-562 . Doi: 10.1002/nau.21021
18 Cui Y, Wang L, Liu L. , et al. Botulinum toxin-A injections for idiopathic overactive bladder: a systematic review and meta-analysis. Urol Int 2013; 91 (04) 429-438 . Doi: 10.1159/000351037
19 Duthie JB, Vincent M, Herbison GP, Wilson DI, Wilson D. Botulinum toxin injections for adults with overactive bladder syndrome. Cochrane Database Syst Rev 2011; (12) CD005493 . Doi: 10.1002/14651858.CD005493.pub3
20 Rechberger T, Miotła P, Skorupski P, Wróbel A, Tomaszewski J. [The quality of life of patients with overactive bladder after local injections of botulinum toxin A--a preliminary report]. Ginekol Pol 2010; 81 (01) 24-30
21 Brubaker L, Richter HE, Visco A. , et al; Pelvic Floor Disorders Network. Refractory idiopathic urge urinary incontinence and botulinum A injection. J Urol 2008; 180 (01) 217-222 . Doi: 10.1016/j.juro.2008.03.028
22 Marinkovic SP, Rovner ES, Moldwin RM, Stanton SL, Gillen LM, Marinkovic CM. The management of overactive bladder syndrome. BMJ 2012; 344: e2365 . Doi: 10.1136/bmj.e2365

Treatment of Non-neurogenic Overactive Bladder with OnabotulinumtoxinA: Systematic Review and Meta-analysis of Prospective, Randomized, Placebo-controlled Clinical Trials[*]

Treatment of Non-neurogenic Overactive Bladder with OnabotulinumtoxinA: Systematic Review and Meta-analysis of Prospective, Randomized, Placebo-controlled Clinical Trials^[*]