Dataset Information

Adverse event assessment of antimuscarinics for treating overactive bladder: a network meta-analytic approach.

ABSTRACT:

Background

Overactive bladder (OAB) affects the lives of millions of people worldwide and antimuscarinics are the pharmacological treatment of choice. Meta-analyses of all currently used antimuscarinics for treating OAB found similar efficacy, making the choice dependent on their adverse event profiles. However, conventional meta-analyses often fail to quantify and compare adverse events across different drugs, dosages, formulations, and routes of administration. In addition, the assessment of the broad variety of adverse events is dissatisfying. Our aim was to compare adverse events of antimuscarinics using a network meta-analytic approach that overcomes shortcomings of conventional analyses.

Methods

Cochrane Incontinence Group Specialized Trials Register, previous systematic reviews, conference abstracts, book chapters, and reference lists of relevant articles were searched. Eligible studies included randomized controlled trials comparing at least one antimuscarinic for treating OAB with placebo or with another antimuscarinic, and adverse events as outcome measures. Two authors independently extracted data. A network meta-analytic approach was applied allowing for joint assessment of all adverse events of all currently used antimuscarinics while fully maintaining randomization.

Results

69 trials enrolling 26'229 patients were included. Similar overall adverse event profiles were found for darifenacin, fesoterodine, transdermal oxybutynin, propiverine, solifenacin, tolterodine, and trospium chloride but not for oxybutynin orally administered when currently used starting dosages were compared.

Conclusions

The proposed generally applicable transparent network meta-analytic approach summarizes adverse events in an easy to grasp way allowing straightforward benchmarking of antimuscarinics for treating OAB in clinical practice. Most currently used antimuscarinics seem to be equivalent first choice drugs to start the treatment of OAB except for oral oxybutynin dosages of ? 10 mg/d which may have more unfavorable adverse event profiles.

SUBMITTER: Kessler TM

PROVIDER: S-EPMC3044140 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Publications

Adverse event assessment of antimuscarinics for treating overactive bladder: a network meta-analytic approach.

Kessler Thomas M TM Bachmann Lucas M LM Minder Christoph C Löhrer David D Umbehr Martin M Schünemann Holger J HJ Kessels Alfons G H AG

PloS one 20110223 2

<h4>Background</h4>Overactive bladder (OAB) affects the lives of millions of people worldwide and antimuscarinics are the pharmacological treatment of choice. Meta-analyses of all currently used antimuscarinics for treating OAB found similar efficacy, making the choice dependent on their adverse event profiles. However, conventional meta-analyses often fail to quantify and compare adverse events across different drugs, dosages, formulations, and routes of administration. In addition, the assessm ...[more]

PMID: 21373193

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Project description:IntroductionThis study aimed to assess overactive bladder (OAB) treatment patterns and factors associated with effectiveness and persistence.MethodsA prospective, longitudinal, observational registry study of adults starting OAB therapy with mirabegron or antimuscarinics was undertaken. Primary endpoints were time from treatment initiation to discontinuation/switching; proportion who discontinued/switched; and reasons for discontinuation/switching. Secondary endpoints included OAB Symptom Score (OABSS), OAB Questionnaire: Short Form, and OAB Bladder Assessment Tool scores; factors associated with effectiveness and persistence; and safety.ResultsIn total, 556 patients initiating mirabegron and 250 initiating antimuscarinics were enrolled. There was no treatment switch, change, or discontinuation in 68.5% of the mirabegron initiator group and median time to treatment change was not reached. Mean initial treatment duration was 130.8 days. In multivariable models, baseline OABSS was the only variable significantly associated with change from baseline in OABSS, and patients with mild and moderate OAB had significantly better persistence with mirabegron than those with severe OAB. Urinary tract infection was the most common adverse event with mirabegron. There was no treatment switch, change, or discontinuation in 60.4% of the antimuscarinics initiator group and median time to treatment change was not reached. Solifenacin was the most frequent initial treatment (66.0%). Mean treatment duration was 122.2 days. In multivariable models, baseline OABSS was the only variable significantly associated with change from baseline in OABSS, while patients with OAB medication in the 12 months before enrollment had significantly better persistence with antimuscarinics than those with no previous OAB medication. Dry mouth was the most common adverse event with antimuscarinics.ConclusionsMirabegron and solifenacin were commonly prescribed as first-line OAB medications. There was no treatment switch, change, or discontinuation in more than 60% of the mirabegron initiator and antimuscarinics initiator groups. Mean initial treatment duration was 130.8 days and 122.2 days for mirabegron and antimuscarinics, respectively. Graphical Abstract available for this article.Trial registrationClinicalTrials.gov NCT03572231.

