The impact of overactive bladder on mental health, work productivity and health-related quality of life in the UK and Sweden: results from EpiLUTS

Study Type – Symptom prevalence (prospective cohort) Level of Evidence 1b

OBJECTIVE

? To examine the prevalence and burden of overactive bladder (OAB) with bother in the UK and Sweden compared to OAB without bother and no/minimal OAB/lower urinary tract (LUTS) symptoms, respectively.

PATIENTS AND METHODS

? A cross‐sectional population‐representative survey was conducted via the Internet in the UK, Sweden and USA. ? Participants rated the frequency and bother of OAB and LUTS. Patient outcomes included the Overactive Bladder Questionnaire Short Form, Patient Perception of Bladder Condition, Short Form‐12, Hospital Anxiety and Depression Scale–Anxiety and Hospital Anxiety and Depression Scale–Depression, as well as questions about treatment seeking and work productivity. ? OAB was defined as urgency at least sometimes or the presence of urinary urgency incontinence. Three subgroups were compared: no/minimal symptoms, OAB without bother and OAB with bother. ? Analyses were conducted by gender and country using general linear and logistic regression models to examine bothersome OAB and treatment seeking.

RESULTS

? Survey response was 59.2%; 10 000 people (4724 men and 5276 women) participated. ? The prevalence of OAB with bother at least ‘somewhat’ was 10.9% and 14.6% for men in the UK and Sweden, and 22.5% and 33.7% for women in the UK and Sweden, respectively. ? Men and women with bothersome OAB were significantly more likely to seek treatment, report the lowest levels of health‐related quality of life and work productivity and the highest levels of anxiety and depression compared to those with no/minimal symptoms and OAB without bother. ? Greater symptom severity of urgency, urgency urinary incontinence, frequency, nocturia, and increasing levels of anxiety were strongly predictive of OAB bother in both men and women. ? Predictors of treatment seeking included frequency, bother as a result of urgency, and lower levels of depressive symptoms in men, and frequency, nocturia and urgency in women.

CONCLUSIONS

? OAB is common in the UK and Sweden, and women are more likely to be affected then men. ? The impact of OAB is evident across generic and condition‐specific domains of health‐related quality of life.     

Overactive bladder symptoms after midurethral sling surgery in women: Risk factors and management

Introduction

Overactive bladder syndrome (OAB) including urgency and urgency urinary incontinence (UUI) occurs frequently after stress urinary incontinence (SUI) surgery. It is important to identify the risk factors for the occurrence of OAB symptoms in order to adequately inform the patient before surgery. Furthermore, when facing OAB after sling surgery it is crucial to know how to manage these symptoms.

Methods

We conducted a literature review in order to assess the risk factors and management of OAB symptoms after SUI surgery. We searched for relevant articles in PubMed that specifically addressed the topic of OAB symptoms after midurethral sling surgery.

Results

The incidence of de novo and persistent urgency and UUI is reported around 15% and 30%, respectively. Several studies demonstrated that women with mixed incontinence who have a predominant urge component will have worse outcomes after surgery. Older age was also found to be a predictive factor in three studies. Furthermore, urodynamic signs of overactive bladder (eg, DO, low bladder capacity, elevated detrusor pressure) can predict postoperative urgency or UUI. The management of OAB symptoms after SUI surgery is essentially the same as in idiopathic OAB. However, before commencing therapy it is crucial to rule out other factors than can cause urgency, including bladder outlet obstruction, urinary tract infection, or sling erosion.

Conclusions

OAB symptoms are frequently reported after sling surgery. Women with mixed incontinence and older women are at risk of developing post‐operative OAB symptoms. We have proposed an algorithm for the treatment of these symptoms which can be useful in clinical practice.     

Prevalence and predictors of overactive bladder in nonpregnant nulliparous women below 65 years of age

Introduction and hypothesis

The aetiology of the overactive bladder (OAB) symptom complex is still poorly understood. In order to obtain further insight, the prevalence and predictors of the symptoms included in OAB, that is urgency, urgency incontinence (UUI), frequency and nocturia, were investigated in a sample of nonpregnant nulliparous women.

Methods

A national, postal and web-based survey of OAB symptoms was conducted in women aged 25–64 years (n = 9,197). Crude prevalence and prevalence adjusted according to body mass index (BMI) were calculated from a logistic regression model to evaluate the prevalence of OAB.

