ABSTRACT

Objective

To prospectively compare the results of intradetrusor onabotulinumtoxinA injections and oral oxybutynin for urinary continence, urodynamic parameters and quality of life in patients with neurogenic detrusor overactivity due to spinal cord injury.

Methods

Adult patients under intermittent catheterization were randomized 1:1 to receive one injection of onabotulinumtoxinA 300U or oxybutynin 5mg, per oris, three times/day. Primary study endpoint was change in urinary incontinence episodes/24 hours and secondary study endpoints were maximum cystometric capacity, maximum detrusor pressure, bladder compliance and quality of life before randomization and at week 24.

Results

Sixty-eight patients participated in the trial. Significant improvements in urinary incontinence per 24 hours, all investigated urodynamic parameters and quality of life were observed in both groups. Compared with oral oxybutynin, onabotulinumtoxinA was significantly more efficacious for all parameters investigated. Non-response to treatment was higher for oral oxybutynin (23.5%) than onabotulinumtoxinA (11.8%). Dry mouth was the most common adverse in patients with oral oxybutynin (72%) and transient macroscopic hematuria in patients with onabotulinumtoxinA (28%). Only one patient with oral oxybutynin dropped out the study because of adverse effects.

Conclusion

The comparison of the two study drugs showed that onabotulinumtoxinA was significantly more efficacious than oral oxybutynin with regard to continence, urodynamic parameters and quality of life. Clinicaltrials.gov: NCT:01477736.

Mandelic acids; Botulinum toxins, type A; Urinary bladder, neurogenic; Spinal cord injury; Urodynamics; Quality of life

RESUMO

Objetivo

Comparar prospectivamente os resultados de injeções intradetrusoras de onabotulinumtoxinA e oxibutinina oral em pacientes com hiperatividade neurogênica do detrusor devido à lesão da medula espinhal, para avaliar a continência urinária, os parâmetros urodinâmicos e a qualidade de vida.

Métodos

Pacientes adultos em cateterismo intermitente foram randomizados 1:1 para tratamento com uma injeção de onabotulinumtoxinA 300U ou oxibutinina 5mg via oral, três vezes por dia. O desfecho primário foi alteração nos episódios de incontinência urinária em 24 horas, e os secundários foram capacidade cistométrica máxima, pressão máxima do detrusor, complacência vesical e qualidade de vida antes da randomização e na 24ª semana.

Resultados

Participaram do estudo 68 pacientes. Observou-se melhora significativa na incontinência urinária por 24 horas em todos os parâmetros urodinâmicos investigados e na qualidade de vida em ambos os grupos. Em comparação com a oxibutinina oral, a onabotulinumtoxinA foi significativamente mais eficaz para todos os parâmetros investigados. A falha no tratamento foi maior para oxibutinina oral (23,5%) em comparação com onabotulinumtoxinA (11,8%). A boca seca foi o evento adverso mais comum em pacientes tratados com oxibutinina oral (72%), e a hematúria macroscópica transitória naqueles tratados com onabotulinumtoxinA (28%). Apenas um paciente tratado com oxibutinina oral interrompeu o estudo por conta dos efeitos adversos.

Conclusão

A comparação dos dois fármacos do estudo mostrou que onabotulinumtoxinA foi significativamente mais eficaz que oxibutinina oral em relação a continência, parâmetros urodinâmicos e qualidade de vida. Clinicaltrials.gov: NCT:01477736.

Ácidos mandélicos; Toxinas botulínicas Tipo A; Bexiga urinária neurogênica; Traumatismos da medula espinal; Urodinâmica; Qualidade de vida

INTRODUCTION

Spinal cord injury (SCI) is associated with neurogenic bladder dysfunction and neurogenic detrusor overactivity (NDO). The primary treatment goal is preservation of renal function.⁽¹1. Pannek J, Göcking K, Bersch U. Long-term effects of repeated intradetrusor botulinum neurotoxin A injections on detrusor function in patients with neurogenic bladder dysfunction. BJU Int. 2009;104(9):1246-50.⁾ Patients with neurogenic bladder dysfunction frequently complain about urinary incontinence that may severely affect quality of life.⁽²2. Grise P, Ruffion A, Denys P, Egon G, Chartier Kastler E. Efficacy and tolerability of botulinum toxin type A in patients with neurogenic detrusor overactivity and without concomitant anticholinergic therapy: comparison of two doses. Eur Urol. 2010;58(5):759-66.⁾

