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Complete Continence after Botulinum Neurotoxin Type A Injections for Refractory Idiopathic Detrusor Overactivity Incontinence: Patient-Reported Outcome at 4 Weeks
EUROPEAN UROLOGY 57 (2010) 891–896
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Incontinence
Complete Continence after Botulinum Neurotoxin Type A Injections for Refractory Idiopathic Detrusor Overactivity Incontinence: Patient-Reported Outcome at 4 Weeks Shahid Khan a, Jalesh Panicker a, Alexander Roosen a,b, Gwen Gonzales a, Sohier Elneil a, Prokar Dasgupta a,c, Clare J. Fowler a,*, Thomas M. Kessler a,d a
Department of Uro-Neurology, National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, UK
b
Department of Urology, Ludwig-Maximilians-University, Munich, Germany
c
Department of Urology, Guys and St. Thomas’ Hospitals NHS Foundation Trust, London, UK
d
Department of Urology, University of Bern, Bern, Switzerland
Article info
Abstract
Article history: Accepted April 8, 2009 Published online ahead of print on April 21, 2009
Background: Objective improvement following intradetrusor injections of botulinum neurotoxin type A (BoNTA) is well documented. Although patient-related outcome measures are highly recommended for monitoring overactive bladder symptoms, no study before has dealt with the question of patient-reported complete continence after BoNTA treatment using validated questionnaires. Objective: To investigate the change in patient-reported continence rate after intradetrusor injections of BoNTA for treatment of refractory idiopathic detrusor overactivity (IDO) incontinence. Design, setting, and participants: Seventy-four patients (51 women, 23 men) with refractory IDO incontinence treated for the first time with intradetrusor injections of 200 U BoNTA were evaluated in this nonrandomised, open-label, cohort study. Measurements: Changes in patient-reported urinary frequency, urgency incontinence, and stress incontinence were assessed using the condition-specific validated short form of the Urogenital Distress Inventory (UDI 6) before and 4 wk after BoNTA treatment. Results and limitations: The patient-reported outcome of complete continence (defined as a score of 0 in both the urgency and stress incontinence subscales of the UDI 6) was 51% (38 of 74) 4 wk after intradetrusor injections of BoNTA. In patients who were not completely continent, median urgency incontinence scores reduced significantly from 100 to 0 ( p < 0.001), stress incontinence scores from 33 to 0 ( p < 0.001), and median urinary frequency scores from 100 to 33 ( p < 0.001), respectively. The inclusion of patients with mixed incontinence may have resulted in underestimation of the complete continence rate. Conclusions: An excellent response with >50% of patients reporting complete continence 4 wk after BoNTA treatment reveals the efficacy of this emerging treatment for patients with refractory IDO incontinence. Furthermore, in those in whom complete continence was not achieved, there was a notable and significant reduction in reported urgency incontinence, stress incontinence, and urinary frequency.
Keywords: Botulinum toxin type A Idiopathic detrusor overactivity incontinence Quality of life Complete continence
# 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.
* Corresponding author. Department of Uro-Neurology, The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK. E-mail address: [email protected] (C.J. Fowler). 0302-2838/$ – see back matter # 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.eururo.2009.04.020
892
1.
EUROPEAN UROLOGY 57 (2010) 891–896
Introduction
pregnancy. No patients with neurogenic detrusor overactivity were included in this study.
Overactive bladder (OAB) is a subgroup of lower urinary tract symptoms (LUTS) defined by the International Continence Society (ICS) as urgency, with or without urgency incontinence (UUI), frequency, and nocturia [1]. The prevalence of OAB symptoms in Europe is reported to be 17.4% in women and 15.6% in men >40 yr, and, overall, 36% had UUI [2]. The National Overactive Bladder Evaluation Programme has reported similar incidence (16% in men and 16.9% in women) in the United States, with 9.3% of women and 2.6% of men having OAB symptoms with UUI. These symptoms had a significant impact on the quality of life, quality of sleep, and mental and social health [3]. The cost of treating clinically significant urinary storage symptoms in the United Kingdom in 2000 was £743 million [4]. It is estimated that the cost of managing OAB in the UK, Italy, Spain, Sweden, and Germany will increase from s4.2 billion in 2000 to s5.2 billion by 2020 [5]. Some 28% of patients presenting with OAB symptoms were prescribed antimuscarinics, 73% of these were referred to secondary specialty care [6], and 25–40% of these patients fail to respond to treatment when urgency incontinence is the primary outcome [3]. Furthermore, 40% of OAB patients discontinue antimuscarinic medications due to adverse events [7]. Intradetrusor injection of botulinum neurotoxin type A (BoNTA) is emerging as the second-line treatment for refractory OAB symptoms secondary to neurogenic detrusor overactivity (NDO) and idiopathic detrusor overactivity (IDO) [8]. As objective measures are poorly representative of or correlated with patient-related outcome measures (PROM), validated subjective instruments are highly recommended for addressing the management of OAB symptoms [9]. Most previous studies have looked at the urodynamic parameters as the primary outcome measures. Werner and colleagues [10] reported ‘‘dry rate’’ based on urodynamics of 54% (14 out of 26) 4 wk after treatment; however, so far, there have been no studies of patient-reported complete continence using validated questionnaires. We, therefore, investigated the patient-reported continence rate after the first intradetrusor injections of BoNTA for treating IDO incontinence.
Urodynamic studies were performed according to the ‘‘good urodynamic practices’’ described by Schafer et al [11]. Urinary tract infections were treated prior to BoNTA injections according to the culture and antibiotic sensitivity report. All patients provided written informed consent before treatment. This study was conducted under a research protocol in the initial 2 yr and had the approval of the local ethics committee. Subsequently, the Trust’s Use of Medicines Committee permitted this off-license treatment for patients with detrusor overactivity. All methods, definitions, and units conform to the standards recommended by the International Continence Society [1].
2.2.
Injection technique
Intradetrusor BoNTA injections were performed in an outpatient setting using the previously described minimally invasive technique [12]. After intraurethral instillation of 20 ml 2% lignocaine gel (Instillagel Farco-Pharma GmbH, Cologne, Germany) and exposure for 2–5 min, a 27G 4-mm long needle (Olympus MAJ-656, KeyMed, Milton Keynes, UK) was passed through the sheath (Olympus NM-101C-0427, KeyMed) of the 2-mm diameter working channel of a flexible cystoscope (Olympus KeyMed) and 200 U of BoNTA (Botox1, Allergan Ltd UK) at 1:10 dilution with 0.9% saline were injected at 20 different sites in the detrusor, sparing the trigone.
2.3.
