Results of a prospective,multicenter study evaluating quality of life,safety, and efficacy of sacral neuromodulation at twelve months in subjects with symptoms of overactive bladder

Aims

This prospective, multicenter post‐approval study evaluated the success rate of sacral neuromodulation (SNM) with the InterStim® System at 12‐months. Subjects with bothersome symptoms of overactive bladder (OAB) including urinary urge incontinence (UI) or urgency‐frequency (UF), who failed at least one anticholinergic medication and had at least one not tried were included.

Methods

Subjects with successful test stimulation received an SNM implant. Therapeutic success (≥50% improvement in average leaks/day or voids/day or a return to normal voiding frequency [<8 voids/day]) and quality of life through 12 months were evaluated for implanted subjects.

Results

Of the 340 subjects that went through test stimulation, 272 were implanted with SNM. Of these, 91% were female, mean age was 57, UI subjects had 3.1 ± 2.7 leaks/day, UF subjects had 12.6 ± 4.5 voids/day. The analysis which includes all implanted subjects with diary data at baseline and 12 months showed an OAB therapeutic success rate of 85% at 12 months. UI subjects had a mean reduction of 2.2 ± 2.7 leaks/day; UF subjects had a mean reduction of 5.1 ± 4.1 voids/day (both P < 0.0001). Subjects showed significant improvement from baseline in all measures of ICIQ‐OABqol (all P < 0.0001). 80% of subjects reported improved changes in their urinary symptom interference at 12 months. Device‐related adverse events occurred in 16% (56/340) of subjects during test stimulation and 30% (82/272) of subjects post‐implant.

Conclusions

This multicenter study shows SNM is safe and effective and results in improved outcomes through 12 months in subjects with OAB symptoms, without requiring failure of all medications. Neurourol. Urodynam. 35:246–251, 2016. © 2014 The Authors. Neurourology and Urodynamics published by Wiley Periodicals, Inc.     

Short- and long-term efficacy of solifenacin treatment in patients with symptoms of mixed urinary incontinence

OBJECTIVE: To evaluate urinary symptom relief in women with mixed urinary incontinence (MUI) treated for up to 52 weeks with solifenacin succinate for overactive bladder (OAB), as MUI is a complex and distressing condition reported by about a third of incontinent women, and with confirmed efficacy in OAB-related urge incontinence, anticholinergic agents are a reasonable therapeutic option for such women. PATIENTS AND METHODS: Patients with OAB (mean of > or = 8 voids/24 h, plus > or = 1 incontinence episode or > or = 1 urgency episode/24 h) were pooled from four studies. A subgroup of 1041 patients reporting MUI at baseline were evaluated over 12 weeks in a double-blind, placebo-controlled study, and up to a further 40 weeks in 433 in an open-label solifenacin treatment (5 mg and 10 mg). Voiding frequency, episodes of incontinence and urgency, and volume voided per void, were collected from voiding diaries completed during the 3 days before each study visit. RESULTS: Patients with a history of MUI treated with solifenacin for up to 12 weeks had statistically significant reductions in voiding frequency and episodes of incontinence and urgency vs placebo. In all, 43% and 49% (at 5 mg and 10 mg, respectively) of patients with a history of MUI regained continence after 12 weeks, vs 33% with placebo. Among patients in the open-label study with mixed symptoms, 52% reported regaining continence, and 34% reported resolution of symptomatic urgency based on diary reporting at study end. Sustained improvements in quality of life and high satisfaction ratings accompanied symptom improvements. CONCLUSIONS: Significant reductions in OAB-related frequency, incontinence and urgency were reported after 12 weeks of solifenacin treatment in patients with a history of MUI. Symptom improvement in this subgroup was maintained during long-term treatment. These findings support the therapeutic potential of solifenacin for treating symptoms of MUI and the need to re-evaluate classically defined MUI.     

A validated patient reported measure of urinary urgency severity in overactive bladder for use in clinical trials

PURPOSE: Overactive bladder (OAB) is a syndrome consisting of urinary urgency with or without urge incontinence, usually with increased urinary frequency and nocturia. In response to current limitations in OAB clinical research a new patient reported measure of urgency severity associated with OAB has been developed, namely the Indevus Urgency Severity Scale (IUSS). We report the measurement properties of the IUSS. MATERIALS AND METHODS: Validation study data were collected alongside a phase III clinical trial of 20 mg trospium chloride twice daily vs placebo in patients with OAB associated with urge incontinence. We evaluated IUSS item variability, known group, content, criterion and construct validity, test-retest reliability, responsiveness and respondent burden. RESULTS: A total of 658 patients were evaluated at baseline and 579 were reevaluated at week 12. IUSS demonstrated good item variability. Greater urgency severity was associated with increased symptom bother and worse health related quality of life, as measured by the OAB QOL questionnaire. IUSS had a significant positive association with essential clinical and quality of life outcomes, demonstrating content validity. IUSS was highly responsive to a decrease in the average number of patient toilet voids per 24 hours to 7 or fewer toilet voids and average urge incontinence episodes per 24 hours to zero. It discriminated between patients who had above and below the median number of toilet voids and urge incontinence episodes per 24 hours. IUSS also had good test-retest reliability and content validity, and it created minimal respondent burden. CONCLUSIONS: IUSS is a validated patient reported measure of urgency severity for collecting event specific information in the context of a clinical trial.     

