Cost-effectiveness analysis of sacral neuromodulation and botulinum toxin A treatment for patients with idiopathic overactive bladder

Study Type – Therapy (economic analysis) Level of Evidence 1b

OBJECTIVE

To assess and compare the costs and effects value of either starting with sacral neuromodulation (SNM) or botulinum toxin A (BTX) treatment in patients with refractory idiopathic overactive bladder from a societal perspective.

MATERIALS AND METHODS

An economic model comparing SNM with BTX was developed. A clinical relevant effect (i.e. success) was defined as 50% or greater reduction in incontinence episodes or urgency frequency symptoms. Information on the clinical effectiveness of the two treatments and on the course of the disease with the two treatments were based primarily on published literature and, when required, on expert opinion. Both treatments were assumed to be performed under general anaesthesia and, for SNM treatment, first‐stage tined lead test was used. All costs were based on national data from the year 2008. Analyses from the societal perspective were conducted for a 5‐year duration. Costs were discounted at 4% and effects at 1.5%. In addition, different modelling scenarios were used to see determine any changes in the results obtained.

RESULTS

Starting with SNM resulted in a higher quality adjusted life year (QALY) gain (differenceof 0.23) and a higher cost (difference of €6428) compared to starting with BTX. The corresponding incremental cost‐effectiveness ratio was €27 991/QALY. The probability of this ratio being cost effective (e.g. under €40 000/QALY) is 88%. SNM starts to be cost‐effective after 4 years. SNM was not cost‐effective in some other scenarios, such as when BTX was conducted under local anaesthesia or when peripheral nerve evaluation or bilateral testing was used for SNM.

CONCLUSIONS

Starting with SNM, treatment is cost‐effective after 5 years compared to BTX. However, in some scenarios, such as the use of local anaesthesia for BTX treatment and SNM peripheral nerve evaluation or bilateral test, SNM was not cost‐effective.     

Use and mechanism of botulinum toxin in overactive bladder treatment

Overactive bladder is very frequent in central neurogenic patients; it is a major cause of refractory incontinence despite anticholinergic treatment. In non-neurogenic patients it results in very distressing symptoms that associate urgency with or without incontinence and frequency. Botulinum toxin A is a well known agent used previously in the treatment of striated muscle spasmodism, which blocks the release of acetylcholine from nerve endings and neuro-muscular transmission. Its recent use in urology revealed a dramatic improvement in clinical and urodynamic parameters of the overactive bladder, associated with a long lasting effect over 6 to 9 months and an excellent tolerance. In neurogenic patients, the efficacy of botulinum injection was demonstrated over a placebo control group. Toxin was injected at 20 to 30 different sites in the detrusor muscle, with cystoscopy guidance. Recent studies showed a sub-epithelial mechanism of action on neuropeptides, which could explain an inhibitory effect of both efferent and afferent arms of the micturition reflex. Further studies remain necessary regarding the respective doses of Dysport and Botox toxin, selection of patients, combination with anticholinergic treatment, effects of repeated injections.     

Repeated botulinum toxin type A injections for refractory overactive bladder: medium-term outcomes, safety profile, and discontinuation rates

Background

Efficacy and safety of botulinum toxin type A (BoNTA) injection is supported by level 1 evidence, but data regarding repeated injections are limited in patients with refractory overactive bladder (OAB) and idiopathic detrusor overactivity (IDO).

Objectives

Describe medium-term outcomes and discontinuation rates for patients adopting repeated BoNTA as a management strategy for IDO.

Design, setting, and participants

Prospective data from a single centre were collected from the first 100 patients.

Intervention

Bladder injection of BoNTA (predominantly 200 U onabotulinumtoxinA; Allergan Ltd., Marlow, Buckinghamshire, UK) in an outpatient setting.

Measurements

OAB symptoms, quality of life, discontinuation rates, interinjection interval, and adverse events were recorded. Data comparisons were performed using a generalised linear model or a chi-square test where appropriate.