Patient assessment
Follow-up of bladder diary parameters and urodynamic investigations 4 and 16 wk after BoNTA injections were performed in the early study period (until July 2005) but were not done routinely thereafter since it was apparent the results did not significantly alter the management [13]. Patient-reported continence was assessed using the urgency incontinence and stress incontinence subscales of the Urogenital Distress Inventory (UDI 6) questionnaire (Table 1) [14] before and 4 wk after BoNTA injections. Responses to the UDI 6 subscales—urinary frequency, urgency incontinence, and stress incontinence, which range from 0–3— were transformed to a scale of 0–100 by multiplying by 33.33 according to the recommendation for use of this questionnaire [14]. An outpatient assessment of postvoid residual (PVR) and urine analysis was carried out 2 wk after injections. Written instructions were given to contact the department if bothersome urinary symptoms were a concern. Based on our experience of neurogenic patients’ response to Botox1, we used the criteria for initiating CISC as PVR >100 ml if LUTS persisted. Proven urinary tract infections were treated according to antibiotic sensitivity, but patients were not routinely prescribed prophylactic antibiotics if they were performing CISC. Patients who were on antimuscarinics were advised to reduce or discontinue therapy
2.
Patients and methods
once they noticed improvement in OAB symptoms.
2.1.
Patients
2.4.
Outcome measures
Seventy-four patients with refractory IDO incontinence were treated for
The primary outcome was the patient-reported outcome of complete
the first time once only with intradetrusor injections of 200 U BoNTA in
continence, defined as a score of 0 on both the urgency and stress
this nonrandomised and open-label study between January 2002 and
incontinence subscales of the UDI 6 questionnaire 4 wk after the first
September 2008. The median age of the 74 patients (51 women, 23 men)
BoNTA intradetrusor injection. Secondary outcomes were changes in the
was 56 yr (interquartile range [IQR]: 42–67 yr).
UDI 6 subscales of urinary frequency, urgency incontinence, and stress
Patients with OAB symptoms who were refractory to behavioural
incontinence before and 4 wk after the first injections.
therapy and pharmacotherapy for at least 3 mo were included in the study if standard subtraction filling cystometry revealed detrusor
2.5.
Statistical analysis
overactivity incontinence. Willingness to perform clean intermittent self-catheterisation (CISC) if required after treatment was an important
Data were skewed and are presented as median and IQR. The Wilcoxon
prerequisite. Patients taking anticoagulants or antiplatelets were
signed-rank test was used for comparison of related samples. Unrelated
excluded, as were lactating mothers and women who were planning
samples were compared by applying the Mann-Whitney U test or the
EUROPEAN UROLOGY 57 (2010) 891–896
Table 1 – Items in the Urogenital Distress Inventory Short Form Do you experience, and, if so, how much are you bothered by: 1. Frequent urination 2. Leakage related to feeling of urgency 3. Leakage related to activity, coughing, or sneezing 4. Small amounts of leakage (drops) 5. Difficulty emptying bladder 6. Pain or discomfort in lower abdominal or genital area
chi-square test, as appropriate. A p-value of <0.05 was considered significant. Statistical analysis was performed using SPSS v.16.0 (SPSS Inc, Chicago, IL, USA).
3.
893
urgency incontinence scores were reduced significantly from 100 (IQR: 67–100) to 0 (IQR: 0–33) ( p < 0.001), median stress incontinence scores were reduced significantly from 33 (IQR: 0–67) to 0 (IQR: 0–17) ( p < 0.001), and median urinary frequency scores were reduced significantly from 100 (IQR: 100–100) to 33 (IQR: 0–67) ( p < 0.001), respectively (Fig. 2). Two weeks after BoNTA injections, antibiotic treatment for lower urinary tract infection was required in 11 (15%) of the 74 patients. Prior to BoNTA injections all patients voided spontaneously. Following BoNTA treatment, 29 (39%) of 74 patients required CISC. There was no difference ( p = 0.9) between the reported continence rate in those patients performing CISC (52%; 15 of 29) and those who did not (51%; 23 of 45).
Results 4.
All patients had IDO incontinence. According to the patientreported UDI 6 subscales, 33 (45%) patients reported urgency incontinence and 41 (55%) patients mixed incontinence prior to treatment. Four weeks after BoNTA treatment, the proportion of patients reporting complete restoration of continence was 51% (38 of 74). The continence rate was similar ( p = 0.9) for patients who had reported urgency incontinence (52%; 17 of 33) compared to those who had reported mixed incontinence (51%; 21 of 41). There were 36 patients who were still not completely continent; among these, 19 (53%) reported urgency incontinence, 2 (6%) reported stress incontinence, and 15 (42%) reported mixed incontinence (Fig. 1). Age ( p = 0.6) and gender ( p = 0.3) had no influence on the continence rate after BoNTA treatment. Four weeks after intradetrusor BoNTA injections, there was highly significant ( p < 0.001) improvement in the patient-reported urgency incontinence, stress incontinence, and urinary frequency subscales of the UDI 6. Median
Fig. 1 – Patient-reported incontinence before and 4 wk after intradetrusor injections of botulinum neurotoxin type A (BoNT/A) using the subscales of the validated Urogenital Distress Inventory (UDI 6) questionnaire in 74 patients.
Discussion
It has been reported that between 42–87% patients with NDO incontinence become completely continent between CISC after BoNTA treatment [15]. In this open-labelled study of patients with IDO incontinence treated with intradetrusor BoNTA, 51% reported complete restoration of continence 1 mo after treatment. This is in line with the findings of Werner et al [10], who reported a 54% dry rate after 4 wk, although in that study the evidence was based on urodynamic assessment. Besides this notable improvement, we found a significant reduction in the patient-reported urgency incontinence, stress incontinence, and urinary frequency subscales of the UDI 6 questionnaire. Amelioration in OAB symptoms after BoNTA has been reported previously [16–18], and we found that urgency was the earliest and most consistently affected symptom in a mixed group (IDO and NDO) of patients [19]. The standard first-line pharmacological treatment for OAB symptoms is antimuscarinics, the efficacy of this treatment having been shown in systematic reviews [20,21]. Considering that all our patients were refractory to or could not tolerate the side-effects of antimuscarinic therapy, the fact that >50% became completely continent after intradetrusor BoNTA is impressive as it reflects improvement in the patient cohort with the most severe symptoms. Patients’ perceptions affect treatment expectations, and this, in turn, predicts treatment outcomes [22]. Because physicians underestimate the extent to which patients are affected by their symptoms by 25–37% [23], reports of surgical and medical outcomes after treatment should always include independent, validated questionnaires selfadministered by patients to avoid interviewer bias. Objective measures have correlated poorly with patientrelated outcome measures, suggesting that objective and subjective assessments measure different aspects of the patient profile when comparing the efficacy of antimuscarinic receptor antagonists [24], in contrast to the comparison of our subjective results with those of Werner et al [10]. Flynn et al [25], in their pilot study involving seven female patients, also reported a remarkable improvement in subjective outcome measures but without statistically significant changes in urodynamic parameters using
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EUROPEAN UROLOGY 57 (2010) 891–896
mixed incontinence, which is representative of everyday clinical practice. As this assessment was done before and 1 mo after the first BoNTA treatment, the duration for which complete continence lasts and the effect of repeat injections has not been addressed and will need longer term follow-up. 5.
