Jameel Nazir

Comparative efficacy and safety of medical treatments for the management of overactive bladder: a systematic literature review and mixed treatment comparison.

CONTEXT Overactive bladder (OAB) treatment guidelines recommend antimuscarinics as first-line pharmacologic therapy. Mirabegron is a first-in-class β3-adrenoceptor agonist licensed for the treatment of OAB and has shown to be well tolerated and effective in the treatment of OAB symptoms. OBJECTIVE To assess the relative efficacy and tolerability of OAB medications, specifically mirabegron 50 mg versus antimuscarinics in patients with OAB. EVIDENCE ACQUISITION A systematic literature search was performed on published peer-reviewed articles from 2000 to 2013. This review included randomised controlled trials (RCTs) studying changes in symptoms (micturition frequency, incontinence, and urgency urinary incontinence [UUI] episodes) and incidence of the most frequently reported adverse events (dry mouth, constipation) associated with current OAB medications. The following drugs were considered in addition to mirabegron: darifenacin, tolterodine immediate release (IR) and extended release (ER), oxybutynin IR/ER, trospium, solifenacin, and fesoterodine. Bayesian mixed treatment comparisons (MTCs) were performed for efficacy (micturition, incontinence, UUI) and tolerability (dry mouth, constipation, blurred vision). EVIDENCE SYNTHESIS Overall, 44 RCTs involving 27,309 patients were included. The MTCs showed that mirabegron 50 mg was as efficacious as antimuscarinics in reducing the frequency of micturition incontinence and UUI episodes, with the exception of solifenacin 10 mg that was more efficacious than mirabegron 50 mg in improving micturition frequency and frequency of UUI. Mirabegron 50 mg had an incidence of dry mouth similar to placebo and significantly lower than all included antimuscarinics. CONCLUSIONS Mirabegron 50 mg had similar efficacy to most antimuscarinics and lower incidence of dry mouth, the most common adverse event reported with antimuscarinics and one of the main causes of discontinuation of treatment. Despite being a powerful tool for evidence-based health care evaluation, the Bayesian MTC method has limitations. Further head-to-head comparisons between mirabegron and antimuscarinics should be conducted to confirm our results.

Persistence and Adherence with Mirabegron versus Antimuscarinic Agents in Patients with Overactive Bladder: A Retrospective Observational Study in UK Clinical Practice

BACKGROUND Persistence with antimuscarinic therapy in overactive bladder (OAB) is poor, but may be different for mirabegron, a β3-adrenoceptor agonist with a different adverse event profile. OBJECTIVE To compare persistence and adherence with mirabegron versus tolterodine extended release (ER) and other antimuscarinics in routine clinical practice over a 12-mo period. DESIGN, SETTING, AND PARTICIPANTS Retrospective, longitudinal, observational study of anonymised data from the UK Clinical Practice Research Datalink GOLD database. Eligibility: age ≥18 yr, ≥1 prescription for target OAB drug (between May 1, 2013 and June 29, 2014), and 12-mo continuous enrolment before and after the index prescription date. INTERVENTIONS Mirabegron, darifenacin, fesoterodine, flavoxate, oxybutynin ER or immediate-release (IR), propiverine, solifenacin, tolterodine ER or IR, and trospium chloride. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary endpoint was persistence (time to discontinuation). Secondary endpoints included 12-mo persistence rates and adherence (assessed using medication possession ratio, MPR). Cox proportional-hazards regression models and logistic regression models adjusted for potential confounding factors were used to compare cohorts. Analyses were repeated after 1:1 matching. RESULTS AND LIMITATIONS The study population included 21996 eligible patients. In the unmatched analysis, the median time-to-discontinuation was significantly longer for mirabegron (169 d, interquartile range [IQR] 41-not reached) compared to tolterodine ER (56 d, IQR 28-254; adjusted hazard ratio [HR] 1.55, 95% confidence interval 1.41-1.71; p<0.0001) and other antimuscarinics (range 30-78 d; adjusted HR range 1.24-2.26, p<0.0001 for all comparisons). The 12-mo persistence rates and MPR were also significantly greater with mirabegron than with all the antimuscarinics. Limitations include the retrospective design, use of prescription records to estimate outcomes, and inability to capture reasons for discontinuation. CONCLUSIONS Persistence and adherence were statistically significantly greater with mirabegron than with tolterodine ER and other antimuscarinics prescribed for OAB in the UK. PATIENT SUMMARY This study assessed persistence and adherence (or compliance) with medications prescribed for OAB in a large UK population. We found that patients prescribed mirabegron remained on treatment for longer and showed greater adherence than those prescribed traditional antimuscarinics.