Results and limitations

Two hundred seven injections were performed in 100 patients. All patients had 1 injection, 53 had a total of 2, 20 had 3, 13 had 4, 10 had 5, 5 had 6, 3 had 7, 1 had 8, 1 had 9, and 1 had 10 injections. Statistics were applied up to five repeated injections. A statistically significant reduction in frequency, urgency, and urge urinary incontinence were seen following the first BoNTA injection compared to baseline. This improvement was maintained after repeated injections and was not statistically different when comparing differences between injections. Thirty-seven patients stopped treatment after the first two injections; thereafter, dropouts were rare. The most common reasons for discontinuing treatment were poor efficacy (13%) and clean intermittent self-catheterisation (CISC)–related issues (11%). The incidence of CISC after the first injection was 35%. Bacteriuria was detected in 21% of patients. The mean interinjection interval was 322 d. Limitations included the concurrent use of antimuscarinic drugs in some patients.

Conclusions

BoNTA can provide a safe and effective medium-term management option for patients with refractory IDO. The most common reasons cited for stopping treatment were poor efficacy and CISC-related issues.     

Role of botulinum toxin-A in refractory idiopathic overactive bladder patients without detrusor overactivity

Background  

To evaluate the efficacy of intradetrusor botulinum toxin-A (BTX-A) in idiopathic overactive bladder patients (OAB) refractory to anti-muscarinic therapy, without detrusor overactivity (DOA) on urodynamics.     

Intravesical botulinum toxin for overactive bladder syndrome without detrusor overactivity

ObjectiveTo report our experience of intravesical botulinum toxin for idiopathic overactive bladder syndrome (OAB) without detrusor overactivity (DOA) on urodynamic assessment.Patients and methodsData regarding presentation, diagnosis, urodynamic findings, date and dose of treatment, and outcomes were recorded prospectively for 94 patients undergoing intravesical botulinum toxin injection for idiopathic overactive bladder syndrome at our institution. The cohort included 19 patients without DOA on urodynamics. A positive response to treatment was defined as patient-reported improvement without the need for further treatment. ICIQ-OAB and UI scores, and bladder diary parameters were also recorded. Rates of urinary retention requiring intermittent or indwelling catheterisation were noted.ResultsThe overall response rate to treatment was 82% (n = 94). Patients without DOA (n = 19) had a response rate of 89%, which compared favourably with a response rate of 81% in patients with DOA (n = 75).Overall, 29% of patients who were voiding normally prior to treatment required intermittent self-catheterisation after the procedure. The requirement for self-catheterisation did not appear to be influenced by urodynamic findings.ConclusionThese preliminary, non-randomised data suggest that intravesical botulinum toxin injection may be efficacious in patients with OAB symptoms without DOA. Further evaluation by means of a randomised, controlled trial is suggested.     

Treatment of overactive bladder with botulinum toxin type B: a pilot study

The purpose of this study was to determine the efficacy and safety of botulinum toxin type B (BTX-B/Myobloc) in the treatment of patients with overactive bladder. This open-label dose-escalation study enrolled 15 female patients with urinary frequency with or without incontinence. The BTX-B doses used in this study were 2500, 3750, 5000, 10 000 and 15 000 units. Response was defined as a subjective improvement in frequency, urgency and incontinence symptoms. A paired t-test of the pre/post frequency difference indicates that these 15 patients experienced an average of 5.27 fewer frequency episodes per day after treatment with BTX-B. The p value for the paired t-test was <0.001. The longest duration effect was 3 months using 10 000–15 000 units of BTX-B. The correlation between dose and duration was very significant, with a correlation coefficient = 0.96, p<0.001. Based on these findings, we feel the use of botulinum toxin to treat patients with overactive bladder warrants further study.Abbreviations OAB Overactive bladder Editorial Comment: The authors discuss the short-term efficacy of botulinum toxin type B in patients with overactive bladder. An attempt is made to identify the highest safe dosage, but the data presented are limited and a final recommendation regarding this requires further study. The high correlation found between dosage and duration of efficacy is very interesting and clinically relevant. Such a relationship has not been previously described for botulinum toxin type A. The duration of response is concerning and does appear to be significantly lower than that previously published and what I have personally experienced with botulinum toxin type A. Although this may be due to variations in injection technique, it may also be a result of the type of toxin used. I agree that longer-term and comparative data are warranted.     