Efficacy and tolerability of tolterodine extended-release in continent patients with overactive bladder and nocturia

OBJECTIVE: To evaluate the clinical efficacy and tolerability of tolterodine extended-release (ER) in continent patients with overactive bladder (OAB) and nocturia. PATIENTS AND METHODS: A post hoc analysis was conducted of data from a 12-week, double-blind study of 850 patients randomized to tolterodine ER (4 mg once daily) or placebo, taken within 4 h of going to bed. Patients with a mean of > or = 8 voids/24 h were enrolled, including a mean of > or = 2.5 voids/night. Patients completed 7-day voiding diaries, and for each void an urgency rating was assessed using a 5-point scale (1, none; 5, urgency incontinence); 24-h voids were categorized by urgency rating: total (1-5), non-OAB (1-2), OAB (3-4), and severe OAB (4-5) voids. All adverse events were recorded. RESULTS: The post hoc analysis included 513 patients (243 placebo; 270 tolterodine ER; 58% men) who were continent at baseline; 47% of 24-h voids were classed as non-OAB, and 12% as severe OAB. After 12 weeks of treatment, tolterodine ER significantly reduced mean urgency rating and 24-h OAB, severe OAB, and total voids vs placebo. Tolterodine ER did not affect normal, non-OAB voids, and there were no significant adverse events related to voiding. Other than dry mouth (tolterodine ER, 9% vs placebo, 2%), all the adverse events were reported in <3% of patients; <2% of patients receiving tolterodine ER withdrew because of adverse events. CONCLUSIONS: In continent patients with OAB, tolterodine ER significantly improved urgency rating and reduced 24-h OAB, severe OAB, and total voids, suggesting that it is an effective and well-tolerated treatment option for this subpopulation. More studies are needed to better understand the clinical efficacy of tolterodine ER in this under evaluated group of OAB patients without incontinence.     

Tolterodine is equally effective in patients with mixed incontinence and those with urge incontinence alone

OBJECTIVE: To examine the efficacy of tolterodine, an antimuscarinic agent with a bladder-selective profile, in patients with mixed incontinence (MI, stress and urge) compared with patients with urge incontinence (UI) alone. PATIENTS AND METHODS: The study included 239 patients with MI (urge predominating) and 755 with urge incontinence alone from a single-blind, multicentre trial of 1380 patients (80% female) with an overactive bladder. Those completing the trial were analysed 'per-protocol'. After a 7-day washout and a 3-day run-in to collect baseline information, patients were treated with tolterodine twice daily for 16 weeks. The two groups were compared for incontinence episodes/24 h, voiding frequency, nocturia episodes and pad usage after 16 weeks of treatment. RESULTS: After 16 weeks the median changes from baseline for all voiding variables were statistically significant for the MI and the UI groups (P < 0.001), with no apparent significant between-group differences. The median percentage reduction in incontinence episodes from baseline was 67% for the MI and 75% for the UI groups (P = 0.39). 'Dry' rates for the MI and UI groups at the end of the study were 39% (66/171) and 44% (243/552), respectively, whilst 24% of patients in each group (MI 40/170; UI 130/551) achieved a voiding pattern of < 8 voids/24 h. 'Cure' rates for nocturia and the reduction in the number of patients not using pads used were also similar between the groups. CONCLUSION: Tolterodine is as effective in reducing leakage and other symptoms of an overactive bladder in patients with MI as it is in patients with UI alone.     