Results

The response rate was 52%. The prevalence of urgency, bothersome urgency, UUI, and nocturia, but not daytime frequency, increased consistently with advancing age and increasing BMI. Urgency was associated with BMI, age ≥45 years, nocturia, and daytime frequency of eight or more micturitions. Daytime urinary micturition frequency was not affected by age either in women with OAB or in women without OAB. Bothersome OAB affected almost half of the woman in the oldest age group and was strongly associated with nocturia of two or more micturitions and OAB with UUI.

Conclusions

There were contrasting changes in the prevalence of the different symptoms included in OAB. With increasing age and BMI, the prevalence of nocturia, urgency and UUI increased, while daytime frequency remained stable. These findings are of importance as the primary endpoint for the evaluation of drug therapies for OAB has often been daytime urinary frequency.

     

Association of overactive bladder and C-reactive protein levels. Results from the Boston Area Community Health (BACH) Survey

Study Type – Aetiology (cohort) Level of Evidence 3a What's known on the subject? and What does the study add? Evidence of chronic inflammation in benign prostatic hyperplasia suggests a role of inflammation in the development of lower urinary tract symptoms. However, few studies have investigated the association of inflammation and overactive bladder in both men and women. Results of this population‐based study show a consistent association of increased C‐reactive protein levels with overactive bladder in both men and women. These results support the hypothesized role of inflammation in the development of overactive bladder.

OBJECTIVE

• ? To investigate the association between overactive bladder (OAB) and C‐reactive protein (CRP) in a population‐based sample of men and women.

SUBJECTS AND METHODS

• ? Epidemiological survey of urological symptoms among men and women aged 30–79 years. A multi‐stage stratified cluster design was used to randomly sample 5503 adults from the city of Boston. Analyses were conducted on 1898 men and 1854 women with available CRP levels.
• ? The International Continence Society defines OAB as ‘Urgency with or without urge incontinence, usually with frequency and nocturia.’ OAB was defined as: (1) urgency, (2) urgency with frequency, and (3) urgency with frequency and nocturia.
• ? Odds ratios (OR) and 95% confidence intervals (95% CI) of the CRP and OAB association were estimated using logistic regression.

RESULTS

• ? Prevalence of OAB increased with CRP levels in both men and women.
• ? In men, adjusted ORs (95% CI) per log₁₀(CRP) levels were 1.90 (1.26–2.86) with OAB defined as urgency, 1.65 (1.06–2.58) with OAB defined as urgency and frequency, and 1.92 (1.13–3.28) with OAB defined as urgency, frequency and nocturia.
• ? The association was more modest in women with ORs (95% CI) of 1.53 (1.07–2.18) for OAB as defined urgency, 1.51 (1.02–2.23) for OAB defined as urgency and frequency, and 1.34 (0.85–2.12) for OAB defined as urgency, frequency and nocturia.

CONCLUSIONS

• ? Results show a consistent association of increasing CRP levels and OAB among both men and women.
• ? These results support our hypothesis for the role of inflammation in the development of OAB and a possible role for anti‐inflammatory agents in its treatment.

     

Solifenacin in the treatment of urgency and other symptoms of overactive bladder: results from a randomized, double-blind, placebo-controlled, rising-dose trial

OBJECTIVES

To examine the effects of the antimuscarinic agent solifenacin on urinary urgency, using a range of novel and established outcome measures, as urgency is the principal symptom of the overactive bladder syndrome (OAB).

PATIENTS AND METHODS

The study (SUNRISE, solifenacin in the treatment of urgency symptoms of OAB in a rising dose, randomized, placebo‐controlled, double‐blind, efficacy trial) was a randomized, double‐blind, 16‐week, placebo‐controlled, multicentre study of solifenacin 5/10 mg in 863 patients with symptoms of OAB for ≥3 months. The primary efficacy variable was the change from baseline to endpoint in the number of episodes of severe urgency with or without urgency incontinence per 24 h, as measured using the Patient Perception of Intensity of Urgency Scale, grade 3 + 4. Secondary efficacy variables included patient‐reported outcomes for bladder condition, urgency bother and treatment satisfaction. A 3‐day voiding diary was used to record micturition frequency and episodes of urgency and incontinence. A 7‐day diary was used to assess speed of onset of effect.