Economic and clinical contributions of an antimicrobial barrier dressing: a strategy for the reduction of surgical site infections

Abstract Objective: In patients at risk of surgical site infection (SSI), there is evidence that an antimicrobial barrier dressing (Acticoat) applied immediately post-procedure is effective in reducing the incidence of infection. The objective of this study was to assess when it is appropriate to use an antimicrobial barrier dressing rather than a post-operative film dressing, by evaluating the net cost and budget impact of the two strategies. Methods: An economic model was developed, which estimates expected expenditure on dressings and the expected costs of surgical site infection during the initial inpatient episode, based on published literature on the pre-discharge costs of surgical infection and the efficacy of an antimicrobial barrier dressing in preventing SSI. Results: At an SSI risk of 10%, an antimicrobial barrier dressing strategy is cost neutral if the incidence of infection is reduced by at least 9% compared with a post-operative film dressing. At 35% efficacy, expenditure on dressings would be higher by £30,760 per 1000 patients, and the cost of treating infection would be lower by £111,650, resulting in a net cost saving of £80,890. The break-even infection risk for cost neutrality is 2.6%. Limitations: Although this cost analysis is based on published data, there are limitations in methodology: the model is dependent on and subject to the limitations of the data used to populate it. Further studies would be useful to increase the robustness of the conclusions, particularly in a broader range of surgical specialities. Conclusions: A strategy involving the use of an antimicrobial barrier dressing in patients at moderate (5–10%) or high (>10%) risk of infection appears reasonable and cost saving in light of the available clinical evidence.

Estimating EQ-5D and OAB-5D health state utilities for patients with overactive bladder

BackgroundLimited utility data on patients suffering from overactive bladder (OAB) are available in the literature. The objectives of this study were to estimate utility values in patients with OAB using the generic EQ-5D questionnaire and the OAB-5D disease specific questionnaire, to investigate the relationship between utilities and symptoms, and to evaluate the sensitivity of the two instruments to changes in symptom severity.MethodsAnalyses were based on pooled data from three large multicenter randomized 12-week placebo-controlled trials (SCORPIO, ARIES, CAPRICORN). Patients completed a micturition diary, EQ-5D and OAB-q (a quality of life questionnaire from which OAB-5D is derived) at baseline and at weeks 4, 8 and 12. Time trade-off tariffs elicited from UK population were applied to obtain utilities from both instruments. Repeated measures regressions were used to estimate EQ-5D and OAB-5D utilities by micturition frequency and incontinence severity level. As a test of sensitivity of the instruments, utility changes from baseline to week 12 were estimated by symptomatic response (improvement, stable or worsening).ResultsThe sample included 4427 patients. Mean utilities (± standard deviation) across all visits were 0.82 (±0.21) for EQ-5D and 0.86 (±0.09) for OAB-5D. Correlation between EQ-5D and OAB-5D was 0.34 (p < 0.0001). Both OAB-5D and EQ-5D utilities increased as OAB symptoms improved. Utility values were similar for severe levels of symptoms, but higher with OAB-5D than with EQ-5D for mild cases. Micturitions and incontinence had similar impact on EQ-5D utilities, but micturitions had greater impact on OAB-5D utilities than incontinence. Changes from baseline in OAB-5D utilities differed significantly according to symptomatic response. Changes in EQ-5D utilities were not significantly associated with changes in micturition frequency and weakly associated with changes in incontinence severity among patients with mild symptoms at baseline.ConclusionsThis study showed that both EQ-5D and OAB-5D can detect changes in severity of OAB, especially in severe cases. However, OAB-5D is more sensitive than EQ-5D in measuring differences between treatments in milder cases. Both OAB-5D and EQ-5D–although leading to different results–may be useful to derive utilities from clinical trial data and perform cost-effectiveness analyses.Trial registrationClinical Trials NCT00689104, NCT00662909, NCT00912964.