Project description:BACKGROUND:Persistence on-treatment with antimuscarinics in patients with overactive bladder (OAB) is reported to be sub-optimal. This retrospective, longitudinal, observational cohort study assessed treatment persistence with ?3-adrenoceptor agonists (i.e. mirabegron) and antimuscarinics, both classes of OAB pharmacotherapy, in patients with OAB in Spain. METHODS:Adults who received mirabegron or an antimuscarinic in routine clinical practice (1 June-31 October 2014), were identified from anonymised prescription data within the Spanish Cegedim Electronic Medical Records database. The primary endpoint, treatment persistence (time to treatment discontinuation [TTD] and the proportion of patients remaining on-treatment after 12 months), was unadjusted for potential confounders. Multivariate Cox regression models of persistence, adjusted for baseline characteristics, were used to compare differences in treatment groups. Adjusted subgroup analyses (target OAB drug, age, treatment status and sex) and sensitivity analyses (extending the time used to define treatment discontinuation from 30 days [base-case] to 45, 60 or 90 days without prescription renewal) were also performed. RESULTS:Overall, 1798 patients received mirabegron (N =?1169) or an antimuscarinic (N =?629); the mean age was 66.42 years. Median TTD was longer for mirabegron versus antimuscarinics (90 vs 56 days) and a higher proportion of patients who received mirabegron were persistent after 12 months (20.2% vs 10.2%); multivariate analyses indicated significantly greater persistence with mirabegron versus antimuscarinics (hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.37-1.70; p <?0.001). Significant differences were also observed in subgroup analyses of mirabegron versus individual antimuscarinics (median TTD: 90 vs [range] 28-60 days; HR range: 1.21-2.17; p ??0.013) and in all other subgroups assessed (p <?0.001). Sensitivity analysis showed that the median TTD for mirabegron increased by up to 31 days, and was significantly longer versus antimuscarinics across all adjusted periods (HR range: 1.43-1.53; all p <?0.001). CONCLUSIONS:Patients with OAB in Spain who received mirabegron experienced longer persistence on-treatment than those who received antimuscarinics and the proportion of patients persistent on-treatment at 12 months with mirabegron was two-times higher versus antimuscarinics. These data may provide strategic insights for clinicians and policy makers involved in the management of OAB.

Project description:BackgroundWhile overactive bladder is often managed in the primary care setting, a number of barriers including embarrassment, poor communication, and low patient adherence contribute to the under-treatment of patients with burdensome urinary symptoms. In order to address these challenges, it is crucial to have a fundamental understanding of patient perspectives toward OAB and urinary symptoms. To meet this aim, researchers designed and conducted a study to identify patients' knowledge, experiences and attitudes, barriers to treatment adherence, and desires and tendencies regarding patient/clinician communications.MethodsA mixed-methods qualitative/quantitative needs assessment of patients with overactive bladder and/or urinary symptoms. Researchers conducted in-depth qualitative interviews via telephone with 40 patients. Interview results informed the design and dissemination of a quantitative survey, which was completed by 200 self-selected respondents who had previously identified themselves as having overactive bladder or bladder problems. Statistical and qualitative analysis of results were conducted.ResultsAmong survey respondents, an average of 3.5 years elapsed between symptom onset and seeking diagnosis by a physician. In the long term most patients do not experience improvement in symptoms. Medication non-adherence is common and is related to therapy effectiveness and adverse effects. Patients clearly indicate that communication and patient/physician relationships are important to them and they would prefer the clinician initiate the conversation on overactive bladder. Patient experiences, perspectives, and attitudes toward their bladder symptoms differ in many ways from clinicians' assumptions.ConclusionsThe significant time gap between symptom onset and diagnosis indicates ongoing need for screening and diagnosis of overactive bladder. Contrary to guideline recommendations, urinalysis and physical examination are not widely used in clinical practice. Many patients experience no improvement in symptoms over time. Patients indicate that clinician/patient relationships and communication regarding their condition are important.

Project description:OnabotulinumtoxinA and mirabegron have recently gained marketing authorisation to treat symptoms of overactive bladder (OAB).To evaluate the relative efficacy of mirabegron and onabotulinumtoxinA in patients with idiopathic OAB.Network meta-analysis.A search of 9 electronic databases, review documents, guidelines and websites.Randomised trials comparing any licensed dose of onabotulinumtoxinA or mirabegron with each other, anticholinergic drugs or placebo were eligible (19 randomised trials were identified). 1 reviewer extracted data from the studies and a second reviewer checked the data. Candidate trials were assessed for similarity and networks were developed for each outcome. Bayesian network meta-analysis was conducted using both fixed-effects and random-effects models. When there were differences in mean baseline values between mirabegron and onabotulinumtoxinA trials they were adjusted for using network meta-regression (NMR).No studies directly comparing onabotulinumtoxinA to mirabegron were identified. A network was created for each of the 7 outcomes, with 3-9 studies included in each individual network. The trials included in the networks were broadly similar. Patients in the onabotulinumtoxinA trials had more urinary incontinence and urgency episodes at baseline than patients in the mirabegron trials and these differences were adjusted for using NMR. Both onabotulinumtoxinA and mirabegron were more efficacious than placebo at reducing the frequency of urinary incontinence, urgency, urination and nocturia. OnabotulinumtoxinA was more efficacious than mirabegron (50 and 25 mg) in completely resolving daily episodes of urinary incontinence and urgency and in reducing the frequency of urinary incontinence, urgency and urination. NMR supported the results of the network meta-analysis.In the absence of head-to-head trials comparing onabotulinumtoxinA to mirabegron, this indirect comparison indicates that onabotulinumtoxinA may be superior to mirabegron in improving symptoms of urinary incontinence, urgency and urinary frequency in patients with idiopathic OAB.

Dataset Information

Adverse event assessment of antimuscarinics for treating overactive bladder: a network meta-analytic approach.

Background

Methods

Results

Conclusions

Publications

Adverse event assessment of antimuscarinics for treating overactive bladder: a network meta-analytic approach.

Similar Datasets

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