RESULTS

Solifenacin 5/10 mg was significantly more effective than placebo in reducing the mean number of episodes of severe urgency with or without incontinence per 24 h from baseline to endpoint (?2.6 vs ?1.8, P < 0.001). There were also statistically significant differences in favour of solifenacin 5/10 mg over placebo for all secondary variables measured at endpoint, including patient‐reported outcomes. There was a significant improvement in urgency as early as day 3 of treatment. Treatment‐emergent adverse events with solifenacin 5/10 mg were mainly mild or moderate in severity, and only led to discontinuation in 3.6% of patients.

CONCLUSION

Solifenacin significantly reduced the number of urgency episodes and the extent of urgency bother, and was well tolerated; it was effective as early as day 3 of treatment.     

Severe depression and anxiety in women with overactive bladder

Aim

Depression and anxiety are prevalent psychiatric conditions and are associated with overactive bladder. The objective of this study was to determine prevalence and severity of anxiety and depression associated with overactive bladder (OAB) in women.

Methods

274 women with clinical diagnosis of OAB were recruited from 2012 to 2015. They were submitted to the International Consultation on Incontinence Questionnaire‐Overactive Bladder (ICIQ‐OAB), the Beck Depression Inventory (BDI), and the Beck Anxiety Inventory (BAI).

Results

Severe or moderate depression was present in 59.8% of women and severe or moderate anxiety was identified in 62.4%. Higher scores of depression and anxiety were associated with higher scores of ICIQ‐OAB (P = 0.0031 and 0.0049). Women with severe depression had higher nocturia score than those with mild depression (P = 0.0046). Also, women with severe depression had higher urgency incontinence score than those with minimal depression (P = 0.0261). Patients with severe anxiety had higher nocturia score than those with minimal anxiety (P = 0.0118) and women with moderate anxiety had higher urgency incontinence score than with minimal anxiety (P = 0.0300).

Conclusions

Moderate or severe depression and anxiety are prevalent in women with OAB. There is a correlation between intensity of OAB symptoms with depression and anxiety. Anxiety and depression levels are mainly related with urgency incontinence and nocturia.     

Associations between subjective overactive bladder symptoms and objective parameters on bladder diary and filling cystometry

Introduction and hypothesis

A study was conducted to assess associations between different overactive bladder (OAB) symptoms and their outcomes on bladder diary and filling cystometry parameters.

Methods

We performed a retrospective cohort study in database of 6,876 Urinary Distress Inventories, 3,185 bladder diaries and 2,153 filling cystometries from women referred to our urogynecological center between 2003 and 2009. Women were dichotomized into two groups. Group I: those women without symptoms, and those with symptoms that were not bothersome. Group II: women with bothersome symptoms. Data obtained from bladder diaries were: daytime urinary frequency, nocturnal frequency, minimum voided volume, maximum voided volume, average voided volume, and incontinence episodes. From filling cystometries, volumes at first desire to void, normal desire to void, strong desire to void and maximum cystometric capacity, were extracted. Univariate and multiple linear regression analysis were performed to determine associations between OAB symptoms and bladder diary and filling cystometry measurements.

Results

After multivariate analysis the objective daytime frequency was most strongly associated with the frequency symptom (β 0.27, p?<?0.05), night time frequency with the nocturia symptom (β 0.40, p?<?0.05) and the number of incontinence episodes with the urge incontinence symptom (β 0.37, p?<?0.05). Both frequency and nocturia symptoms were significantly associated with bladder diary and cystometry filling volumes, and their effect size was the same. The urgency symptom proved to be poorly associated with objective parameters.

Conclusions

In contrast to the frequency and nocturia symptom, the urgency symptom is poorly associated with objective parameters on bladder diary and filling cystometry. Therefore, the current practice of using frequency and incontinence episodes in outcome research of OAB trials is justified.     

Overactive bladder in diabetes mellitus patients: a questionnaire-based observational investigation

Purpose

Bladder dysfunction, secondary to diabetes, is mainly characterized by poor bladder emptying and overflow incontinence. However, there is evidence in literature that storage symptoms, as those suggestive for overactive bladder (OAB), may also affect people with diabetes. The aim of this study was to evaluate the prevalence of overactive bladder, the complaint of urinary urgency with/without urge incontinence, usually with frequency and nocturia, in people with diabetes compared to healthy subjects (control group).