Conclusions
An excellent response in which >50% of patients reported they are completely continent 4 wk after BoNTA treatment reveals the efficacy of this emerging treatment for patients with refractory IDO incontinence. Furthermore, in those in whom complete continence was not achieved, there was a notable and significant reduction in reported urgency incontinence, stress incontinence, and urinary frequency. Author contributions: Clare Fowler had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Khan, Fowler, Kessler. Acquisition of data: Khan, Roosen. Analysis and interpretation of data: Khan, Kessler. Drafting of the manuscript: Khan, Panicker. Fig. 2 – Decline in patient-reported median Urogenital Distress Inventory subscales of frequency, urgency incontinence, and stress incontinence before versus 4 wk after botulinum neurotoxin type A (BoNT/A) injections.
Critical revision of the manuscript for important intellectual content: Kessler, Panicker, Roosen, Fowler. Statistical analysis: Khan, Kessler. Obtaining funding: None. Administrative, technical, or material support: Gonzales, Dasgupta, Elneil. Supervision: Elneil, Dasgupta, Fowler.
150 U of Botox1, whereas Jeffery et al reported improvement in both subjective and objective parameters using 500 U of Dysport [26]. The short versions of the UDI 6 forms were employed in our department, as they are easy to use in clinical practice and in research to characterise the severity of incontinence [14]. It may be argued that some of the patients reporting stress incontinence after BoNTA treatment could have had overflow incontinence due to a high PVR, and this could influence the reported continence status. However, this seems unlikely as CISC was initiated in those with PVR >100 ml, and, furthermore, the reported complete continence was similar in those performing CISC compared to those who did not. Although >50% of our patients with refractory IDO incontinence treated with intradetrusor injections of 200 U BoNTA reported complete restoration of continence 1 mo after treatment, it remains to be established which dose has the best effect with the lowest CISC rate. The ongoing randomised, placebo-controlled, dose-response study (NCT 00168454) may answer this question and guide the decision on optimum dosage. Mixed urinary incontinence was not an exclusion criterion in the present study. After BoNTA treatment, among the 50% incontinent only two patients reported stress incontinence, implying an even higher dry rate if patients with mixed incontinence were excluded. However, being a nonrandomised study without a placebo arm and involving a subjective outcome assessment that is highly individualised, there could be a bias. The patientreported continence rate in our study reflects a diverse group of patients with urgency incontinence as well as those with
Other (specify): None. Financial disclosures: I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Clare Fowler and Prokar Dasgupta are recipients of unrestricted educational grants from Allergan Ltd and have also acted as consultants for Allergan Ltd. Thomas Kessler is supported by a grant from the Swiss National Science Foundation and has acted as consultant for Medtronic. Alexander Roosen is supported by a grant of the German Research Foundation. Sohier Elneil and Clare Fowler are consultants for Medtronic. Clare Fowler was the recipient of an independent research grant from Pfizer, Inc. Funding/Support and role of the sponsor: Allergan Ltd UK was the gratis provider of Botox1 used in the early period of this study.
References [1] Abrams P, Cardozo L, Fall M, et al. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn 2002;21:167–78. [2] Milsom I, Abrams P, Cardozo L, Roberts RG, Thuroff 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;87:760–6. [3] Stewart WF, Van Rooyen JB, Cundiff GW, et al. Prevalence and burden of overactive bladder in the United States. World J Urol 2003;20:327–36.
EUROPEAN UROLOGY 57 (2010) 891–896
[4] Turner DA, Shaw C, McGrother CW, Dallosso HM, Cooper NJ. The cost of clinically significant urinary storage symptoms for
895
activity/neurogenic overactive bladder: a systematic literature review. Eur Urol 2008;53:275–87.
community dwelling adults in the UK. BJU Int 2004;93:1246–52.
[16] Kalsi V, Apostolidis A, Popat R, Gonzales G, Fowler CJ, Dasgupta
[5] Reeves P, Irwin D, Kelleher C, et al. The current and future burden
P. Quality of life changes in patients with neurogenic versus
and cost of overactive bladder in five European countries. Eur Urol
idiopathic detrusor overactivity after intradetrusor injections of
2006;50:1050–7.
botulinum neurotoxin type A and correlations with lower urin-
[6] Odeyemi IA, Dakin HA, O’Donnell RA, Warner J, Jacobs A, Dasgupta P. Epidemiology, prescribing patterns and resource use associated with overactive bladder in UK primary care. Int J Clin Pract 2006;60:949–58. [7] Kelleher CJ, Cardozo LD, Khullar V, Salvatore S. A medium-term analysis of the subjective efficacy of treatment for women with detrusor instability and low bladder compliance. Br J Obstet Gynaecol 1997;104:988–93. [8] Apostolidis A, Dasgupta P, Denys P, et al. Recommendations on the use of botulinum toxin in the treatment of lower urinary tract disorders and pelvic floor dysfunctions: a European consensus report. Eur Urol 2009;55:100–20. [9] Abrams P, Artibani W, Gajewski JB, Hussain I. Assessment of treatment outcomes in patients with overactive bladder: importance of objective and subjective measures. Urology 2006;68:17–28.
ary tract symptoms and urodynamic changes. Eur Urol 2006; 49:528–35. [17] Sahai A, Khan MS, Dasgupta P. Efficacy of botulinum toxin-A for treating idiopathic detrusor overactivity: results from a single center, randomized, double-blind, placebo controlled trial. J Urol 2007;177:2231–6. [18] Schmid DM, Sauermann P, Werner M, et al. Experience with 100 cases treated with botulinum-A toxin injections in the detrusor muscle for idiopathic overactive bladder syndrome refractory to anticholinergics. J Urol 2006;176:177–85. [19] Kalsi V, Apostolidis A, Gonzales G, Elneil S, Dasgupta P, Fowler CJ. Early effect on the overactive bladder symptoms following botulinum neurotoxin type A injections for detrusor overactivity. Eur Urol 2008;54:181–7. [20] Chapple CR, Khullar V, Gabriel Z, Muston D, Bitoun CE, Weinstein D.
[10] Werner M, Schmid DM, Schussler B. Efficacy of botulinum-A toxin in
The effects of antimuscarinic treatments in overactive bladder: an
the treatment of detrusor overactivity incontinence: a prospective
update of a systematic review and meta-analysis. Eur Urol 2008;
nonrandomized study. Am J Obstet Gynecol 2005;192:1735–40.
54:543–62.