Results of sacral neuromodulation therapy for urinary voiding dysfunction: outcomes of a prospective, worldwide clinical study

PURPOSE: This 5-year, prospective, multicenter trial evaluated the long-term safety and efficacy of sacral neuromodulation in patients with refractory urge incontinence, urgency frequency and retention. MATERIALS AND METHODS: A total of 17 centers worldwide enrolled 163 patients (87% female). Following test stimulation 11 patients declined implantation and 152 underwent implantation using InterStim. Of those treated with implantation 96 (63.2%) had urge incontinence, 25 (16.4%) had urgency frequency and 31 (20.4%) had retention. Voiding diaries were collected annually for 5 years. Clinical success was defined as 50% or greater improvement from baseline in primary voiding diary variable(s). RESULTS: Data for all implanted cases were reported. For patients with urge incontinence mean leaking episodes per day decreased from 9.6 +/- 6.0 to 3.9 +/- 4.0 at 5 years. For patients with urgency frequency mean voids per day decreased from 19.3 +/- 7.0 to 14.8 +/- 7.6, and mean volume voided per void increased from 92.3 +/- 52.8 to 165.2 +/- 147.7 ml. For patients with retention the mean volume per catheterization decreased from 379.9 +/- 183.8 to 109.2 +/- 184.3 ml, and the mean number of catheterizations decreased from 5.3 +/- 2.8 to 1.9 +/- 2.8. All changes were statistically significant (p <0.001). No life threatening or irreversible adverse events occurred. In 102 patients 279 device or therapy related adverse events were observed. At 5 years after implantation 68% of patients with urge incontinence, 56% with urgency frequency and 71% with retention had successful outcomes. CONCLUSIONS: This long-term study demonstrates that InterStim therapy is safe and effective for restoring voiding in appropriately selected cases refractory to other forms of treatment.     

A novel surgical technique for implanting a new electrostimulation system for treating female overactive bladder: a preliminary report

OBJECTIVE: To assess the results of peripheral electrostimulation of pelvic floor muscles in patients with overactive bladder (OAB) symptoms, and to describe a novel surgical technique for inserting a specially designed implantable electrostimulator which can deliver different forms of muscle stimulation through a para-urethral electrode. PATIENTS AND METHODS: The study included seven women with OAB (mean age 59 years) who had frequency (including nocturia), urgency and urge incontinence for > or = 1 year, and in whom conventional treatment failed. The antepubic technique was used to implant the electrostimulator and a para-urethral electrode. The patients' urinary symptoms and quality of life (King's College Hospital incontinence questionnaire) were compared before and after surgery, and possible complications monitored. RESULTS: The mean (range) follow-up was 14.5 (13-17) months in six and 10 months in the seventh patient (stimulator removed because of infection). The mean (range) frequency of 15 (13-23) voids/24 h before surgery decreased to 9 voids/24 h (i.e. by 40%) afterward. All patients had leakage episodes because of urgency (4-15 times/day) before surgery, which ceased in five afterward; these patients used no further pads. In the remaining two patients urgency incontinence continued after surgery, but with significantly fewer leakage episodes, from 15 and 12 per day before to 6.7 and 4 afterward, respectively. The mean degree of urgency (graded 0-3) decreased from 2 to 1.4 after surgery, and quality of life improved significantly. Urodynamic studies showed a greater mean maximum detrusor capacity, from 135 mL before to 189 mL after implanting the stimulator. CONCLUSIONS: The good results (over a follow-up of 1 year) in patients with OAB symptoms treated by the present electrostimulator should encourage further clinical studies in such patients. A trial to evaluate the efficacy of pelvic floor muscle electrostimulation in a broad spectrum of diseases of the lower urinary tract causing symptoms similar to OAB has been started.     

Does concomitant stress incontinence alter the efficacy of tolterodine in patients with overactive bladder?

PURPOSE: Muscarinic antagonists such as tolterodine are the treatment of choice for overactive bladder (OAB). We determined the impact of concomitant stress incontinence (SI) on the therapeutic effects of tolterodine in patients with OAB with and without concomitant SI. MATERIALS AND METHODS: Data from an open label, observational study involving 2,250 patients with OAB symptoms were analyzed for baseline frequency, urgency and incontinence, and alterations in these symptoms while on 12-week treatment with 2 mg tolterodine twice daily. Data are shown as the mean +/- SD. The statistical significance of differences in treatment effects was determined by multiple regression analysis, adjusting for gender, age and baseline symptom intensity. RESULTS: Concomitant I to III degree SI according to the Stamey grading was present in 31%, 15% and 2% of patients, respectively, and it was associated with increasing basal incontinence, although only III degree SI was associated with greater baseline frequency or urgency. In the overall group tolterodine decreased frequency, urgency and urge incontinence from 12.4 +/- 4.3 to 7.7 +/- 2.7, 8.4 +/- 5.1 to 2.0 +/- 3.0 and 3.4 +/- 4.2 to 0.8 +/- 2.0 episodes daily, respectively. On multiple linear regression analysis I and II degree SI had a minor, if any, effect on this improvement, while III degree SI was statistically associated with a smaller decrease in frequency (by 1.4 +/- 0.4 micturitions daily, p = 0.0002) and incontinence (by 2.1 +/- 0.3 episodes daily, p < 0.0001) but with similar alterations in the number of urge episodes. CONCLUSIONS: Concomitant I or II degree SI has little effect on the efficacy of tolterodine in OAB cases. Only patients with concomitant III degree SI have significantly less improvement.     