Methods

Symptoms were assessed through the overactive bladder questionnaire (OAB-q), an investigative tool, specifically developed for OAB diagnosis.

Results

OAB-q scores resulted higher in diabetic people than those of the control group. Age and disease duration resulted in measurements that showed a statistical correlation with the OAB-q scores.

Conclusions

OAB symptoms are more prevalent in diabetic people than in non-diabetic people. This prompts further research to determine whether the onset of OAB symptoms can be considered as an indicator of diabetic neuropathy.     

Assessment of overactive bladder symptoms among women with successful pessary placement

Introduction and hypothesis

The causal association between pelvic organ prolapse (POP) and overactive bladder (OAB) symptoms is supported by several theories. The aim of this study is to assess any changes in OAB symptoms among women with POP and OAB after successful pessary placement.

Methods

During the study period, all women with symptomatic POP stage II or greater and OAB symptoms were offered the solution of either a ring or a Gellhorn pessary. All patients were asked to complete a 3-day micturition/incontinence diary. Objective evaluation endpoints at baseline and at 6 weeks included: change in the mean number of micturitions/24 h, change in the mean volume voided per micturition/24 h, and change in the number of urinary incontinence episodes. Subjective evaluation of the urgency, frequency, and nocturia symptoms was carried out using the score change of the questions 3, 5, and 2 of the International Consultation on Incontinence Questionnaire for Evaluating Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) respectively.

Results

Seventy-four women were included in the study. A statistically significant decrease (?28.3%; p < 0.001) of the mean number of micturitions/24 h with a significant increase (37%; p < 0.001) in the mean voided volume per micturition/24 h was observed. The total urine volume/24 h remained unchanged. The number of urinary incontinence episodes was significantly increased 6 weeks after pessary placement (p < 0.001). De novo stress urinary incontinence (SUI) was reported by 16.7% of the initially stress continent women.

Conclusions

Women with coexisting POP and OAB symptoms may experience a significant improvement in micturition frequency and in urgency and frequency symptoms after successful pessary fitting.

     

Understanding the elements of overactive bladder: questions raised by the EPIC study

OBJECTIVES

To compare the prevalence of frequency and nocturia and the bother they impose in a population‐based sample of men and women using current International Continence Society (ICS) definitions of lower urinary tract symptoms (LUTS) and commonly used alternative definitions of these LUTS to emphasize the importance of standardizing the definitions when evaluating overactive bladder (OAB) syndrome; we also describe the spectrum of LUTS and bother they impose in this population with OAB.

SUBJECTS AND METHODS

Several validated disease‐specific measures were used in a population‐based, cross‐sectional telephone survey of adults aged ≥18 years in five countries. The population with OAB was defined as those participants who answered ‘yes’ to questions about urgency or urgency urinary incontinence according to ICS standards. The prevalence of daytime frequency and nocturia within the OAB population was examined using two different criteria for each symptom. Frequency was defined using the current ICS definition (i.e. subject’s perception of whether they urinated too often during the day) or more than eight daytime voids. Nocturia was defined according to the ICS definition of having to wake once or more per night to void and using the threshold of waking twice or more per night to urinate. Urinary symptom bother within the OAB population was compared using the different criteria for frequency and nocturia.

RESULTS

In all, 1434 participants (502 men and 932 women) were classified as having OAB; 31% of men and 25% of women with OAB had daytime frequency consistent with the ICS definition. The ICS‐defined frequency identified a population with a varied distribution of reported daytime voiding frequencies; most respondents reported frequencies below the threshold of nine daytime voids. The ICS‐defined daytime frequency was reported as bothersome by more than half of the OAB population (46% of men, 66% of women). Of the OAB population, ≈75% reported one or more nocturia episodes per night, and ≈40% reported two or more per night. The proportion of the OAB population that was bothered by nocturia increased markedly as the number of nocturia episodes increased. Among those with OAB, the most prevalent combination of OAB symptoms was urgency and nocturia. More than half of those with OAB reported urgency combined with three or more other LUTS (including voiding and postmicturition symptoms), and the number of LUTS reported increased with age. The proportion of the population reporting symptom bother increased as the number of reported LUTS in that population increased.