[11] Schafer W, Abrams P, Liao L, et al. Good urodynamic practices:
[21] Novara G, Galfano A, Secco S, et al. A systematic review and meta-
uroflowmetry, filling cystometry, and pressure-flow studies. Neu-
analysis of randomized controlled trials with antimuscarinic drugs
rourol Urodyn 2002;21:261–74.
for overactive bladder. Eur Urol 2008;54:740–64.
[12] Harper M, Popat RB, Dasgupta R, Fowler CJ, Dasgupta P. A minimally
[22] Marschall-Kehrel D, Roberts RG, Brubaker L. Patient-reported out-
invasive technique for outpatient local anaesthetic administration
comes in overactive bladder: the influence of perception of condition
of intradetrusor botulinum toxin in intractable detrusor overactivity. BJU Int 2003;92:325–6. [13] Popat R, Apostolidis A, Kalsi V, Gonzales G, Fowler CJ, Dasgupta P. A comparison between the response of patients with idiopathic detrusor overactivity and neurogenic detrusor overactivity to the first intradetrusor injection of botulinum-A toxin. J Urol 2005;174:984–9.
and expectation for treatment benefit. Urology 2006;68:29–37. [23] Rodriguez LV, Blander DS, Dorey F, Raz S, Zimmern P. Discrepancy in patient and physician perception of patient’s quality of life related to urinary symptoms. Urology 2003;62:49–53. [24] Abrams P, Andersson KE. Muscarinic receptor antagonists for overactive bladder. BJU Int 2007;100:987–1006.
[14] Uebersax JS, Wyman JF, Shumaker SA, McClish DK, Fantl JA. Short
[25] Flynn MK, Webster GD, Amundsen CL. The effect of botulinum-A
forms to assess life quality and symptom distress for urinary
toxin on patients with severe urge urinary incontinence. J Urol
incontinence in women: the Incontinence Impact Questionnaire and the Urogenital Distress Inventory. Continence Program for
2004;172:2316–20. [26] Jeffery S, Fynes M, Lee F, Wang K, Williams L, Morley R. Efficacy and
Women Research Group. Neurourol Urodyn 1995;14:131–9.
complications of intradetrusor injection with botulinum toxin A in
[15] Karsenty G, Denys P, Amarenco G, et al. Botulinum toxin A (Botox1)
patients with refractory idiopathic detrusor overactivity. BJU Int
intradetrusor injections in adults with neurogenic detrusor over-
Editorial Comment on: Complete Continence after Botulinum Neurotoxin Type A Injections for Refractory Idiopathic Detrusor Overactivity Incontinence: Patient-Reported Outcome at 4 Weeks Mehmet Kilinc, Selcuk Guven Department of Urology, Meram Faculty of Medicine, Selcuk University, 42080 Konya, Turkey [email protected] Khan and co-authors investigated the change in patient-reported continence rate after intradetrusor botulinum neurotoxin A (BoNTA) injections for treating idiopathic detrusor overactivity (IDO) incontinence [1]. Assessment of treatment outcomes is a considerable problem of IDO patients. Objective measures of treatment
2007;100:1302–6.
efficacy (eg, urodynamic studies, bladder diary variables) are not always predictive of subjective outcomes, which are influenced by a patient’s priorities and lifestyle [2]. Thus, the patient-reported outcomes are relevant to clinical practice and should be used with objective measures to better evaluate the effects of treatment on IDO patients’ perceptions of health-related quality of life. As there have not yet been any studies on this issue using validated questionnaires, and thus no data are available, the outcome of the present study gains further importance. A number of limitations, however, should be noted. First, the major limitation of this study is a nonrandomised design. Randomised placebo controlled trials are needed to confirm the outcomes mentioned in the study. Second,
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the authors also included the mixed-incontinence patients in the study. The pathophysiological interactions and the clinical evaluation of mixed incontinence are different; thus, although the outcome measures rely on subjective patient-reported questionnaires, stress and urge incontinence should be described separately rather than as a single dimension [3]. Although treatment of IDO patients with BoNTA injections has gained increasing acceptance as a secondline option in management of IDO incontinence, several mysteries remain regarding:
Further large randomised placebo-controlled trials are needed to elucidate the ideal conditions of the BoNTA injections for the IDO patients.
References [1] Khan S, Panicker J, Roosen A, et al. Complete continence after botulinum neurotoxin type A injections for refractory idiopathic detrusor overactivity incontinence: patient reported outcome at 4 weeks. Eur Urol 2010;57:891–6. [2] Abrams P, Artibani W, Gajewski JB, Hussain I. Assessment of treatment outcomes in patients with overactive bladder: importance of
Injection technique, injection site, and number Optimal dose, dosing interval, and best minimal dosage to avoid voiding difficulty Long-term follow-up, duration of continence effect, and the effect of repeat injections Post-treatment follow-up, the number and timing of postresidual voiding assessments, and threshold to begin clean intermittent self-catheterisations.
Editorial Comment on: Complete Continence after Botulinum Neurotoxin Type A Injections for Refractory Idiopathic Detrusor Overactivity Incontinence: Patient-Reported Outcome at 4 Weeks Antonella Giannantoni Department of Urology and Andrology, University of Perugia, Policlinico Monteluce, Perugia, Italy [email protected] In the present article, Khan and co-authors investigated the patient-reported continence rate after the first intradetrusorial injection of botulinum A toxin (BoNTA) in the treatment of idiopathic detrusor overactivity (IDO) [1]. They found that intradetrusorially injected BoNTA not only improved frequency of micturition and urinary urgency but also eliminated urge incontinence in >50% of patients at 4 wk after treatment. As a complication, 39% of these patients required clean intermittent self-catheterization (CISC) to empty their bladders completely after treatment. The main contribution of the present article relies on the use, for the first time, of a validated questionnaire in evaluating the response of IDO patients to BoNTA treatment. Only self-administered validated questionnaires can exactly evaluate the extent to which patients
objective and subjective measures. Urology 2006;68(Suppl):17–28. [3] Brubaker L, Stoddard A, Richter H, et al. Mixed incontinence: comparing definitions in women having stress incontinence surgery. Neurourol Urodyn 2009;28:268–73.
DOI: 10.1016/j.eururo.2009.04.021 DOI of original article: 10.1016/j.eururo.2009.04.020
are affected by their symptoms and whether those symptoms are alleviated by a particular treatment. The major result consists of the fact that all of the patients in the study were refractory to or could not tolerate the side effects of anticholinergic treatment. Thus, the high continence rate is really impressive, as it was obtained in subjects with more severe symptoms. Nevertheless, a question still remains about which dose of BoNTA has the main effect with the lowest CISC rate. This issue is important for future research in this field of application. In all of these respects, the present article represents an important contribution to the growing literature regarding the use of BoNTA in functional urology.
References [1] Khan S, Panicker J, Roosen A, et al. Complete continence after botulinum neurotoxin type A injections for refractory idiopathic detrusor overactivity incontinence: patient-reported outcome at 4 weeks. Eur Urol 2010;57:891–6.