Oral antimuscarinics, such as oxybutynin (Oxy), are widely used as first-line treatment of NDO. However, Oxy or other antimuscarinics may be inefficacious in some patients and cause adverse events, such as dry mouth, constipation or blurred vision.⁽³3. Karsenty G, Denys P, Amarenco G, De Seze M, Gamé X, Haab F, et al. Botulinum toxin A (Botox) intradetrusor injections in adults with neurogenic detrusor overactivity/neurogenic overactive bladder: a systematic literature review. Eur Urol. 2008;53(2):275-87. Review.⁾

Intradetrusor injections of onabotulinumtoxinA (OnabotA) have been used as a second-line treatment for patients who do not tolerate or inadequately respond to antimuscarinic agents.⁽⁴4. Abdel-Meguid TA. Botulinum toxin-A injections into neurogenic overactive bladder--to include or exclude the trigone? A prospective, randomized, controlled trial. J Urol. 2010;184(6):2423-8.⁾ The effects of OnabotA on the neuromuscular junction have been extensively investigated and consist of inhibition of acetylcholine release and muscle relaxation.⁽⁵5. Schurch B, de Sèze M, Denys P, Chartier-Kastler E, Haab F, Everaert K, Plante P, Perrouin-Verbe B, Kumar C, Fraczek S, Brin MF; Botox Detrusor Hyperreflexia Study Team. Botulinum toxin type a is a safe and effective treatment for neurogenic urinary incontinence: results of a single treatment, randomized, placebo controlled 6-month study. J Urol. 2005;174(1):196-200.⁾ OnabotA also inhibits other neurotransmitters (e.g. adenosine triphosphate) or neuropeptides (e.g. substance P),⁽⁶6. Apostolidis A, Haferkamp A, Aoki KR. Understanding the role of botulinum toxin A in the treatment of the overactive bladder - more than just muscle relaxation. Eur Assoc Urol. 2006;5(1):670-8.⁾ and regulates the expression of purinergic receptors and transient receptor potential vanilloid receptor-1 (TRVP1) in afferent bladder wall neurons.⁽⁷7. Apostolidis A, Popat R, Yiangou Y, Cockayne D, Ford AP, Davis JB, et al. Decreased sensory receptors P2X3 and TRPV1 in suburothelial nerve fibers following intradetrusor injections of botulinum toxin for human detrusor overactivity. J Urol. 2005;174(3):977-82; discussion 982-3.⁾ Intradetrusor OnabotA therapy for NDO improves urodynamic parameters, such as maximum cystometric capacity (MCC), maximum detrusor pressure (Pdet_max) and bladder compliance, in addition to quality of life.⁽⁵5. Schurch B, de Sèze M, Denys P, Chartier-Kastler E, Haab F, Everaert K, Plante P, Perrouin-Verbe B, Kumar C, Fraczek S, Brin MF; Botox Detrusor Hyperreflexia Study Team. Botulinum toxin type a is a safe and effective treatment for neurogenic urinary incontinence: results of a single treatment, randomized, placebo controlled 6-month study. J Urol. 2005;174(1):196-200.^,88. Schurch B, Stöhrer M, Kramer G, Schmid DM, Gaul G, Hauri D. 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):692-7.⁾ Wu et al.,⁽⁹9. Wu JM, Siddiqui NY, Amundsen CL, Myers ER, Havrilesky LJ, Visco AG. Cost-effectiveness of botulinum toxin A versus anticholinergic medications for idiopathic urge incontinence. J Urol. 2009;181(5):2181-6.⁾ reported the cost-benefit ratio of OnabotA treatment is superior to that of antimuscarinics for NDO. OnabotA has also shown to significantly reduce drug costs associated with urinary tract infections.⁽¹⁰10. Wefer B, Ehlken B, Bremer J, Burgdörfer H, Domurath B, Hampel C, et al. Treatment outcomes and resource use of patients with neurogenic detrusor overactivity receiving botulinum toxin A (BOTOX) therapy in Germany. World J Urol. 2010;28(3):385-90.⁾

To date, no randomized trial has ever compared oral antimuscarinics with intradetrusor OnabotA injections for treating NDO.