Cost-Effectiveness of Mirabegron Compared with Antimuscarinic Agents for the Treatment of Adults with Overactive Bladder in the United Kingdom

BACKGROUND Mirabegron, a first-in-class selective oral β3-adrenoceptor agonist, has similar efficacy to most antimuscarinic agents and a lower incidence of dry mouth in patients with overactive bladder (OAB). OBJECTIVES To evaluate the cost-effectiveness of mirabegron 50 mg compared with oral antimuscarinic agents in adults with OAB from a UK National Health Service perspective. METHODS A Markov model including health states for symptom severity, treatment status, and adverse events was developed. Cycle length was 1 month, and the time horizon was 5 years. Antimuscarinic comparators were tolterodine extended release, solifenacin, fesoterodine, oxybutynin extended release and immediate release (IR), darifenacin, and trospium chloride modified release. Transition probabilities for symptom severity levels and adverse events were estimated from a mirabegron trial and a mixed treatment comparison. Estimates for other inputs were obtained from published literature or expert opinion. Quality-adjusted life-years (QALYs) and total health care costs, including costs of drug acquisition, physician visits, incontinence pad use, and botox injections, were modeled. Deterministic and probabilistic sensitivity analyses were performed. RESULTS Base-case incremental cost-effectiveness ratios ranged from £367 (vs. solifenacin 10 mg) to £15,593 (vs. oxybutynin IR 10 mg) per QALY gained. Probabilistic sensitivity analyses showed that at a willingness-to-pay threshold of £20,000/QALY gained, the probability of mirabegron 50 mg being cost-effective ranged from 70.2% versus oxybutynin IR 10 mg to 97.8% versus darifenacin 15 mg. A limitation of our analysis is the uncertainty due to the lack of direct comparisons of mirabegron with other agents; a mixed treatment comparison using rigorous methodology provided the data for the analysis, but the studies involved showed heterogeneity. CONCLUSIONS Mirabegron 50 mg appears to be cost-effective compared with standard oral antimuscarinic agents for the treatment of adults with OAB from a UK National Health Service perspective.

Patient-reported outcomes with the β3-adrenoceptor agonist mirabegron in a phase III trial in patients with overactive bladder

To assess patient‐reported outcomes (PROs) in patients with overactive bladder (OAB) receiving the novel β3‐adrenoceptor agonist mirabegron.

Drug treatment patterns for the management of men with lower urinary tract symptoms associated with benign prostatic hyperplasia who have both storage and voiding symptoms: a study using the health improvement network UK primary care data