Randomized, double-blind placebo- and tolterodine-controlled trial of the once-daily antimuscarinic agent solifenacin in patients with symptomatic overactive bladder

OBJECTIVE: To assess in a phase 3a trial the efficacy of solifenacin succinate, a once-daily oral antimuscarinic agent in development at 5-mg and 10-mg dosage strengths, for the treatment of overactive bladder (OAB) (Yamanouchi Pharmaceutical Co. Ltd, Tokyo, Japan) compared with placebo in patients with symptoms of OAB, i.e. urgency, incontinence, and frequency, with additional objectives being to assess the safety and tolerability of solifenacin and to compare the efficacy and safety of solifenacin with tolterodine 2 mg twice daily. PATIENTS AND METHODS: The study was an international, multicentre, randomized, double-blind, tolterodine- and placebo-controlled trial conducted at 98 centres. Adult patients with symptomatic OAB for > or = 3 months were eligible; after a single-blind 2-week placebo run-in period patients were randomized equally to a 12-week double-blind treatment with either tolterodine 2 mg twice daily, placebo, solifenacin 5 mg or 10 mg once daily. Efficacy variables included change from baseline in the mean number of urgency, incontinence and urge incontinence episodes, and change from baseline in voids/24 h and mean volume voided/void. RESULTS: In all, 1281 patients were enrolled, 1081 randomized and 1077 treated; 1033 were evaluated for efficacy. Compared with placebo, the change from baseline (-1.41, -32.7%) in the mean number of urgency episodes per 24 h was statistically significantly lower with solifenacin 5 mg (-2.85, -51.9%) and 10 mg (-3.07, -54.7%; both P < 0.001), but not with tolterodine (-2.05, -37.9%; P = 0.0511). There was a statistically insignificant decrease in episodes of incontinence with tolterodine (-1.14; P = 0.1122) but a significant decrease in patients treated with solifenacin 5 (-1.42; P = 0.008) and 10 mg (-1.45; P = 0.0038). Compared with placebo (-1.20, -8.1%) the mean number of voids/24 h was significantly lower in patients receiving tolterodine (-1.88, -15%; P = 0.0145), solifenacin 5 (-2.19, -17%) and 10 mg (-2.61, -20%; both P < 0.001). The mean volume voided/void was also significantly higher with all three active treatments (P < 0.001). Solifenacin was well tolerated; compared with placebo (4.9%), dry mouth (the most common side-effect), mostly mild, was reported in 18.6% of patients receiving tolterodine, 14.0% receiving 5 mg and 21.3% receiving 10 mg solifenacin. CONCLUSION: Solifenacin 5 and 10 mg once daily improved urgency and other symptoms of OAB, and was associated with an acceptable level of anticholinergic side-effects. Solifenacin demonstrated significantly favourable efficacy to side-effect ratio in treating symptomatic OAB.     

Efficacy and safety of onabotulinumtoxinA injection in patients with refractory overactive bladder: First multicentric study in Turkish population

Aims

To investigate the efficacy and safety of intradetrusor onabotulinumtoxinA (onaBoNT‐A) injection in patients with overactive bladder (OAB) refractory to antimuscarinic treatment.

Methods

A total of 80 patients with OAB symptoms were enrolled in this prospective multicenter study and received 100 U intradetrusor onaBoNT‐A injection.The changes from baseline in the frequency of voiding, urge urinary incontinence (UI) and urge episodes, mean and maximum bladder capacities, uroflowmetry, post‐void residual urine volume (PVR), quality of life score, and treatment benefit scale score were assessed. The need for a second injection,and treatment‐related adverse events were also examined postoperatively.

Results

OnaBoNT‐A injection significantly decreased the UI episodes(P = 0.0001), the mean voiding frequency (P = 0.0001), and the urgency episodes (P = 0.0001) in the third month compared to baseline. Similarly, the mean bladder capacity, and maximal bladder capacity were increased (P < 0,05). The quality of life scores improved by 57.1% compared to the pre‐treatment rate (P = 0,0001). No significant change was observed in the PVR or maximum flow rate. Urinary retention developed in 3 (3.75%) patients and urinary infection and transient hematuria were observed in five patients (6.25%) each. The UI episodes, voiding frequency and urgency episodes were significantly lower at the 9th month than at baseline (all P = 0.0001). Overall 67% of the patients continued to experience benefits from the injection. Sixteen patients (20%) required a second injection in the third month. Eight patients were lost to follow‐up at the last visit in the 9th month, and 34 of the remaining 56 patients required a second injection at the 9th month. Cumulatively, 50 (63%) patients needed re‐injections.