OBJECTIVE

To prospectively compare the results of oral oxybutynin and intradetrusor onabotulinumtoxinA injections in patients with neurogenic detrusor overacitvity.

METHODS

Study design and patient selection

This prospective, randomized and controlled clinical trial was performed in adult patients with SCI and NDO in two centers. The study was initiated in 2010 after approval by the Ethics Committee of the Faculdade de Ciências Médicas da Universidade Estadual de Campinas, under number 118/2010, CAAE: 0098.0.146.000-10, and endorsement by the Board of the Centro de Reabilitação e Readaptação Dr. Henrique Santillo (CRER). Each patient read and signed the informed consent before enrollment.

Patients were randomized 1:1 by using sealed, opaque, sequentially numbered envelopes and, afterwards, received immediate-release oral Oxy 5mg three-times/day, or one intradetrusor injection of 300U OnabotA. The primary endpoint was to determine the number of incontinence episodes in 24 hours, in a 3-day bladder diary; and the secondary endpoint was to evaluate changes in urodynamic parameters (MCC, Pdet_max, and bladder compliance) as well as in quality of life, as measured by the Qualiveen questionnaire, between baseline and week 24.

The main inclusion criteria were age >18 years, SCI for at least 12 months, and regular clean intermittent catheterization. Exclusion criteria included pregnancy, a desire to become pregnant during the study period, breastfeeding, use of anticoagulants or known coagulation disorders, neuromuscular transmission disorder, use of any intravesical drug, or previous use of OnabotA. All patients discontinued oral antimuscarinics 7 days before baseline evaluation, and received antibiotics before treatment. Urinary continence was defined as the absence of urinary incontinence in the intervals between catheterizations.⁽¹1. Pannek J, Göcking K, Bersch U. Long-term effects of repeated intradetrusor botulinum neurotoxin A injections on detrusor function in patients with neurogenic bladder dysfunction. BJU Int. 2009;104(9):1246-50.⁾

All patients were first clinically evaluated according to the neurologic scale developed by the American Spinal Injury Association (ASIA).⁽¹¹11. Maynard FM Jr, Bracken MB, Creasey G, Ditunno JF Jr., Donovan WH, Ducker TB, et al. International Standards for Neurological and Functional Classification of Spinal Cord Injury. American Spinal Injury Association. Spinal Cord. 1997; 35(5):266-74.⁾ Laboratory tests included blood urea nitrogen and serum creatinine concentrations, urinalysis and, if indicated, urine culture and imaging. Patients were asked to keep a 3-day bladder diary, documenting frequency, hours and incontinence episodes between catheterizations. All patients also completed the Qualiveen questionnaire, which is a disease-specific tool developed to evaluate the general and urinary-related impact on quality of life in SCI patients. The validated questionnaire underwent successful cross-cultural adaptation into English and was later translated into Portuguese.⁽¹²12. D’Ancona CA, Tamanini JT, Botega N, Lavoura N, Ferreira R, Leitao V, et al. Quality of life of neurogenic patients: translation and validation of the Portuguese version of Qualiveen. Int Urol Nephrol. 2009;41(1):29-33.⁾ Urodynamic studies were carried out according to the recommendations of the International Continence Society (ICS).⁽¹³13. Schäfer W, Abrams P, Liao L, Mattiasson A, Pesce F, Spangberg A, Sterling AM, Zinner NR, van Kerrebroeck P; International Continence Society. Good urodynamic practices: uroflowmetry, filling cystometry, and pressure-flow studies. Neurourol Urodyn. 2002;21(3):261-74.^,1414. Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, Van Kerrebroeck P, Victor A, Wein A; Standardisation Sub-Committee of the International Continence Society. The standardisation of terminology in lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Urology. 2003;61(1):37-49. Review.⁾

Patient treatment and follow-up

Intradetrusor injections were performed on the third day of antibiotic course in a surgical setting, when patients were sedated with 2mg/kg of intravenous propofol. Three hundred units of OnabotA (Botox^®, Allergan, São Paulo, SP, Brazil) were injected into the detrusor with low bladder filling, as described by Schurch et al.⁽⁸8. Schurch B, Stöhrer M, Kramer G, Schmid DM, Gaul G, Hauri D. 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):692-7.⁾ The dose of 300U was chosen because at the time of recruitment this dose was the most frequently used and recommended for the treatment of NDO.