DOI: 10.1016/j.eururo.2009.04.022 DOI of original article: 10.1016/j.eururo.2009.04.020
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Incontinence
Complete Continence after Botulinum Neurotoxin Type A Injections for Refractory Idiopathic Detrusor Overactivity Incontinence: Patient-Reported Outcome at 4 Weeks Shahid Khan a, Jalesh Panicker a, Alexander Roosen a,b, Gwen Gonzales a, Sohier Elneil a, Prokar Dasgupta a,c, Clare J. Fowler a,*, Thomas M. Kessler a,d a
Department of Uro-Neurology, National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, UK
b
Department of Urology, Ludwig-Maximilians-University, Munich, Germany
c
Department of Urology, Guys and St. Thomas’ Hospitals NHS Foundation Trust, London, UK
d
Department of Urology, University of Bern, Bern, Switzerland
Article info
Abstract
Article history: Accepted April 8, 2009 Published online ahead of print on April 21, 2009
Background: Objective improvement following intradetrusor injections of botulinum neurotoxin type A (BoNTA) is well documented. Although patient-related outcome measures are highly recommended for monitoring overactive bladder symptoms, no study before has dealt with the question of patient-reported complete continence after BoNTA treatment using validated questionnaires. Objective: To investigate the change in patient-reported continence rate after intradetrusor injections of BoNTA for treatment of refractory idiopathic detrusor overactivity (IDO) incontinence. Design, setting, and participants: Seventy-four patients (51 women, 23 men) with refractory IDO incontinence treated for the first time with intradetrusor injections of 200 U BoNTA were evaluated in this nonrandomised, open-label, cohort study. Measurements: Changes in patient-reported urinary frequency, urgency incontinence, and stress incontinence were assessed using the condition-specific validated short form of the Urogenital Distress Inventory (UDI 6) before and 4 wk after BoNTA treatment. Results and limitations: The patient-reported outcome of complete continence (defined as a score of 0 in both the urgency and stress incontinence subscales of the UDI 6) was 51% (38 of 74) 4 wk after intradetrusor injections of BoNTA. In patients who were not completely continent, median urgency incontinence scores reduced significantly from 100 to 0 ( p < 0.001), stress incontinence scores from 33 to 0 ( p < 0.001), and median urinary frequency scores from 100 to 33 ( p < 0.001), respectively. The inclusion of patients with mixed incontinence may have resulted in underestimation of the complete continence rate. Conclusions: An excellent response with >50% of patients reporting complete continence 4 wk after BoNTA treatment reveals the efficacy of this emerging treatment for patients with refractory IDO incontinence. Furthermore, in those in whom complete continence was not achieved, there was a notable and significant reduction in reported urgency incontinence, stress incontinence, and urinary frequency.
Keywords: Botulinum toxin type A Idiopathic detrusor overactivity incontinence Quality of life Complete continence
# 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.
* Corresponding author. Department of Uro-Neurology, The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK. E-mail address: [email protected] (C.J. Fowler). 0302-2838/$ – see back matter # 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.eururo.2009.04.020
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EUROPEAN UROLOGY 57 (2010) 891–896
Introduction
pregnancy. No patients with neurogenic detrusor overactivity were included in this study.
Overactive bladder (OAB) is a subgroup of lower urinary tract symptoms (LUTS) defined by the International Continence Society (ICS) as urgency, with or without urgency incontinence (UUI), frequency, and nocturia [1]. The prevalence of OAB symptoms in Europe is reported to be 17.4% in women and 15.6% in men >40 yr, and, overall, 36% had UUI [2]. The National Overactive Bladder Evaluation Programme has reported similar incidence (16% in men and 16.9% in women) in the United States, with 9.3% of women and 2.6% of men having OAB symptoms with UUI. These symptoms had a significant impact on the quality of life, quality of sleep, and mental and social health [3]. The cost of treating clinically significant urinary storage symptoms in the United Kingdom in 2000 was £743 million [4]. It is estimated that the cost of managing OAB in the UK, Italy, Spain, Sweden, and Germany will increase from s4.2 billion in 2000 to s5.2 billion by 2020 [5]. Some 28% of patients presenting with OAB symptoms were prescribed antimuscarinics, 73% of these were referred to secondary specialty care [6], and 25–40% of these patients fail to respond to treatment when urgency incontinence is the primary outcome [3]. Furthermore, 40% of OAB patients discontinue antimuscarinic medications due to adverse events [7]. Intradetrusor injection of botulinum neurotoxin type A (BoNTA) is emerging as the second-line treatment for refractory OAB symptoms secondary to neurogenic detrusor overactivity (NDO) and idiopathic detrusor overactivity (IDO) [8]. As objective measures are poorly representative of or correlated with patient-related outcome measures (PROM), validated subjective instruments are highly recommended for addressing the management of OAB symptoms [9]. Most previous studies have looked at the urodynamic parameters as the primary outcome measures. Werner and colleagues [10] reported ‘‘dry rate’’ based on urodynamics of 54% (14 out of 26) 4 wk after treatment; however, so far, there have been no studies of patient-reported complete continence using validated questionnaires. We, therefore, investigated the patient-reported continence rate after the first intradetrusor injections of BoNTA for treating IDO incontinence.
Urodynamic studies were performed according to the ‘‘good urodynamic practices’’ described by Schafer et al [11]. Urinary tract infections were treated prior to BoNTA injections according to the culture and antibiotic sensitivity report. All patients provided written informed consent before treatment. This study was conducted under a research protocol in the initial 2 yr and had the approval of the local ethics committee. Subsequently, the Trust’s Use of Medicines Committee permitted this off-license treatment for patients with detrusor overactivity. All methods, definitions, and units conform to the standards recommended by the International Continence Society [1].
2.2.
Injection technique
Intradetrusor BoNTA injections were performed in an outpatient setting using the previously described minimally invasive technique [12]. After intraurethral instillation of 20 ml 2% lignocaine gel (Instillagel Farco-Pharma GmbH, Cologne, Germany) and exposure for 2–5 min, a 27G 4-mm long needle (Olympus MAJ-656, KeyMed, Milton Keynes, UK) was passed through the sheath (Olympus NM-101C-0427, KeyMed) of the 2-mm diameter working channel of a flexible cystoscope (Olympus KeyMed) and 200 U of BoNTA (Botox1, Allergan Ltd UK) at 1:10 dilution with 0.9% saline were injected at 20 different sites in the detrusor, sparing the trigone.
2.3.