Conclusions

Our results demonstrated that the onaBoNT‐A injection produced significant improvement in all OAB symptoms with a low incidence of treatment related adverse events.     

Symptom change in women with overactive bladder after extracorporeal magnetic stimulation: a prospective trial

The purpose of this study was to prospectively evaluate symptom change after discontinuation of extracorporeal magnetic stimulation (EMS) in women with overactive bladder (OAB). A total of 48 women with OAB were included. We applied 10 Hz of repetitive magnetic stimulation with a “magnetic chair” for 20 min, twice weekly for 8 weeks. Changes in OAB symptoms at 2, 12, and 24 weeks after discontinuing the EMS were evaluated. Twenty-seven (56.3%) patients were cured compared with the baseline at 2 weeks: the cure rate was determined as 68.8% (33/48 patients), 56.3% (27/48), and 50% (8/16) for urgency, frequency, and urge incontinence, respectively. The mean number of voids per 24 h was decreased by 42.8% (from 14.5 ± 4.3, to 8.3 ± 1.5, P < 0.001) at 2 weeks after treatment. Maximum voided volume did not change significantly, but the mean voided volume increased significantly after stimulation. Twenty-six (96.3%) patients among the 27 patients who achieved a cure at 2 weeks, maintained improvement at 24 weeks; the therapeutic effect on urgency, frequency, and urge incontinence persisted in 26 (78.8%) of 33 patients, 26 (96.3%) of 27 patients, and six (75%) of eight patients, respectively. There were no significant changes in urodynamic parameters. Of the 14 patients with detrusor overactivity, the condition was no longer observed in four (28.6%) patients. EMS has a beneficial effect on women with OAB. Our data suggest EMS may have a significant carry-over effect in well-selected OAB patients.     

Urinary urgency outcomes after propiverine treatment for an overactive bladder: the ‘Propiverine study on overactive bladder including urgency data’

Study Type – Therapy (RCT)
Level of Evidence 1b

OBJECTIVE

To investigate the effects of a daily regimen of propiverine 20 mg in patients with an overactive bladder (OAB), focused on improving urgency, as the clinical efficacy of treatment for OAB should be measured in terms of urgency, the cornerstone symptom of OAB.

PATIENTS AND METHODS

Eligible patients aged ≥18 years with symptoms of OAB were enrolled in this multicentre, prospective, parallel, double‐blind, placebo‐controlled trial. Of 264 patients (mean age 52.2 years), 221 who had efficacy data available from baseline and at least one on‐treatment visit with >75% compliance with medication were analysed (142 in the propiverine group and 79 in the placebo group). All patients were randomized to receive a placebo or 20 mg propiverine once daily in a 12‐week study. They completed a 3‐day voiding diary before visits during the study period, including the severity of urgency associated with every voiding, using the Indevus Urgency Severity Scale and the Urgency Perception Score. The patients’ overall self‐evaluation of treatment benefits at the end of the study, and safety data, were also collected.

RESULTS

The daily urgency episodes reduced significantly from baseline to 12 weeks on propiverine treatment, compared with placebo (?46.0% vs ?31.3%, P = 0.005). Secondary endpoints, including sum of urgency severity per 24 h, urgency severity per void, and daytime voiding frequency, were also improved significantly in the propiverine group. Overall, of those patients treated with propiverine, 38.7% rated their treatment as providing ‘much benefit’, compared with 15.2% of the placebo group (P = 0.025). Adverse events reported by 32 (22.5%) and 10 (12.7%) patients in the propiverine and placebo group were all tolerable. However, this is a short‐term study using only one fixed regimen.

CONCLUSIONS

Propiverine 20 mg once‐daily could be an effective treatment for patients with OAB, by improving urgency.     

Early versus late treatment of voiding dysfunction with pelvic neuromodulation

Introduction:

Pelvic neuromodulation is an established method of treating voiding dysfunction. Little is known about the pathophysiology associated with voiding dysfunction. Reports have suggested that a delay in treating patients with sacral neuromodulation therapy can impact the success rate of this type of treatment in voiding dysfunction. We examined patient response to pelvic neuromodulation when it was applied early versus late in the postdiagnosis of voiding dysfunction.

Methods:

We conducted a retrospective study of 42 patients (38 women and 4 men) with voiding dysfunction who underwent surgery for implant with the Interstim (Medtronic, Minneapolis, Minn.). Prior to implantation, patients were required to pass a percutaneous nerve evaluation (PNE) over a 1-week period. Patients were observed for 20–48 months postimplantation. All patients recorded their voiding parameters at baseline, after screening and every 6 months thereafter. Twenty patients (in the early group) underwent implant surgery with the neurostimulator 2–4 weeks post-PNE, and 22 patients (the late group) had the device implanted 6–24 months post-PNE owing to local logistical circumstances.