Experience with 100 cases treated with botulinum-A toxin injections in the detrusor muscle for idiopathic overactive bladder syndrome refractory to anticholinergics

PURPOSE: In this prospective, nonrandomized, ongoing study we evaluated the efficacy and safety of botulinum-A toxin injections in the detrusor muscle to treat patients with idiopathic overactive bladder resistant to conventional treatment, such as anticholinergic drugs. MATERIALS AND METHODS: A total of 23 men and 77 women with a mean age of 63 years (range 24 to 89) with nonneurogenic overactive bladder, including urgency-frequency syndrome, and incontinence despite the administration of maximal doses of anticholinergics were consecutively treated with injections of 100 U botulinum-A toxin in the detrusor muscle at 30 sites under cystoscopic guidance. Micturition diary, full urodynamics, neurological status and urine probes were performed in all participants before treatment. Bladder biopsies were done only in cases of suspected bladder fibrosis or unclear findings. Special attention was given to reflex volume, maximal bladder capacity, detrusor compliance, post-void residual urine, urgency and frequency/nocturia. Clinical, urodynamic and quality of life assessments were performed at baseline, and 4, 12 and 36 weeks after botulinum-A toxin treatment. RESULTS: Overall after 4 and 12 weeks 88% of our patients showed significant improvement in bladder function in regard to subjective symptoms, quality of life and urodynamic parameters (p <0.001). Urgency disappeared in 82% of the patients and incontinence resolved in 86% within 1 to 2 weeks after botulinum-A toxin injections. Mean frequency decreased from 14 to 7 micturitions daily (-50%) and nocturia decreased from 4 to 1.5 micturitions. Mean maximal bladder capacity increased 56% from 246 to 381 ml, mean detrusor compliance increased from 24 to 41 ml/cm H(2)O and pretreatment detrusor instability (mean reflex volume 169 ml) resolved in 74% of patients. Mean volume at first desire to void increased from 126 to 212 ml and mean urge volume increased from 214 to 309 ml. There were no severe side effects except temporary urine retention in 4 cases. Only in 8 patients was the clinical benefit poor and analysis revealed preoperative low detrusor compliance. Mean efficacy duration +/- SD was at least approximately 6 +/- 2 months and then symptoms began to increase. CONCLUSIONS: Our results show that intradetrusor botulinum-A toxin injections may be an efficient and safe treatment option in patients with severe overactive bladder resistant to all conventional treatments.     

Non-invasive evaluation of botulinum-A toxin treatment efficacy in children with refractory overactive bladder

Objective

We aimed to evaluate the efficacy and safety of intravesical onabotulinum toxin A (onaBoNTA) injections for the treatment of children diagnosed with refractory overactive bladder (OAB) by using non-invasive methods.

Methods

A total of 31 pediatric patients with a mean age of 10.2 years received intravesical onaBoNTA injection at the dose of 10 U/kg (max: 200 U). Twenty-one patients who failed to respond to the first injection, received second injection 6 months after the first one. The patients were retrospectively evaluated after the 1st and the 2nd injections by means of standardized questionnaire forms and voiding diary records.

Results

In the 6-month follow-up, 10 patients (32.2%) were determined to have full response after the first injection. The number of patients with partial response and no response were found to be 15 (48.4%) and 6 (19.4%), respectively. The mean value of Dysfunctional Voiding and Incontinence Symptom Score (DVISS) of the patients with full response was 8.5 before the injection, which decreased to 1 at 6-month follow-up and to 0.5 at 12-month follow-up (p?<?0.001). Twenty-one patients without full response after the first injection received a second injection 6 months after the first one. Full response was achieved in 9 (42.9%) of the 21 patients who had a second injection, but only partial response was achieved in 9 (42.9%). Three (14.3%) of the remaining patients did not respond to the second injection either. 1-year follow-up evaluations revealed that the rates of the full response, partial response, and no response were 61.3, 29, and 9.7%, respectively.

Conclusions

Based on our results, onaBoNTA therapy is an effective and reliable second-line off-label therapy in the management of patients with non-neurogenic OAB that is refractory to medical therapy. Asking the patients/guardians to fill out a standardized questionnaire form before and after the therapy enables easy and non-invasive assessment of the response to the therapy.