Patient assessment
Follow-up of bladder diary parameters and urodynamic investigations 4 and 16 wk after BoNTA injections were performed in the early study period (until July 2005) but were not done routinely thereafter since it was apparent the results did not significantly alter the management [13]. Patient-reported continence was assessed using the urgency incontinence and stress incontinence subscales of the Urogenital Distress Inventory (UDI 6) questionnaire (Table 1) [14] before and 4 wk after BoNTA injections. Responses to the UDI 6 subscales—urinary frequency, urgency incontinence, and stress incontinence, which range from 0–3— were transformed to a scale of 0–100 by multiplying by 33.33 according to the recommendation for use of this questionnaire [14]. An outpatient assessment of postvoid residual (PVR) and urine analysis was carried out 2 wk after injections. Written instructions were given to contact the department if bothersome urinary symptoms were a concern. Based on our experience of neurogenic patients’ response to Botox1, we used the criteria for initiating CISC as PVR >100 ml if LUTS persisted. Proven urinary tract infections were treated according to antibiotic sensitivity, but patients were not routinely prescribed prophylactic antibiotics if they were performing CISC. Patients who were on antimuscarinics were advised to reduce or discontinue therapy
2.
Patients and methods
once they noticed improvement in OAB symptoms.
2.1.
Patients
2.4.
Outcome measures
Seventy-four patients with refractory IDO incontinence were treated for
The primary outcome was the patient-reported outcome of complete
the first time once only with intradetrusor injections of 200 U BoNTA in
continence, defined as a score of 0 on both the urgency and stress
this nonrandomised and open-label study between January 2002 and
incontinence subscales of the UDI 6 questionnaire 4 wk after the first
September 2008. The median age of the 74 patients (51 women, 23 men)
BoNTA intradetrusor injection. Secondary outcomes were changes in the
was 56 yr (interquartile range [IQR]: 42–67 yr).
UDI 6 subscales of urinary frequency, urgency incontinence, and stress
Patients with OAB symptoms who were refractory to behavioural
incontinence before and 4 wk after the first injections.
therapy and pharmacotherapy for at least 3 mo were included in the study if standard subtraction filling cystometry revealed detrusor
2.5.
Statistical analysis
overactivity incontinence. Willingness to perform clean intermittent self-catheterisation (CISC) if required after treatment was an important
Data were skewed and are presented as median and IQR. The Wilcoxon
prerequisite. Patients taking anticoagulants or antiplatelets were
signed-rank test was used for comparison of related samples. Unrelated
excluded, as were lactating mothers and women who were planning
samples were compared by applying the Mann-Whitney U test or the
EUROPEAN UROLOGY 57 (2010) 891–896
Table 1 – Items in the Urogenital Distress Inventory Short Form Do you experience, and, if so, how much are you bothered by: 1. Frequent urination 2. Leakage related to feeling of urgency 3. Leakage related to activity, coughing, or sneezing 4. Small amounts of leakage (drops) 5. Difficulty emptying bladder 6. Pain or discomfort in lower abdominal or genital area
chi-square test, as appropriate. A p-value of <0.05 was considered significant. Statistical analysis was performed using SPSS v.16.0 (SPSS Inc, Chicago, IL, USA).
3.
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urgency incontinence scores were reduced significantly from 100 (IQR: 67–100) to 0 (IQR: 0–33) ( p < 0.001), median stress incontinence scores were reduced significantly from 33 (IQR: 0–67) to 0 (IQR: 0–17) ( p < 0.001), and median urinary frequency scores were reduced significantly from 100 (IQR: 100–100) to 33 (IQR: 0–67) ( p < 0.001), respectively (Fig. 2). Two weeks after BoNTA injections, antibiotic treatment for lower urinary tract infection was required in 11 (15%) of the 74 patients. Prior to BoNTA injections all patients voided spontaneously. Following BoNTA treatment, 29 (39%) of 74 patients required CISC. There was no difference ( p = 0.9) between the reported continence rate in those patients performing CISC (52%; 15 of 29) and those who did not (51%; 23 of 45).
Results 4.
All patients had IDO incontinence. According to the patientreported UDI 6 subscales, 33 (45%) patients reported urgency incontinence and 41 (55%) patients mixed incontinence prior to treatment. Four weeks after BoNTA treatment, the proportion of patients reporting complete restoration of continence was 51% (38 of 74). The continence rate was similar ( p = 0.9) for patients who had reported urgency incontinence (52%; 17 of 33) compared to those who had reported mixed incontinence (51%; 21 of 41). There were 36 patients who were still not completely continent; among these, 19 (53%) reported urgency incontinence, 2 (6%) reported stress incontinence, and 15 (42%) reported mixed incontinence (Fig. 1). Age ( p = 0.6) and gender ( p = 0.3) had no influence on the continence rate after BoNTA treatment. Four weeks after intradetrusor BoNTA injections, there was highly significant ( p < 0.001) improvement in the patient-reported urgency incontinence, stress incontinence, and urinary frequency subscales of the UDI 6. Median
Fig. 1 – Patient-reported incontinence before and 4 wk after intradetrusor injections of botulinum neurotoxin type A (BoNT/A) using the subscales of the validated Urogenital Distress Inventory (UDI 6) questionnaire in 74 patients.
Discussion
It has been reported that between 42–87% patients with NDO incontinence become completely continent between CISC after BoNTA treatment [15]. In this open-labelled study of patients with IDO incontinence treated with intradetrusor BoNTA, 51% reported complete restoration of continence 1 mo after treatment. This is in line with the findings of Werner et al [10], who reported a 54% dry rate after 4 wk, although in that study the evidence was based on urodynamic assessment. Besides this notable improvement, we found a significant reduction in the patient-reported urgency incontinence, stress incontinence, and urinary frequency subscales of the UDI 6 questionnaire. Amelioration in OAB symptoms after BoNTA has been reported previously [16–18], and we found that urgency was the earliest and most consistently affected symptom in a mixed group (IDO and NDO) of patients [19]. The standard first-line pharmacological treatment for OAB symptoms is antimuscarinics, the efficacy of this treatment having been shown in systematic reviews [20,21]. Considering that all our patients were refractory to or could not tolerate the side-effects of antimuscarinic therapy, the fact that >50% became completely continent after intradetrusor BoNTA is impressive as it reflects improvement in the patient cohort with the most severe symptoms. Patients’ perceptions affect treatment expectations, and this, in turn, predicts treatment outcomes [22]. Because physicians underestimate the extent to which patients are affected by their symptoms by 25–37% [23], reports of surgical and medical outcomes after treatment should always include independent, validated questionnaires selfadministered by patients to avoid interviewer bias. Objective measures have correlated poorly with patientrelated outcome measures, suggesting that objective and subjective assessments measure different aspects of the patient profile when comparing the efficacy of antimuscarinic receptor antagonists [24], in contrast to the comparison of our subjective results with those of Werner et al [10]. Flynn et al [25], in their pilot study involving seven female patients, also reported a remarkable improvement in subjective outcome measures but without statistically significant changes in urodynamic parameters using
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EUROPEAN UROLOGY 57 (2010) 891–896
mixed incontinence, which is representative of everyday clinical practice. As this assessment was done before and 1 mo after the first BoNTA treatment, the duration for which complete continence lasts and the effect of repeat injections has not been addressed and will need longer term follow-up. 5.