Results:

In the early group, 16 of 20 patients (80%) maintained a good response. In the late group, 13 of 22 (59%) patients showed a good response. Groups were well matched in terms of age, duration of voiding dysfunction and incidence of comorbidity.

Conclusion:

Patients who were delayed more than 6 months in receiving the neurostimulator implant showed a worse response than did patients who had the device implanted soon after PNE. This indicates the possibility of disease progression, which may limit the response to sacral neuromodulation.Sacral neuromodulation (SNM), using permanent foramen S3 electrode, offers an alternative treatment for patients with conditions refractory to conventional measures. SNM has been approved by the US Food and Drug Administration for 3 indications: urge incontinence (UI), urge frequency (UF) and nonobstructive urinary retention. Several reports have been published regarding the efficacy of SNM in the treatment of UI, UF and nonobstructive urinary retention.^1–4SNM is considered a minimally invasive procedure, and when compared with the more drastic procedures to control intractable overactive bladder symptoms, SNM has fewer complications and has provided patients with more durable and consistent bladder control over time.The purpose of the current study is to determine whether a delay in SNM can affect the long-term outcome of treatment in patients with voiding dysfunction.     

The Role of Neuromodulation in Patients with Neurogenic Overactive Bladder

To review the treatment options for patients with neurogenic overactive bladder (OAB), specifically the use of sacral neuromodulation (SNM). A search was performed on the available literature on SNM and lower urinary tract dysfunction. Based on published studies available and also on personal experience, the treatment options for neurogenic OAB are reviewed, and specifically, the role for SNM in these patients is discussed. SNM is FDA-approved for patients with urge incontinence, urgency/frequency, and non-obstructive urinary retention. It involves stimulation of the third sacral nerve with an electrode implanted in the sacral foramen and connected to a pulse generator. The procedure is minimally invasive and is effective in about 70?% of patients who have a permanent system. The original trials leading to the approval of SNM excluded patients with neurogenic disease, as it was felt that intact spinal pathways were necessary for neuromodulation to occur. However, similar success rates have been observed in patients with neurogenic OAB. Special considerations for SNM use in patients with neurogenic OAB include recognizing that it is incompatible for patients who will need MRI's due to their progressive neurologic disease. Many treatment options are available for patients with neurogenic OAB. First-line approaches remain conservative with lifestyle changes and anticholinergic medications. SNM has been used successfully in this patient population with good results, though larger randomized trials are lacking.     

Efficacy,safety, and tolerability of mirabegron in patients aged ≥65 yr with overactive bladder wet: a phase IV,double-blind,randomised, placebo-controlled study (PILLAR)

BackgroundThe majority of patients with overactive bladder (OAB) are aged >65 yr. There has been no prospectively designed study assessing treatment efficacy with the β3-adrenoreceptor agonist, mirabegron, specifically in this age group.ObjectiveA phase IV study comparing flexibly dosed mirabegron versus placebo in elderly patients with OAB and urgency incontinence.Design, setting, and participantsCommunity-dwelling patients aged ≥65 yr with OAB for ≥3 mo.InterventionFollowing a 2-wk placebo run in, patients with one or more incontinence episodes, three or more urgency episodes, and an average of eight or more micturitions/24 h were randomised 1:1 to double-blind 25 mg/d mirabegron or matched placebo, for 12 wk. After week 4 or 8, the dose could be increased to 50 mg/d mirabegron/matched placebo based on patient and investigator discretion.Outcome measurements and statistical analysisCoprimary endpoints: change from baseline to end of treatment (EOT) in the mean numbers of micturitions/24 h and incontinence episodes/24 h. Secondary endpoints: change from baseline to EOT in the mean volume voided/micturition, mean number of urgency episodes/24 h, and mean number of urgency incontinence episodes/24 h. Analysis of covariance (ANCOVA) was used for the mean number of micturitions/24 h, mean volume voided/micturition, and mean number of urgency episodes/24 h. Stratified rank ANCOVA was used for the mean numbers of incontinence episodes/24 h and urgency incontinence episodes/24 h.Results and limitationsStatistically significant improvements were observed for mirabegron versus placebo in change from baseline to EOT in the mean number of micturitions/24 h, mean number of incontinence episodes/24 h, mean volume voided/micturition, mean number of urgency episodes/24 h, and mean number of urgency incontinence episodes/24 h. Safety and tolerability were consistent with the known mirabegron safety profile.ConclusionsMirabegron efficacy, safety, and tolerability over 12 wk were confirmed in patients aged ≥65 yr with OAB and incontinence.Patient summaryWe examined the effect of mirabegron compared with placebo in people aged 65 yr or older with overactive bladder and incontinence. Mirabegron improved the symptoms of overactive bladder compared with placebo. Side effects were similar to those already known for mirabegron.     