CONCLUSIONS

The ICS definitions for daytime frequency as ‘the subject’s perception of urinating too often’ and for nocturia as ‘one or more episodes per night’ adequately described bladder symptoms within the OAB population when assessed by the level of symptom bother. Urgency was uncommon in isolation and did not alone impose as high a level of bother as when combined with other LUTS. In this population, the most predominant manifestation of OAB was a combination of urgency with one or more other OAB symptoms. Symptom bother became more common as the number of symptoms reported increased. LUTS other than the defining symptoms of OAB were also highly prevalent within the OAB population.     

Outcome of coexistent overactive bladder symptoms in women with urodynamic urinary incontinence following anti-incontinence surgery

Introduction and hypothesis

The objective was to investigate the outcome of stress urinary incontinence (SUI) and overactive bladder (OAB) symptoms in women with urodynamic stress incontinence (USI) after transobturator sling procedures (TOTs).

Methods

We evaluated 109 consecutive patients with USI, who had undergone TOT in a tertiary hospital between 2012 and 2014. All patients received evaluations, including structured urogynecological questionnaires and pelvic organ prolapse quantification examination before, and 3 and 12 months after surgery. One-hour pad test and urodynamic testing were performed before and 3–6 months postoperatively. Patient demographics, lower urinary tract symptoms, and urodynamic results were analyzed between pure USI and USI with OAB symptoms.

Results

Persistent SUI occurred in 8 patients at 3 months (7.3 %) and 7 patients at 12 months (6.4 %) postoperatively. The most common OAB symptom was frequency (54.1 %), followed by urgency urinary incontinence (52.3 %), urinary urgency (42.2 %), and nocturia (33 %). Most of these OAB symptoms were resolved at the 3-month and 12-month follow-ups both in patients treated with TOT only and in those treated with TOT combined with other pelvic surgeries. There was no significant difference in the preoperative urodynamic changes between patients with pure USI and USI without OAB groups. However, postoperative urodynamic results showed a significant decrease in the maximal urethral closure pressure in the group of patients with USI and OAB symptoms, but no significant urodynamic changes in the group with pure USI.

Conclusions

Coexistent OAB symptoms are common in women who were diagnosed with USI and most of these symptoms may resolve 3 and 12 months after TOT.

     

THE COST‐EFFECTIVENESS OF SOLIFENACIN VS FESOTERODINE,OXYBUTYNIN IMMEDIATE‐RELEASE,PROPIVERINE, TOLTERODINE EXTENDED‐RELEASE AND TOLTERODINE IMMEDIATE‐RELEASE IN THE TREATMENT OF PATIENTS WITH OVERACTIVE BLADDER IN THE UK NATIONAL HEALTH SERVICE

OBJECTIVE

Please also see BJUI letters on page 586 To assess the cost‐effectiveness of solifenacin vs other antimuscarinic strategies commonly used in UK clinical practice, based on the results of a recent published review.

METHODS

Overactive bladder (OAB) syndrome is characterized by symptoms of urgency, frequency, incontinence and nocturia. Pharmacological treatment comprises oral antimuscarinic agents, which are divided into older‐generation treatments, including oxybutynin, and new‐generation treatments, comprising solifenacin, tolterodine, darifenacin and fesoterodine. The latter have reduced central nervous system penetration and have better selectivity for the M3 subclass of acetylcholine receptors, resulting in improved tolerability. A recent systematic review and meta‐analysis of the efficacy and safety of antimuscarinics provided an opportunity for an economic evaluation of these agents using a rigorous assessment of efficacy. A cost‐utility analysis was undertaken using a 1‐year decision‐tree model. Treatment success was defined separately for urgency, frequency and incontinence, with efficacy data taken from the recent review. Treatment persistence rates were taken from the Information Management System database. Utility values for the calculation of quality‐adjusted life‐years (QALYs) were taken from published sources. The analysis included costs directly associated with treatment for OAB, i.e. antimuscarinic therapy, consultations with general practitioners, and outpatient contacts. Resource use was based on expert opinion. Costs were reported at 2007/2008 prices. Extensive deterministic and probabilistic analyses were conducted to test the robustness of the base‐case results.