The bladder diary, urodynamic testing with determination of baseline urodynamic parameters, and quality of life evaluation were performed before randomization, repeated at week 4 and at the end of follow-up period at week 24. Patients were asked to report about any adverse event during the follow-up visits. Treatment non-response was defined when urodynamic parameters did not improve and urinary incontinence was not reduced. Non-responders were offered OnabotA injection therapy after 12 weeks (OnabotA Group) or 24 weeks (Oxy Group).

Statistical analysis

The study was planned to accept an error of 5% and a power of 80%. The sample size was determined by using the effect size of urodynamic parameters (primary efficacy parameters) of previous studies while the quality of life scores were determined as secondary efficacy parameter. The χ² test and Fisher’s exact test were used to compare categorical variables between the two groups. For comparison of baseline parameters of the two treatment groups, continuous variables were analyzed by the Mann-Whitney U test since groups and parameters were not normally distributed. The Wilcoxon test was applied to compare any intragroup variations in numeric variables between the baseline evaluations and study end. The significance level for the statistical tests was 5%. SAS version 9.1.3 (SAS Institute, USA) was employed for all statistical analyses.

RESULTS

A total of 73 patients accepted to participate in this study; however, 5 were excluded for not fulfilling the inclusion criteria or drop out. Therefore, 68 patients participated in the study and were randomly selected to receive Oxy or OnabotA (Figure 1). Seven patients (10.3%) prematurely discontinued the study. Of 61 remaining patients who completed the study, 49 (80.3%) were male. The demographic and baseline data of patients who completed the study are summarized in table 1. No statistically significant differences were found between the two groups.

Efficacy parameters

Both Oxy and OnabotA treatments resulted in significant improvement in number of incontinence episodes in 24 hours (Table 2). Maximum cystometric capacity and bladder compliance significantly increased, while Pdet_max decreased. Both treatments promoted a significant impact on quality of life. There were less adverse effects with OnabotA than with oxy.

Non-responders and second-line therapies

Eight patients (23.5%) of the Oxy Group and four (11.8%) of the OnabotA Group did not respond to the treatment. Oxy non-responders received 300U OnabotA injections and all showed a good response. OnabotA non-responders were treated with a second OnabotA injection of 300U after which two patients (50%) presented a good response. Two non-responding patients (50%) underwent enterocystoplasty.

Adverse effects

Macroscopic hematuria was present during the first 24 hours in eight (28%) OnabotA patients. Dry mouth was the most commonly reported adverse event in the Oxy Group (72%), but only one (2.9%) patient discontinued the study for this reason. Eight (23.5%) patients reported a worsening of constipation. No systemic adverse events with OnabotA were reported.

DISCUSSION

This is the first study to have randomized NDO patients who were treated either with oral Oxy or OnabotA injections. The study fulfilled all quality criteria of a randomized, controlled trial and was adequately powered to compare the groups. Our prospective investigation showed that urodynamic (MCC, Pdet_max and bladder compliance), clinical (incontinence episodes/24h) and quality of life parameters significantly improved from baseline to study end (24 weeks), with both Oxy and OnabotA. However, improvement was significantly greater with intradetrusor OnabotA injections. The responder rate was also higher with OnabotA (88.2%) compared with Oxy (76.5%). Both treatments were safe but the adverse events profile seemed to be in favor of OnabotA. Short-term macroscopic hematuria after intradetrusor OnabotA injections in 28% of patients had to be balanced against long-term dry mouth in 72% and constipation in 23.5% of Oxy patients.

Urodynamic studies, with or without active treatment, in patients with NDO due to SCI are scarce. Stöhrer et al.,⁽¹⁵15. Stöhrer M, Mürtz G, Kramer G, Schnabel F, Arnold EP, Wyndaele JJ; Propiverine Investigator Group. Propiverine compared to oxybutynin in neurogenic detrusor overactivity--results of a randomized, double-blind, multicenter clinical study. Eur Urol. 2007;51(1):235-42.⁾ investigated 131 NDO patients (122 with SCI) who were treated with Oxy 15mg/day over a 3-week period. Similar to the present study, the investigators reported a significant improvement of urinary incontinence, MCC, bladder compliance, Pdet_max, and quality of life. Homma et al.,⁽¹⁶16. Homma Y, Paick JS, Lee JG, Kawabe K; Japanese and Korean Tolterodine Study Group. Clinical efficacy and tolerability of extended-release tolterodine and immediate-release oxybutynin in Japanese and Korean patients with an overactive bladder: a randomized, placebo-controlled trial. BJU Int. 2003; 92(7):741-7. Erratum in: BJU Int. 2004;93(7):1135.⁾ reported that, although tolterodine had a lower rate of adverse events, Oxy was superior to placebo in improving quality of life. In the present study, 2.9% of patients treated with Oxy were unable to tolerate dry mouth. Yarker et al.,⁽¹⁷17. Yarker YE, Goa KL, Fitton A. Oxybutynin. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic use in detrusor instability. Drugs Aging. 1995;6(3):243-62. Review.⁾ reported about a discontinuation rate of 25% caused by adverse events due to orally administered, immediate-release Oxy.