A pooled analysis of three phase III studies to investigate the efficacy, tolerability and safety of darifenacin, a muscarinic M3 selective receptor antagonist, in the treatment of overactive bladder

OBJECTIVE: To evaluate the efficacy, tolerability and safety of darifenacin, a muscarinic M3 selective receptor antagonist (M3 SRA), from an analysis of pooled data from three phase III, multicentre, double-blind clinical trials in patients with overactive bladder (OAB). PATIENTS AND METHODS: After a 4-week washout/run-in period, 1059 adults (85% women) with symptoms of OAB (frequency and urgency with urge incontinence) for > or = 6 months were randomized to once-daily oral treatment with darifenacin (7.5 mg, 337; or 15 mg, 334) or matching placebo (388) for 12 weeks. Efficacy was evaluated using electronic patient diaries that recorded incontinence episodes (including those resulting in a change of clothing or pads), frequency and severity of urgency, voiding frequency, and bladder capacity (volume voided). Safety was evaluated by analysis of adverse events (AEs), withdrawal rates and laboratory tests. RESULTS: Relative to baseline, 12 weeks of treatment with darifenacin resulted in a significant reduction in the median (% change, interquartile range) number of incontinence episodes per week; 7.5 mg (-8.8, -68.4%, -15.1 to -4.4); 15 mg; (-10.6, -76.8%, -17.3 to -5.8: both P < 0.01 vs placebo). There was a significant dose-response trend in each study for which darifenacin 7.5 and 15 mg were evaluated (P < 0.01). There were also significant decreases in the frequency and severity of urgency, voiding frequency, and number of significant leaks (incontinence episodes resulting in a change of clothing or pads; both P < or = 0.001 vs placebo), together with an increase in bladder capacity (both P < 0.01 vs placebo). Darifenacin was well tolerated; the most common AEs were dry mouth and constipation, although together these resulted in few discontinuations (darifenacin 7.5 mg 0.6% of patients; 15 mg 2.1%; placebo 0.3%). The incidence of peripheral/central nervous system and cardiovascular AEs were comparable with those on placebo. CONCLUSIONS: Darifenacin (7.5 and 15 mg once daily) is effective in the treatment of patients with OAB. As predicted by its M3 selectivity and associated M1/M2-sparing profile, darifenacin was well tolerated with no central nervous system or cardiovascular safety concerns.     

Preliminary experience and possible predictors of successful mirabegron treatment for overactive bladder

ObjectiveThe aim of this study was to report our preliminary experience of the treatment with mirabegron and to identify the predictors of a successful treatment with mirabegron in overactive bladder (OAB) patients.Materials and methodsBetween October 2015 and February 2016, 234 consecutive patients (167 men and 67 women; mean age: 65.6 years; standard deviation: 16.3) diagnosed with OAB and receiving mirabegron monotherapy were enrolled retrospectively. Four weeks after mirabegron treatment, a global response assessment (GRA) was performed for all patients and analyses were performed to identify possible predictors of successful mirabegron treatment (defined as GRA ≥ 1). Mirabegron was intended being given for at least 12 weeks. Adverse events (AEs) and reasons for discontinuing mirabegron were recorded between 4 and 12 weeks of following-up.ResultsThe rate of successful mirabegron treatment (GRA ≥ 1) was 70.5%. The proportion of patients with a successful response was significantly higher in men than in women (75.3% vs. 60.5%, p = 0.022). The success rates as well as the percentage of older patients between groups with or without diabetes, hypertension, nocturia, urge incontinence, or prior anticholinergic treatment were not significantly different. Multivariable analysis showed that male sex was a significant independent predictor (p < 0.05) for successful treatment. The overall rate of AEs was 3.8%, including five cases with hypertension (2.1%) and three with severe voiding difficulty (1.3%). A total of 136 patients (58%) were administered mirabegron for more than 12 weeks. The reasons for discontinuing mirabegron included symptom improvement (17%), loss to follow-up (13%), poor treatment efficacy (8%), and side effects (4%).ConclusionsThe success rate of mirabegron treatment for OAB patients was high and the rate of overall AEs was low. Although only 58% patients continued mirabegron at 12 weeks, most patients (17%) discontinued the treatment because of reduction in symptoms. Male sex showed better response to mirabegron treatment.     