RESULTS

Solifenacin was associated with the highest QALY gains (per 1000 patients) for all three outcomes of interest, i.e. urgency (712.3), frequency (723.1) and incontinence (695.0). Solifenacin was dominant relative to fesoterodine, tolterodine extended‐release (ER) and tolterodine immediate‐release (IR), and cost‐effective relative to propiverine ER for urgency, frequency and incontinence. Solifenacin was not found to be cost‐effective relative to oxybutynin IR for the frequency and incontinence outcomes, with an incremental cost‐effectiveness ratio of >£30 000/QALY threshold.

CONCLUSIONS

Solifenacin provided the greatest clinical benefit and associated QALYs for all three outcomes of interest across all therapies considered, and to be either dominant or cost‐effective relative to all other new‐generation agents, but not cost‐effective relative to oxybutynin for frequency and incontinence.     

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.     

The prevalence of detrusor overactivity amongst patients with symptoms of overactive bladder: a retrospective cohort study

Introduction and hypothesis

Overactive bladder (OAB) is a symptom-based condition consisting of urgency, with or without incontinence, usually with frequency and nocturia. There are many potential causes of OAB, yet many patients are prescribed anticholinergic medications empirically. This study aimed to determine what proportion of patients presenting for urogynecologic assessment with symptoms of OAB had urodynamic detrusor overactivity (DO).

Methods

Retrospective chart review was performed for 220 consecutive patient referrals. Demographic data, physical exam information, and urodynamic results were collected. The t test and Fisher’s exact test were used for statistical analyses.

Results

The prevalence of DO was 11.8?% in this population. Urogenital atrophy and incomplete emptying were more common. Patients with DO were older and more often menopausal than those without DO. Significant prolapse was a common finding amongst patients with OAB symptoms.

Conclusions

Patients with symptoms of OAB should undergo pelvic examination and assessment of post-void residuals before being initiated on anticholinergic medication.     

Vibegron,a Novel Potent and Selective β3-Adrenoreceptor Agonist,for the Treatment of Patients with Overactive Bladder: A Randomized,Double-blind,Placebo-controlled Phase 3 Study

Background

Vibegron is a novel, potent, and selective β₃-adrenoreceptor agonist for the treatment of patients with overactive bladder (OAB).

How should patients with an overactive bladder manipulate their fluid intake?

OBJECTIVE

To assess how the symptoms of overactive bladder (OAB) syndrome in adults are affected by decreasing or increasing fluid input, and the effect of fluid manipulation on quality of life.

PATIENTS AND METHODS

Adults with symptoms of OAB were randomized in a two‐group, prospective, cross‐over trial following a 4‐day screening period (to establish baseline values) using frequency/volume charts, if they had a mean of eight or more voids and one or more urgency and/or urgency incontinence episodes in 24‐h. Patients were asked to either increase or decrease their fluid intake, from baseline, as follows: group 1, 4 days drinking 25% less than baseline, and 2 days normal, then 4 days at 50% less than baseline, and 2 days normal, then 4 days at 25% more than baseline, and 2 days normal, and then 4 days at 50% more than baseline. Group 2 did the reverse. The primary endpoint was the change in the frequency of unwanted events during a 24‐h period.

RESULTS

In all, 67 patients were contacted, 40 recruited and 24 were eligible. There was a significant reduction in frequency, urgency and nocturia when patients decreased their fluid input by 25%. Increasing fluid input by 25% and 50% resulted in a worsening of daytime frequency. Overall there was no statistically significant improvement in quality of life but there was some subjective improvement in urgency and nocturia, as measured by a validated instrument, in the group that decreased their fluid input by 25%; ≈300 mL of daily fluid came from water‐containing foods.

CONCLUSIONS

Fluid manipulation is a cheap, noninvasive and easy way to help control the symptoms of OAB. Patients have difficulty in either decreasing or increasing their fluid input by 50%. Patients can now be told to expect a significant improvement in urgency, frequency and nocturia episodes if they reduce their fluid input by 25%.     

Is mirabegron equally as effective when used as first- or second-line therapy in women with overactive bladder?

Introduction and hypothesis

No previous studies have investigated the efficacy of mirabegron 50 mg as the first-line therapy in OAB patients. Hence, the primary objective of this study was to evaluate the efficacy of mirabegron in treatment-naive patients in comparison with those who had discontinued antimuscarinic therapy because of insufficient efficacy.