Immediate-release Oxy was chosen as a comparator to OnabotA since several controlled studies showed this drug is effective for the treatment of NDO⁽¹⁸18. Andersson KE, Chapple CR. Oxybutynin and the overactive bladder. World J Urol. 2001;19(5):319-23. Review.⁾ and, additionally, Oxy is the only antimuscarinic drug reimbursed by the Brazilian public healthcare system. Oral Oxy is also the only available drug for this indication in most countries, whereas other antimuscarinics are too expensive or have not been globally approved. On the other hand, intradetrusor OnabotA injections are reimbursed in Brazil as second-line treatment of NDO. The 300U dose of OnabotA was chosen because it was often used to treat NDO at the time of patient recruitment. Patients allocated to the 300U OnabotA Group demonstrated a significant improvement of all evaluated urodynamic parameters; therefore, our results are comparable to those published by Reitz et al.,⁽¹⁹19. Reitz A, Stöhrer M, Kramer G, Del Popolo G, Chartier-Kastler E, Pannek J, et al. European experience of 200 cases treated with botulinum-A toxin injections into the detrusor muscle for urinary incontinence due to neurogenic detrusor overactivity. Eur Urol. 2004;45(4):510-5.⁾ However, Cruz et al.,⁽²⁰20. 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.⁾ and Ginsberg et al.,⁽²¹21. Ginsberg D, Gousse A, Keppenne V, Sievert KD, Thompson C, Lam W, et al. Phase 3 efficacy and tolerability study of onabotulinumtoxinA for urinary incontinence from neurogenic detrusor overactivity. J Urol. 2012;187(6): 2131-9.⁾ lately reported that no clinically relevant benefit exists for the 300U over the 200U dose of OnabotA with regard to efficacy or duration of effects.

We also observed a significant reduction of the number of urinary incontinence episodes per 24 hours in the OnabotA-treated group; thus, we could confirm results of the two largest randomized-controlled trials published.⁽¹⁹19. Reitz A, Stöhrer M, Kramer G, Del Popolo G, Chartier-Kastler E, Pannek J, et al. European experience of 200 cases treated with botulinum-A toxin injections into the detrusor muscle for urinary incontinence due to neurogenic detrusor overactivity. Eur Urol. 2004;45(4):510-5.^,2020. 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.⁾ The OnabotA patients of our study also experienced a significant improvement of quality of life. Schurch et al.,⁽²²22. Schurch B, Denys P, Kozma CM, Reese PR, Slaton T, Barron RL. Botulinum toxin A improves the quality of life of patients with neurogenic urinary incontinence. Eur Urol. 2007;52(3):850-8.⁾ reported an improvement in quality of life in 59 patients who were allocated to three groups and treated with 300U or 200U of OnabotA or placebo, and then followed-up for 24 weeks. This study demonstrated a significant improvement of quality of life scores in patients treated with OnabotA, as compared to placebo.