Time to onset of improvement in symptoms of overactive bladder using antimuscarinic treatment

OBJECTIVE: To evaluate the time to onset of statistically significant and clinically meaningful effects of trospium chloride in patients with an overactive bladder (OAB). PATIENTS AND METHODS: Data from a recent Phase III clinical study of trospium chloride were obtained, in which 658 patients with OAB were randomized (1 : 1) to placebo or trospium chloride 20 mg twice daily for 12 weeks. Original study safety endpoints consisting of adverse events, vital signs, electrocardiograms, and laboratory changes were collected, while original efficacy endpoints included number of toilet voids/day, urgency severity per toilet void, urge urinary incontinence (UUI), and volume voided per toilet void at weeks 1, 4, and 12. Results were also analysed using the OAB Symptom Composite Score (OAB-SCS). The efficacy analysis focused on changes from baseline in these endpoints from 1 to 7 days of treatment to establish the earliest point at which there was statistical significance or clinical efficacy. RESULTS: There were statistically significant improvements in efficacy over placebo in endpoints (toilet voids, urgency severity/void, UUI episodes, OAB-SCS) within a few days of treatment, with improvements in symptoms continuing to 7 days of treatment. There were clinically meaningful improvements in most endpoints by the end of the first week. CONCLUSIONS: The time to onset of the clinical effect should be studied more extensively to identify when patients might expect a clinically meaningful improvement in their OAB-related symptoms.     

Extended-release tolterodine with or without tamsulosin in men with lower urinary tract symptoms and overactive bladder: effects on urinary symptoms assessed by the International Prostate Symptom Score

OBJECTIVE

To evaluate the efficacy of tolterodine extended‐release (ER) plus tamsulosin on lower urinary tract symptoms (LUTS) as assessed by changes in the International Prostate Symptom Score (IPSS) in men who met symptom entry criteria for both overactive bladder (OAB) and benign prostatic hyperplasia (BPH) trials.

PATIENTS AND METHODS

Men aged ≥40 years with an IPSS of ≥12 and diary‐documented OAB symptoms (≥8 voids/24 h and ≥3 urgency episodes/24 h, with or without urgency urinary incontinence) who reported at least moderate problems related to their bladder condition were randomized to receive placebo, tolterodine ER (4 mg), tamsulosin (0.4 mg), or tolterodine ER (4 mg) + tamsulosin (0.4 mg) once daily for 12 weeks. Patients completed the IPSS at baseline and at 1, 6 and 12 weeks.

RESULTS

Patients receiving tolterodine ER + tamsulosin had significantly greater improvements than those taking placebo on IPSS storage subscale scores and scores for all three individual storage items included on the IPSS (urinary frequency, urgency, and nocturnal micturitions) by 12 weeks. Storage subscale and urgency scores were significantly improved vs placebo at 1 and 6 weeks, whereas frequency scores were significantly improved at 6 weeks. Changes in IPSS storage subscale and individual storage item scores in the tolterodine ER and tamsulosin monotherapy groups were not significantly different from placebo at most time points. IPSS voiding subscale scores and scores for three of four individual voiding items (sensation of incomplete emptying, intermittency, and weak stream) were significantly improved by 12 weeks for patients receiving tamsulosin monotherapy vs placebo. Voiding subscale and intermittency scores were significantly improved vs placebo at 1 week; weak stream scores were significantly improved at 1 and 6 weeks. The IPSS voiding subscale and individual voiding item scores in the tolterodine ER + tamsulosin and tolterodine ER groups were not significantly different from placebo at most time points.

CONCLUSIONS

In this distinct clinical research population of men who met traditional symptom entry criteria for both OAB and BPH trials, tolterodine ER + tamsulosin was significantly more effective than placebo in treating storage LUTS, including OAB symptoms. Tamsulosin monotherapy produced significant improvements in voiding LUTS.     

The current and future burden and cost of overactive bladder in five European countries

OBJECTIVE: To estimate and compare the current and future direct cost of overactive bladder (OAB) to the health care systems of five European countries. METHOD: A health economic model was created to estimate the number of people currently affected by OAB symptoms, the expected number to be affected in the future, and the resultant economic burden on health care systems in Germany, Italy, Spain, Sweden, and the United Kingdom. RESULTS: The model estimated that in 2000, 20.2 million people over age 40 in the five countries experienced the symptoms of OAB; 7 million of these had urgency with urge incontinence. This figure is expected to rise to 25.5 million by 2020, including 9 million who will have urgency with urge incontinence. Average annual direct costs of OAB management ranged from euro269 to euro706 per patient per year. The largest cost was the use of incontinence pads, accounting for an average of 63% of the annual per patient cost of OAB management. Total cost to health care systems across all five countries was estimated at euro4.2 billion in 2000, and by 2020, the expected total cost was estimated to be euro5.2 billion, an increase of euro1 billion (26%). CONCLUSION: OAB is prevalent, with a substantial direct cost that is anticipated to increase in the future in line with aging populations. The overall burden, including indirect costs, may be considerably larger, and will fall predominantly on the elderly OAB population with urge incontinence. Recommended medical treatments could help manage those costs and should be evaluated.