Conclusions
An excellent response in which >50% of patients reported they are completely continent 4 wk after BoNTA treatment reveals the efficacy of this emerging treatment for patients with refractory IDO incontinence. Furthermore, in those in whom complete continence was not achieved, there was a notable and significant reduction in reported urgency incontinence, stress incontinence, and urinary frequency. Author contributions: Clare Fowler had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Khan, Fowler, Kessler. Acquisition of data: Khan, Roosen. Analysis and interpretation of data: Khan, Kessler. Drafting of the manuscript: Khan, Panicker. Fig. 2 – Decline in patient-reported median Urogenital Distress Inventory subscales of frequency, urgency incontinence, and stress incontinence before versus 4 wk after botulinum neurotoxin type A (BoNT/A) injections.
Critical revision of the manuscript for important intellectual content: Kessler, Panicker, Roosen, Fowler. Statistical analysis: Khan, Kessler. Obtaining funding: None. Administrative, technical, or material support: Gonzales, Dasgupta, Elneil. Supervision: Elneil, Dasgupta, Fowler.
150 U of Botox1, whereas Jeffery et al reported improvement in both subjective and objective parameters using 500 U of Dysport [26]. The short versions of the UDI 6 forms were employed in our department, as they are easy to use in clinical practice and in research to characterise the severity of incontinence [14]. It may be argued that some of the patients reporting stress incontinence after BoNTA treatment could have had overflow incontinence due to a high PVR, and this could influence the reported continence status. However, this seems unlikely as CISC was initiated in those with PVR >100 ml, and, furthermore, the reported complete continence was similar in those performing CISC compared to those who did not. Although >50% of our patients with refractory IDO incontinence treated with intradetrusor injections of 200 U BoNTA reported complete restoration of continence 1 mo after treatment, it remains to be established which dose has the best effect with the lowest CISC rate. The ongoing randomised, placebo-controlled, dose-response study (NCT 00168454) may answer this question and guide the decision on optimum dosage. Mixed urinary incontinence was not an exclusion criterion in the present study. After BoNTA treatment, among the 50% incontinent only two patients reported stress incontinence, implying an even higher dry rate if patients with mixed incontinence were excluded. However, being a nonrandomised study without a placebo arm and involving a subjective outcome assessment that is highly individualised, there could be a bias. The patientreported continence rate in our study reflects a diverse group of patients with urgency incontinence as well as those with
Other (specify): None. Financial disclosures: I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Clare Fowler and Prokar Dasgupta are recipients of unrestricted educational grants from Allergan Ltd and have also acted as consultants for Allergan Ltd. Thomas Kessler is supported by a grant from the Swiss National Science Foundation and has acted as consultant for Medtronic. Alexander Roosen is supported by a grant of the German Research Foundation. Sohier Elneil and Clare Fowler are consultants for Medtronic. Clare Fowler was the recipient of an independent research grant from Pfizer, Inc. Funding/Support and role of the sponsor: Allergan Ltd UK was the gratis provider of Botox1 used in the early period of this study.
References [1] Abrams P, Cardozo L, Fall M, et al. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn 2002;21:167–78. [2] Milsom I, Abrams P, Cardozo L, Roberts RG, Thuroff 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;87:760–6. [3] Stewart WF, Van Rooyen JB, Cundiff GW, et al. Prevalence and burden of overactive bladder in the United States. World J Urol 2003;20:327–36.
EUROPEAN UROLOGY 57 (2010) 891–896
[4] Turner DA, Shaw C, McGrother CW, Dallosso HM, Cooper NJ. The cost of clinically significant urinary storage symptoms for
895
activity/neurogenic overactive bladder: a systematic literature review. Eur Urol 2008;53:275–87.
community dwelling adults in the UK. BJU Int 2004;93:1246–52.
[16] Kalsi V, Apostolidis A, Popat R, Gonzales G, Fowler CJ, Dasgupta
[5] Reeves P, Irwin D, Kelleher C, et al. The current and future burden
P. Quality of life changes in patients with neurogenic versus
and cost of overactive bladder in five European countries. Eur Urol
idiopathic detrusor overactivity after intradetrusor injections of
2006;50:1050–7.
botulinum neurotoxin type A and correlations with lower urin-
[6] Odeyemi IA, Dakin HA, O’Donnell RA, Warner J, Jacobs A, Dasgupta P. Epidemiology, prescribing patterns and resource use associated with overactive bladder in UK primary care. Int J Clin Pract 2006;60:949–58. [7] Kelleher CJ, Cardozo LD, Khullar V, Salvatore S. A medium-term analysis of the subjective efficacy of treatment for women with detrusor instability and low bladder compliance. Br J Obstet Gynaecol 1997;104:988–93. [8] Apostolidis A, Dasgupta P, Denys P, et al. Recommendations on the use of botulinum toxin in the treatment of lower urinary tract disorders and pelvic floor dysfunctions: a European consensus report. Eur Urol 2009;55:100–20. [9] Abrams P, Artibani W, Gajewski JB, Hussain I. Assessment of treatment outcomes in patients with overactive bladder: importance of objective and subjective measures. Urology 2006;68:17–28.
ary tract symptoms and urodynamic changes. Eur Urol 2006; 49:528–35. [17] Sahai A, Khan MS, Dasgupta P. Efficacy of botulinum toxin-A for treating idiopathic detrusor overactivity: results from a single center, randomized, double-blind, placebo controlled trial. J Urol 2007;177:2231–6. [18] Schmid DM, Sauermann P, Werner M, et al. Experience with 100 cases treated with botulinum-A toxin injections in the detrusor muscle for idiopathic overactive bladder syndrome refractory to anticholinergics. J Urol 2006;176:177–85. [19] Kalsi V, Apostolidis A, Gonzales G, Elneil S, Dasgupta P, Fowler CJ. Early effect on the overactive bladder symptoms following botulinum neurotoxin type A injections for detrusor overactivity. Eur Urol 2008;54:181–7. [20] Chapple CR, Khullar V, Gabriel Z, Muston D, Bitoun CE, Weinstein D.
[10] Werner M, Schmid DM, Schussler B. Efficacy of botulinum-A toxin in
The effects of antimuscarinic treatments in overactive bladder: an
the treatment of detrusor overactivity incontinence: a prospective
update of a systematic review and meta-analysis. Eur Urol 2008;
nonrandomized study. Am J Obstet Gynecol 2005;192:1735–40.
54:543–62.
[11] Schafer W, Abrams P, Liao L, et al. Good urodynamic practices:
[21] Novara G, Galfano A, Secco S, et al. A systematic review and meta-
uroflowmetry, filling cystometry, and pressure-flow studies. Neu-
analysis of randomized controlled trials with antimuscarinic drugs
rourol Urodyn 2002;21:261–74.
for overactive bladder. Eur Urol 2008;54:740–64.