Comparison of the mean differences between the two groups in urodynamic parameters, from baseline to 24 weeks, demonstrated that OnabotA injection therapy was superior to Oxy with regard to all parameters analyzed. The improved urodynamic parameters resulted in a higher continence rate and, secondarily, in a greater impact on quality of life. According to Pannek et al.,⁽²³23. Pannek J, Kullik B. Does optimizing bladder management equal optimizing quality of life? Correlation between health-related quality of life and urodynamic parameters in patients with spinal cord lesions. Urology. 2009; 74(2):263-6.⁾ treatment regimens resulting in improved urodynamic outcome and urinary continence are associated with quality of life improvement. We believe that in our study another factor contributed to improved quality of life in the OnabotA Group, i.e., the better tolerability profile since no long-term adverse events were reported. Dry mouth was the adverse event most often described by patients treated with Oxy (72%) in our study, compared with 17 to 97% of patients receiving immediate-release oral Oxy in the literature.⁽²⁴24. Abrams P, Andersson KE. Muscarinic receptor antagonists for overactive bladder. BJU Int. 2007;100(5):987-1006. Review.⁾ Mild macroscopic hematuria during the first 24 hours after intradetrusor OnabotA injection was found in eight (28%) patients, in comparison with the incidence rate of 2 to 21% reported by Karsenty et al.,⁽³3. Karsenty G, Denys P, Amarenco G, De Seze M, Gamé X, Haab F, et al. Botulinum toxin A (Botox) intradetrusor injections in adults with neurogenic detrusor overactivity/neurogenic overactive bladder: a systematic literature review. Eur Urol. 2008;53(2):275-87. Review.⁾ Autonomic dysreflexia during urodynamic investigation or bladder filling for OnabotA injections could be a potential threat especially in SCI patients with a complete lesion above T6.⁽²⁵25. Curt A, Nitsche B, Rodic B, Schurch B, Dietz V. Assessment of autonomic dysreflexia in patients with spinal cord injury. J Neurol Neurosurg Psychiatry. 1997;62(5):473-7.⁾

Urinary continence rates in our study were significantly higher in patients with OnabotA (60%) compared with Oxy (6%). Karsenty et al.,⁽³3. Karsenty G, Denys P, Amarenco G, De Seze M, Gamé X, Haab F, et al. Botulinum toxin A (Botox) intradetrusor injections in adults with neurogenic detrusor overactivity/neurogenic overactive bladder: a systematic literature review. Eur Urol. 2008;53(2):275-87. Review.⁾ found urinary continence ranging from 40 to 80%; therefore, our results are in accordance with those previously published. SCI experts agree that achieving continence and decrease in Pdet_max (<40cmH₂O) are two key components of NDO management.

In four patients (14%) treated with OnabotA, no changes were found in the urodynamic parameters or quality of life scores, and one patient presented with a reduction in bladder compliance. Reitz et al.⁽¹⁹19. Reitz A, Stöhrer M, Kramer G, Del Popolo G, Chartier-Kastler E, Pannek J, et al. European experience of 200 cases treated with botulinum-A toxin injections into the detrusor muscle for urinary incontinence due to neurogenic detrusor overactivity. Eur Urol. 2004;45(4):510-5.⁾ identified 9 out of 200 patients (4.5%) who experienced no clinical or urodynamic benefit after OnabotA injections. The reasons for the lack of response in these patients remains unknown, but mistakes made during dilution or intradetrusor injection of OnabotA cannot be excluded.

Although our study had the highest quality standards, there are also limitations. Immediate-release Oxy is associated with the highest rates of adverse events of all antimuscarinics, although dry mouth has also been reported to be the most frequent adverse event with any other antimuscarinic agent. Moreover, immediate-release Oxy is the only oral drug available for the treatment of NDO in the Brazilian public healthcare system and also in many other countries. We compared only two different modalities for the treatment of NDO but future studies need to compare OnabotA injections with other antimuscarinics drugs. Blinding of patients with placebo (in the Oxy Group) or sham treatment (in the OnabotA Group) would have been desirable but was not granted by the local ethic committee to avoid the risk of upper urinary tract damage and guarantee active treatment.

CONCLUSION

The comparison of both objective (bladder diary and urodynamic data) and subjective (quality of life questionnaire) parameters, onabotulinumtoxinA injections were found to be significantly more efficacious than oral oxybutynin. Due to the better results of onabotulinumtoxinA we should consider this treatment as the first line option in neurogenic detrusor overactivity patients when it is only possible to use oxybutynin.

ACKNOWLEDGMENTS

This study was realized by the co-operation and collective efforts of Adriana Soares Adorno, Elcione Lisboa Cardoso, Suely Chaves, Alice Adelaide da Silva, Iris Domenico, Paula Lea F. da Costa Ferreira, Juliana Rampazzo, Edel Maria da Silva e Lima, Thiago Souza Oliveira, Eduardo José de Castro, Rogério Alves Moreira and Reagan Fernandes Rosa.

REFERENCES

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