Methods

All consecutive women who had pure OAB symptoms (including urgency with or without urgency incontinence and frequency) for at least 3 months were considered for this study. Women were divided into two groups: women without any previous pharmacological treatment for OAB (group 1) and women with a previous history of failed antimuscarinics therapy (group 2).

Results

At 3-month follow-up, the objective results on the basis of the frequency–volume chart showed a significant improvement in both groups. Furthermore, a significant reduction in the Overactive Bladder Questionnaire Short Form (OABq-SF) score and in the Indevus Urgency Severity Scale (IUSS) questionnaire were reported in both groups. However, the improvement in objective and subjective outcomes was superior in group 1 to that in group 2.

Conclusions

Mirabegron is efficacious in improving OAB symptoms in both naïve patients and those who discontinued primary antimuscarinic therapy; however, its efficacy is superior when prescribed as first-line therapy.

     

Does BMI,gender or age affect efficacy/tolerability of solifenacin in the management of overactive bladder?

Introduction and Hypothesis

Pooled data from seven randomized placebo-controlled trials were analysed to evaluate relationships between baseline body mass index (BMI), gender or age and the efficacy/tolerability of solifenacin (5 – 10 mg daily) in patients with overactive bladder (OAB).

Methods

Changes in efficacy variables from baseline to 12 weeks were compared in patients with symptoms at baseline between solifenacin-treated and placebo-treated groups. Normalization rates were calculated (no more than eight micturitions in 24 h, no more than one episode of nocturia per night, zero values for other variables over 24 h). Treatment-emergent adverse events (TEAEs) were recorded.

Results

The baseline incidence of incontinence and urgency incontinence increased with increasing BMI and age; relatively more women than men were incontinent. The baseline incidence of urgency was similar between genders and among age groups, but tended to increase with increasing BMI. The baseline frequencies of micturition and nocturia were similar in all BMI categories, between genders and in all age groups. The results from this meta-analysis of an integrated database of data from trials investigating solifenacin showed that solifenacin was more efficacious than placebo for all OAB symptoms across all BMI and age categories, and between genders. Normalization rates for micturition frequency, incontinence and urgency were greater in patients receiving solifenacin than in those receiving placebo across all categories. The overall incidence of TEAEs was higher in patients receiving solifenacin than in those receiving placebo; solifenacin was generally well tolerated in both groups. The overall frequency of TEAEs for solifenacin and placebo was slightly higher in women than in men and in older than in younger patients. The most commonly reported TEAEs were dry mouth and constipation.

Conclusions

Regardless of BMI, gender or age, all patients with OAB can be considered candidates for solifenacin treatment.

     

Ist der validierte ICIQ-SF zur Evaluation bei OAB-Patientinnen geeignet?

Background

The following data analysis studied the aspects of patient satisfaction following onabotulinum toxin A (BTX-A) treatment including modification of certain parameters, such as frequency of micturition and the use of pads and in particular, the applicability of the international consultation on incontinence questionnaire short form (ICIQ-SF) and the urgency perception scale (UPS) in patients with an overactive bladder (OAB).

Patients and method

In this study 40 female patients were questioned in the form of validated questionnaires (extended ICIQ-SF and UPS) before and after being injected with 300 IU of BTX-A in each detrusor muscle. The average age of the patients was 66 years. All patients experienced anticholinergic refractory, non-neurogenic OAB.

Results

The recommendation rate and related patient satisfaction was 82.5?%. A significant decrease in the frequency of micturition by 50.9?% (p?<?0.01) was reported as well as a significant reduction in the use of pads by 66.7?% (p?<?0.01). The average number of ICIQ-SF points could be significantly (p?<?0.01) reduced via BTX-A from 15.9 to 7.3. Moreover, BTX-A demonstrated a significant improvement in the urgency to urinate, which was illustrated through the UPS.

Conclusion

Treatment with BTX-A achieves significant improvements in female patients with anticholinergic refractory OAB with regard to the individual symptoms of OAB (e.g. pollakisuria, nocturia, undesired urination and urgency). The use of the ICIQ-SF as the only questionnaire in OAB diagnostics proved to be unsuitable as it does not include female patients with dry OAB to an adequate degree. A combination of various validated questionnaires, such as ICIQ-SF and UPS, proved to be useful.