[12] Harper M, Popat RB, Dasgupta R, Fowler CJ, Dasgupta P. A minimally
[22] Marschall-Kehrel D, Roberts RG, Brubaker L. Patient-reported out-
invasive technique for outpatient local anaesthetic administration
comes in overactive bladder: the influence of perception of condition
of intradetrusor botulinum toxin in intractable detrusor overactivity. BJU Int 2003;92:325–6. [13] Popat R, Apostolidis A, Kalsi V, Gonzales G, Fowler CJ, Dasgupta P. A comparison between the response of patients with idiopathic detrusor overactivity and neurogenic detrusor overactivity to the first intradetrusor injection of botulinum-A toxin. J Urol 2005;174:984–9.
and expectation for treatment benefit. Urology 2006;68:29–37. [23] Rodriguez LV, Blander DS, Dorey F, Raz S, Zimmern P. Discrepancy in patient and physician perception of patient’s quality of life related to urinary symptoms. Urology 2003;62:49–53. [24] Abrams P, Andersson KE. Muscarinic receptor antagonists for overactive bladder. BJU Int 2007;100:987–1006.
[14] Uebersax JS, Wyman JF, Shumaker SA, McClish DK, Fantl JA. Short
[25] Flynn MK, Webster GD, Amundsen CL. The effect of botulinum-A
forms to assess life quality and symptom distress for urinary
toxin on patients with severe urge urinary incontinence. J Urol
incontinence in women: the Incontinence Impact Questionnaire and the Urogenital Distress Inventory. Continence Program for
2004;172:2316–20. [26] Jeffery S, Fynes M, Lee F, Wang K, Williams L, Morley R. Efficacy and
Women Research Group. Neurourol Urodyn 1995;14:131–9.
complications of intradetrusor injection with botulinum toxin A in
[15] Karsenty G, Denys P, Amarenco G, et al. Botulinum toxin A (Botox1)
patients with refractory idiopathic detrusor overactivity. BJU Int
intradetrusor injections in adults with neurogenic detrusor over-
Editorial Comment on: Complete Continence after Botulinum Neurotoxin Type A Injections for Refractory Idiopathic Detrusor Overactivity Incontinence: Patient-Reported Outcome at 4 Weeks Mehmet Kilinc, Selcuk Guven Department of Urology, Meram Faculty of Medicine, Selcuk University, 42080 Konya, Turkey [email protected] Khan and co-authors investigated the change in patient-reported continence rate after intradetrusor botulinum neurotoxin A (BoNTA) injections for treating idiopathic detrusor overactivity (IDO) incontinence [1]. Assessment of treatment outcomes is a considerable problem of IDO patients. Objective measures of treatment
2007;100:1302–6.
efficacy (eg, urodynamic studies, bladder diary variables) are not always predictive of subjective outcomes, which are influenced by a patient’s priorities and lifestyle [2]. Thus, the patient-reported outcomes are relevant to clinical practice and should be used with objective measures to better evaluate the effects of treatment on IDO patients’ perceptions of health-related quality of life. As there have not yet been any studies on this issue using validated questionnaires, and thus no data are available, the outcome of the present study gains further importance. A number of limitations, however, should be noted. First, the major limitation of this study is a nonrandomised design. Randomised placebo controlled trials are needed to confirm the outcomes mentioned in the study. Second,
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the authors also included the mixed-incontinence patients in the study. The pathophysiological interactions and the clinical evaluation of mixed incontinence are different; thus, although the outcome measures rely on subjective patient-reported questionnaires, stress and urge incontinence should be described separately rather than as a single dimension [3]. Although treatment of IDO patients with BoNTA injections has gained increasing acceptance as a secondline option in management of IDO incontinence, several mysteries remain regarding:
Further large randomised placebo-controlled trials are needed to elucidate the ideal conditions of the BoNTA injections for the IDO patients.
References [1] Khan S, Panicker J, Roosen A, et al. Complete continence after botulinum neurotoxin type A injections for refractory idiopathic detrusor overactivity incontinence: patient reported outcome at 4 weeks. Eur Urol 2010;57:891–6. [2] Abrams P, Artibani W, Gajewski JB, Hussain I. Assessment of treatment outcomes in patients with overactive bladder: importance of
Injection technique, injection site, and number Optimal dose, dosing interval, and best minimal dosage to avoid voiding difficulty Long-term follow-up, duration of continence effect, and the effect of repeat injections Post-treatment follow-up, the number and timing of postresidual voiding assessments, and threshold to begin clean intermittent self-catheterisations.
Editorial Comment on: Complete Continence after Botulinum Neurotoxin Type A Injections for Refractory Idiopathic Detrusor Overactivity Incontinence: Patient-Reported Outcome at 4 Weeks Antonella Giannantoni Department of Urology and Andrology, University of Perugia, Policlinico Monteluce, Perugia, Italy [email protected] In the present article, Khan and co-authors investigated the patient-reported continence rate after the first intradetrusorial injection of botulinum A toxin (BoNTA) in the treatment of idiopathic detrusor overactivity (IDO) [1]. They found that intradetrusorially injected BoNTA not only improved frequency of micturition and urinary urgency but also eliminated urge incontinence in >50% of patients at 4 wk after treatment. As a complication, 39% of these patients required clean intermittent self-catheterization (CISC) to empty their bladders completely after treatment. The main contribution of the present article relies on the use, for the first time, of a validated questionnaire in evaluating the response of IDO patients to BoNTA treatment. Only self-administered validated questionnaires can exactly evaluate the extent to which patients
objective and subjective measures. Urology 2006;68(Suppl):17–28. [3] Brubaker L, Stoddard A, Richter H, et al. Mixed incontinence: comparing definitions in women having stress incontinence surgery. Neurourol Urodyn 2009;28:268–73.
DOI: 10.1016/j.eururo.2009.04.021 DOI of original article: 10.1016/j.eururo.2009.04.020
are affected by their symptoms and whether those symptoms are alleviated by a particular treatment. The major result consists of the fact that all of the patients in the study were refractory to or could not tolerate the side effects of anticholinergic treatment. Thus, the high continence rate is really impressive, as it was obtained in subjects with more severe symptoms. Nevertheless, a question still remains about which dose of BoNTA has the main effect with the lowest CISC rate. This issue is important for future research in this field of application. In all of these respects, the present article represents an important contribution to the growing literature regarding the use of BoNTA in functional urology.
References [1] Khan S, Panicker J, Roosen A, et al. Complete continence after botulinum neurotoxin type A injections for refractory idiopathic detrusor overactivity incontinence: patient-reported outcome at 4 weeks. Eur Urol 2010;57:891–6.
DOI: 10.1016/j.eururo.2009.04.022 DOI of original article: 10.1016/j.eururo.2009.04.020