Abstract Background: Real-world data on the pharmacological management of men who have lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) are limited. Objective: To characterize men with LUTS/BPH who had both storage and voiding symptoms and to evaluate treatment patterns in UK primary care. Design, setting and participants: This was an observational study of men aged ≥45 years with a diagnosis, symptoms or therapies indicative of LUTS/BPH with both storage and voiding components. These men were identified from the large Health Improvement Network (THIN) database between 1 January 2004 and 30 September 2011. Outcome measurements and statistical analysis: Drug prescriptions and switching/discontinuation patterns for α1-blockers and antimuscarinics. Results and limitations: We identified 8694 men with a median age of 66.0 (interquartile range [IQR], 59.0–74.0) years. Most (7850; 90.3%) received an α1-blocker, and 2167 (24.9%) received antimuscarinic therapy over a median of 2.1 years. The most commonly prescribed α1-blocker was tamsulosin (81.8%); most frequent antimuscarinics were tolterodine (41.0%), oxybutynin (37.2%) and solifenacin (35.7%). Concomitant prescription of α1-blocker and antimuscarinic therapy (within 30 days of each other) was received by 1160 men (14.8% of α1-blocker-treated men). Of α1-blocker recipients, 3024 (38.5%) discontinued during follow-up, while 1149 (53.0%) discontinued antimuscarinic therapy. Of 2167 men who received an antimuscarinic, 476 (22.0%) switched to another antimuscarinic. Of the three most commonly prescribed antimuscarinics, solifenacin had the lowest proportions of discontinuations (43.0%) and switches (15.3%), and the longest median duration of therapy (90 days, IQR 30–300). General practice consultations accounted for most resource use (5307.9 per 1000 patient-years). Conclusions: This study presents real-world management of men with LUTS/BPH who have both storage and voiding symptoms. The low proportion of men who received concomitant α1-blocker and antimuscarinic therapy suggests that some patients are sub-optimally treated in routine clinical practice.

Economic evaluation of pharmacological treatments for overactive bladder from the perspective of the UK National Health Service

Abstract Objective: To evaluate the costs and outcomes associated with different sequences of oral anti-muscarinic agents and the selective β3-adrenoceptor agonist, mirabegron, for the treatment of overactive bladder (OAB). Methods: A Markov model with monthly cycle length and time horizon up to 3 years was designed to compare two different sequences of up to three lines of oral therapy for OAB. Patients who discontinued one oral medication could switch to another oral medication or could discontinue treatment. Patients whose symptoms were not controlled were considered for botulinum toxin or sacral nerve stimulation. Outcomes were measured by (a) number of patients with controlled symptoms (no incontinence episodes and <8 micturitions per 24 h); (b) patients with no incontinence episodes per 24 hours; and (c) patients with <8 micturitions per 24 h. Results: Including a third-line oral medication before considering other treatment options improved all patient outcomes, irrespective of the specific drugs used. A three-line sequence including two generic (oxybutynin first line and tolterodine extended-release second line) and one branded drug (solifenacin 5 mg third line) resulted in inferior patient outcomes at costs similar to a sequence of branded drugs (mirabegron first line, solifenacin 5 mg second line, solifenacin 10 mg third line): controlled patients (generic 29.6/1000 vs branded 38.7/1000); patients with no incontinence episodes (103.6/1000 vs 123.7/1000); patients with <8 micturitions (228.7/1000 vs 262.1/1000). Annual treatment costs per patient were similar (generic £1299 vs branded £1385). Conclusions: In the treatment of OAB, low-cost generic treatments are not necessarily more cost-effective than branded drugs, primarily because a better efficacy and tolerability balance improves both symptom control and persistence.

Persistence and adherence with mirabegron vs antimuscarinics in overactive bladder: Retrospective analysis of a UK General Practice prescription database

Persistence with antimuscarinic (AM) drugs prescribed for overactive bladder (OAB) is poor. This study aimed to compare persistence and adherence with the beta‐3‐adrenoceptor agonist mirabegron (MIR) vs AMs over 12 months.

Responder and health-related quality of life analyses in men with lower urinary tract symptoms treated with a fixed-dose combination of solifenacin and tamsulosin oral- controlled absorption system: results from the NEPTUNE study

To evaluate the effect of a fixed‐dose combination (FDC) of solifenacin and an oral‐controlled absorption system (OCAS™) formulation of tamsulosin (TOCAS) on health‐related quality of life (HRQoL) in men with lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH).