Use Of Mirabegron Research Articles

An individual participant meta-analysis of mirabegron in multiple sclerosis and spinal cord injury.

Our objective was to conduct an individual patient data meta-analysis (IPDMA) of the two published randomized placebo-controlled trials of mirabegron in people with neurogenic lower urinary tract dysfunction (NLUTD) due to spinal cord injury (SCI) or multiple sclerosis (MS). We identified two randomized, placebo-controlled trials. We extracted individual patient data from the trials and evaluated two primary outcomes: change in maximum cystometric capacity and change in the patient perception of bladder condition (PPBC). We also evaluated several secondary outcomes related to urodynamic function and quality of life. We conducted three exploratory analyses to test hypotheses based on our clinical experiences with mirabegron in NLUTD. Analysis of covariance with adjustment for baseline values was used for the statistical analysis. Our IPDMA included 98 patients from the two trials. The results showed that mirabegron was associated with a significant improvement in maximum cystometric capacity (+41 mL, p = 0.04) and in the PPBC (-0.8, p < 0.01) compared to placebo. Secondary outcomes including peak neurogenic detrusor overactivity pressure (-20 cm H2O, p < 0.01), incontinence-QOL score (+12, p < 0.01), and 24 h pad weights (-79 g, p = 0.04) also improved significantly compared to placebo. Exploratory analyses found similar improvements in people with MS and SCI; some outcomes improved to a greater degree among people with incomplete SCI,or SCIs that were below T7. Our IPDMA provides evidence supporting the use of mirabegron in patients with NLUTD due to SCI or MS. Further work evaluating differential responses in people with different SCI lesion characteristics may be warranted.

Cost analysis for mirabegron use in the treatment of children with neurogenic bladder

Mirabegron is a beta-3 adrenergic receptor agonist that received FDA approval in 2021 to treat neurogenic detrusor overactivity (NDO) in children ages three years and older. Despite its safety and efficacy, access to mirabegron frequently remains restricted by payor coverage policies. This cost minimization study sought to determine the cost implications from a payor perspective of mirabegron use at different points in the treatment pathway for pediatric NDO. A Markov decision analytic model was constructed to assess the costs for eight treatment strategies over a 10-year period, using six-month cycles (Table). Five strategies involve mirabegron use as first-, second-, third-, or fourth-line therapy. Two strategies, including the "base case," entail use of anticholinergic medications followed by onabotulinum toxin type A (Botox) injection and augmentation cystoplasty. A strategy involving first-line Botox was also modeled. The effectiveness, adverse event rates, attrition rates, and costs associated with each treatment option were obtained from the clinical literature and adjusted to a six-month cycle. Costs were adjusted to 2021-dollar value. A discount rate of 3% was used. To quantify uncertainty, costs and treatment transition probabilities were modeled as gamma and PERT distributions, respectively. One-way sensitivity analyses were performed. Probabilistic sensitivity analysis (PSA) was conducted using a Monte Carlo simulation with 100,000 iterations. Analyses were performed using Treeage Pro (Healthcare Version). The least costly strategy involved first-line mirabegron (expected cost $37,954). All strategies involving mirabegron were less costly than the base case ($56,417). On PSA, first-line mirabegron was the least costly strategy in 88.9% of cases (mean $37,604, 95% CI: $37,579-37,628); in 100% of cases, the least costly strategy involved mirabegron use. Cost savings associated with mirabegron use were attributable to decreased use of augmentation cystoplasty and Botox injections. This is the first study to compare costs across multiple strategies involving mirabegron to treat pediatric NDO. Mirabegron use likely yields cost savings for the payor: the least costly strategy involved first-line mirabegron, and all pathways incorporating mirabegron were less costly than those without mirabegron use. These findings provide an updated cost analysis for the treatment of NDO by investigating mirabegron use alongside more established treatment options. Use of mirabegron for the treatment of pediatric NDO is likely associated with cost savings as compared to treatment pathways without mirabegron. Expansion of payor coverage for mirabegron, as well as clinical studies to study first-line mirabegron use, should be considered.

Mirabegron and Anticholinergics in the Treatment of Overactive Bladder Syndrome: A Meta-analysis.

To compare the use of mirabegron with anticholinergics drugs for the treatment of overactive bladder (OB). Systematic searches were conducted in EMBASE, PUBMED, Cochrane, and LILACS databases from inception to September 2021. We included RCTs, women with clinically proven OB symptoms, studies that compared mirabegron to antimuscarinic drugs, and that evaluated the efficacy, safety or adherence. RevMan 5.4 was used to combine results across studies. We derived risk ratios (RRs) and mean differences with 95% CIs using a random-effects meta-analytic model. Cochrane Collaboration Tool and GRADE was applied for risk of bias and quality of the evidence. We included 14 studies with a total of 10,774 patients. Fewer total adverse events was reported in mirabegron group than in antimuscarinics group [RR 0.93 (0.89-0.98)]. The risk of gastrointestinal tract disorders and dry mouth were lower with mirabegron [RR 0,58 (0.48-0.68); 9375 patients; RR 0.44 (0.35-0.56), 9375 patients, respectively]. No difference was reported between mirabegron and antimuscarinics drugs for efficacy. The adherence to treatment was 87.7% in both groups [RR 0.99 (0.98-1.00)]. Mirabegron and antimuscarinics have comparable efficacy and adherence rates; however, mirabegron showed fewer total and isolated adverse events.

Assessment of Codispensing Patterns of Mirabegron and Prespecified CYP2D6 Substrates in Patients with Overactive Bladder.

Patients with overactive bladder (OAB) experience sudden, intense urges to urinate, which may include urge urinary incontinence and nocturia. Pharmacotherapy includes β3-adrenergic receptor agonists such as mirabegron; however, mirabegron contains a label warning for cytochrome P450 (CYP) 2D6 inhibition, making coadministration with CYP2D6 substrates require monitoring and dose adjustment to avoid unintended increases in substrate concentration. To understand the codispensing patterns of mirabegron among patients using ten predefined CYP2D6 substrates with and before mirabegron dispensing. This retrospective claims database analysis used the IQVIA PharMetrics® Plus Database to assess codispensing of mirabegron with ten predefined CYP2D6 substrate groups identified on the basis of medications most frequently prescribed in the UnitedStates, those with high susceptibility to CYP2D6 inhibition, and those with evidence for exposure-related toxicity. Patients had to be ≥18 years old before initiation of the CYP2D6 substrate episode that overlapped with mirabegron. The cohort entry period was November 2012 to September 2019, and the overall study period was 1 January 2011 to 30 September 2019. Comparisons of patient profiles at dispensing were made between time periods with and before mirabegron use in the same patient. Descriptive statistics were used to assess the number of exposure episodes, total duration of exposure, and median duration of exposure of CYP2D6 substrate dispensing with and before mirabegron. CYP2D6 substrate exposure periods totaling ≥9000 person-months were available before overlapping exposure to mirabegron for all ten CYP2D6 substrate cohorts. Median codispensing duration for chronically administered CYP2D6 substrates was 62 (interquartile range [IQR] 91) days for citalopram/escitalopram, 71 (105) days for duloxetine/venlafaxine, and 75 (115) days for metoprolol/carvedilol; median codispensing duration for acutely administered CYP2D6 substrates was 15 (33) days for tramadol and 9 (18) days for hydrocodone. In this claims database analysis, the dispensing patterns of CYP2D6 substrates with mirabegron displayed frequent overlapping of exposure. Thus, a need exists to better understand the outcomes experienced by patients with OAB who are at increased risk for drug‒drug interactions when taking multiple CYP2D6 substrates concurrently with a CYP2D6 inhibitor.

Assessing Quality-of-Life of Patients Taking Mirabegron for Overactive Bladder.

Lower urinary tract symptoms (LUTS), including urgency, frequency, and urgency incontinence, are highly prevalent in the general population and increase in prevalence with increasing age. All LUTS, but notable urgency and urgency incontinence, are associated with negative impact on quality-of-life (QoL), with multiple aspects of QoL affected. Urgency and urgency incontinence are most commonly caused by overactive bladder (OAB), the clinical syndrome of urinary urgency, usually accompanied by increased daytime frequency and/or nocturia in the absence of infection or other obvious etiology, which may be treated with conservative and lifestyle interventions, bladder antimuscarinic drugs, and, more recently, by mirabegron, a β3 agonist. This narrative review describes the impact of OAB on QoL, quantifies this impact, and outlines the evidence for the use of mirabegron in the treatment of, and improvement in QoL in, people with OAB.

Mirabegron and antimuscarinic use in frail overactive bladder patients in the United States Medicare population.

Overactive bladder (OAB) and frailty are independently associated with patient burden. However, economic burden and treatment-taking behavior have not been well characterized among frail patients with OAB, which, given the varying safety and tolerability profiles of available treatments, is crucial. To assess costs, health care resource utilization, treatment-taking behavior (persistence and adherence) to OAB medication in older, frail OAB patients. This was a retrospective cohort study using international business machines MarketScan Medicare Supplemental claims data. Eligible frail patients (per Claims-based Frailty Index score) initiating mirabegron were 1:2 propensity score matched (based on age, sex, and other characteristics) with those initiating antimuscarinics and were followed up to 1 year. All-cause, per-person, per-month costs, health care encounters, persistence (median days to discontinuation assessed using Kaplan-Meier methods) and adherence (≥80% of proportion of days covered at Day 365) were compared. From 2527 patients with incident mirabegron (21%) or antimuscarinic (79%) dispensations, 516 incident mirabegron users (median age: 82 years, 64% female) were matched to 1032 incident antimuscarinic users (median age: 81 years, 62% female). Median cost was higher in mirabegron group ($1581 vs. $1197 per month); this was primarily driven by medication cost. There was no difference in medical encounters. Adherence (39.1% vs. 33.8%) and persistence (103 vs. 90 days) were higher in mirabegron users. Among frail older adults with OAB, mirabegron use was associated with higher costs and potential improvements in treatment-taking behaviors, particularly with respect to treatment adherence, versus those initiating antimuscarinics.

Mirabegron: pharmacoeconomic aspects of the use of the drug for the treatment of overactive bladder syndrome

According to the International Continence Society (ICS), symptoms of overactive bladder (OAB) are present in 17 % of the adult population of Europe. The prevalence of overactive bladder in Russia is unknown but is considered comparable to that in European countries. According to Russian guidelines, patients with OAB could be treated with antimuscarinics or beta 3-agonists. The results of a meta-analysis by Wang J et al. (2018) showed comparable efficacy and safety of mirabegron and solifenacin. At the same time, according to Chapple CR et al. (2017) and Yeowell G et al. (2018) the use of mirabegron is associated with greater adherence to therapy and longer average drug use before the need to change therapy compared to antimuscarinics. From an economic point of view, greater adherence to drug therapy is associated with lower costs per patient with OAB per year and mirabegron have demonstrated to be cost-eff ective in comparison to solifenacin. The results of the analysis of the structure and volume of providing various types of medical care to patients with OAB in the Moscow region demonstrate the need to expand approaches to providing drug care to this group of patients. Currently, the majority of costs related to patients with OAB are associated with surgical treatment, which indicates the opportunity to expand the possibilities of drug therapy, including within the framework of preferential drug provision.

Urological Management at Discharge from Acute Spinal Cord Injury Rehabilitation: A Descriptive Analysis from a Population-based Prospective Cohort

BackgroundThere is limited epidemiological evidence describing contemporary neuro-urological management of persons with acute spinal cord injury (SCI). ObjectiveTo describe neurogenic lower urinary tract dysfunction (NLUTD) management at discharge from SCI rehabilitation. Design, setting, and participantsThe population-based Swiss Spinal Cord Injury (SwiSCI) cohort study prospectively collected data from 602 adults undergoing specialized postacute SCI rehabilitation from 2013 to 2020. The management strategy was based on the European Association of Urology (EAU) Guidelines on Neuro-Urology. Outcome measurements and statistical analysisData were collected at discharge using the International SCI Lower Urinary Tract Function Basic Data Set. Multivariable logistic regression adjusting for demographics, SCI characteristics, and center, with inverse probability weighting accounting for sampling bias, was used to produce prevalence estimates and identify predictors of lower urinary tract symptoms (LUTS) and NLUTD management outcomes. Results and limitationsAt discharge (median time after SCI: 5.0 mo [Q1-Q3: 3.0–7.2]), the prevalence of LUTS or managed NLUTD was 82% (95% confidence interval [CI]: 79–85%). SCI completeness was the main predictor of LUTS and managed NLUTD. The risk of urinary incontinence was elevated in females (odds ratio 1.98 [95% CI: 1.18–3.32]) and with complete lesions (odds ratio 4.71 [95% CI: 2.52–8.81]). Voiding dysfunction was most commonly managed with intermittent catheterization (prevalence 39% [95% CI: 35–42%]), followed by indwelling catheterization (prevalence 22% [95% CI: 18–25%]). The prevalence of antimuscarinic or mirabegron use was 29% (95% CI: 26–33%). Urodynamic and renal function data were not collected. ConclusionsOur population-based description of urological management in Swiss SCI centers utilizing the EAU Guidelines on Neuro-Urology may be used as a reference for evaluation in other settings. Data further indicate a need for sex-specific neuro-urological management research. Patient summaryAt discharge from spinal cord injury (SCI) rehabilitation, a majority of patients have lower urinary tract problems, especially those with complete SCI. Women have a higher risk of urinary incontinence.

Efficacy of Mirabegron as Medical Expulsive Therapy for Distal Ureteral Stones: A Prospective, Randomized, Double-Blinded, Controlled Study

Background: Today, medical expulsive therapy (MET) is more effective and commonly used in distal ureteral stones when compared with conservative treatments. Many treatments, namely, alpha-adrenergic blockers and calcium channel blockers, prostaglandin synthesis inhibitors, glyceryl trinitrate, and steroids, have been, therefore, utilized to mitigate such complications and accelerate stone expulsion. Several animal and human studies revealed the presence of β3-receptors in the ureter and bladder, where stimulating these receptors could relax the distal ureteral segment. Objectives: The aim of the study was to evaluate the efficacy of use of mirabegron as MET for distal ureteral stones (intramural and extramural). Methods: This is a prospective randomized controlled study including 90 patients who had distal ureteral stones less than 10 mm and were evaluated between January and June 2020. The patients were classified into 3 groups: group (A) 30 patients: mirabegron 50 mg d−1 + diclofenac Na 100 mg tab (to be taken only during colic episodes), group (B) 30 patients: tamsulosin HCL 0.4 mg cap + diclofenac Na 100 mg tab (to be taken only during colic episodes), and group (C) 30 patients: diclofenac Na 100 mg tab only (to be taken only during colic episodes). Age, sex, stone size, laterality, and grade of ureterohydronephrosis were recorded. Patients were observed for 30 days, and ureteroscopy was completed for those with nonexpulsed stones. Follow-up parameters included number of renal colic episodes, duration of medical therapy, stone expulsion time, and stone expulsion rate (SER). Results: In the group (A), 2 (6.6%) patients were excluded due to nasal congestion, and 1 (3.3%) patient was excluded due to a 20-mm Hg systolic blood pressure increase. Four (13.3%) patients in group (B) were noncompliant on medical treatment. In addition, 2 (6.6%) patients in group (A), 1 (3.3%) patient in group (B), and 5 (16.6%) patients in group (C) who did not attend follow-up examinations were excluded from the study. The SER increased significantly in group (A) and (B) when compared with group (C). The mean time of stone expulsion was about 15, 25, and 12 days for groups A, B, and C, respectively, and there was a significant statistical difference (p value = 0.006) among the 3 groups. The mean number of renal colic episodes of group (A) of patients was 1.8 times, while that of group (B) was 2.6 times and that of group (C) was 2.16 times with no significant statistical difference after comparing the 3 groups (p value = 0.660). Conclusions: Treatment with mirabegron appears to be a safe and effective medical expulsion therapy for distal ureteric stones and is better than tamsulosin.

Risk of overactive bladder associated with cholinesterase inhibitors in dementia

Although cholinesterase inhibitors (ChEIs) are the primary treatment for dementia, they are associated with overactive bladder (OAB), necessitating antimuscarinic use. Limited data exist regarding the risk of OAB across individual ChEIs in dementia. This study evaluated the risk of OAB associated with individual ChEIs in older adults with dementia. This was a new user retrospective cohort study using Medicare claims data involving Parts A, B, and D claims dataset from 2013 to 2015. The study included older adults (aged 65 and older) with a diagnosis of dementia using donepezil, galantamine, or rivastigmine. New ChEI claims were identified with a 6-month baseline washout period. Patients with OAB diagnosis or any antimuscarinic or mirabegron use in the baseline period were excluded. The primary outcome of interest was OAB diagnosis or prescription of antimuscarinics or mirabegron within 6 months of ChEI initiation. Multivariable cox proportional hazards regression with propensity scores (PS) as covariates and inverse probability of treatment weighting generated using generalized boosted models was used to assess the risk of OAB among donepezil, galantamine, and rivastigmine users. The study included 524,975 older adults with dementia who were incident users of ChEIs (donepezil 80.72%, rivastigmine 16.41%, galantamine 2.87%). Overall, OAB diagnosis/antimuscarinic/mirabegron prescription was observed in 5.07% of the cohort within 6 months of ChEIs prescription. The Cox regression model with PS as covariate approach found that donepezil use increased the risk of OAB compared to rivastigmine (aHR, 1.13; 95% CI, 1.08-1.28; p < 0.0001). However, there was no differential risk of OAB between galantamine and rivastigmine. The findings were consistent with the generalized boosted models. The study found that the risk of OAB varies across individual ChEIs with an increased risk of OAB with donepezil compared to rivastigmine. The study findings suggest the need to understand and manage medication-related morbidity in older adults with dementia.

β3-Adrenoceptor Agonist for the Treatment of Bladder Dysfunction in Children: A Systematic Review and Meta-Analysis.

ß3-adrenergic receptor agonists (ß3 agonists) have been used in treatment of overactive bladder (OAB) and neurogenic detrusor overactivity (NDO) in adults. However, their use in children has only recently been approved by the U.S. Food and Drug Administration for patients with NDO. As in adults, the role of ß3 agonists in children may include conditions such as OAB. This systematic review and meta-analysis aims to understand the intended use, efficacy and safety of ß3 agonists in the pediatric population. A literature search was performed in February 2021 across MEDLINE®, Embase®, Scopus®, the Cochrane Library and ClinicalTrials.gov. No language restrictions were placed. All records describing the clinical use of ß3 agonists in pediatric patients (<18 years of age) were included, regardless of the methodological design or outcomes assessed. The identified records were screened by 2 independent authors. The reporting was compliant with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Data extraction was performed by 2 independent reviewers, blinded to each other's extractions. The data were pooled using the fixed effects model. Of 367 records identified, 8 studies were included in the review (3 prospective and 5 retrospective). ß3 agonists led to improvements in both urodynamics parameters and self-reported outcomes such as incontinence. Commonly reported side effects were headaches (3%‒5.9%), constipation (3.5%‒5.7%), rhinitis/nasopharyngitis (1.7%‒5.8%) and blurred vision (1.7%‒2.9%). Clinically meaningful changes in safety outcomes (blood pressure, heart rate, electrocardiogram-related changes, liver function) were rare. Before and after ß3 agonist use, pooled effect estimates for maximum cystometric capacity for 171 patients were mean difference of +98.84 ml (95% CI 74.72, 122.96); for complete dryness, assessment of 235 patients showed a Peto odds ratio of 8.68 (95% CI 5.22, 14.45). ß3 agonists appear to be a promising, effective and safe alternative/adjunctive therapy in management of pediatric NDO or OAB, with improvements in both objective urodynamics parameters and subjective patient-reported outcomes following their use.

Cardiovascular Risk in Users of Mirabegron Compared with Users of Antimuscarinic Treatments for Overactive Bladder: Findings from a Non-Interventional, Multinational, Cohort Study.

IntroductionDuring clinical trials, mirabegron, a β3-adrenoreceptor agonist, was associated with increased vital signs vs placebo in patients with overactive bladder.ObjectiveThe purpose of this study was to compare incidence rates of adverse cardiovascular (CV) outcomes following mirabegron or antimuscarinic use.MethodsWe conducted an observational post-marketing safety study utilising real-world data. The study population was identified within five sources: Danish and Swedish National Registers, Clinical Practice Research Datalink (UK), Optum (USA) and Humana (USA). Episodes of time when patients were new users of mirabegron or antimuscarinics (October 2012–December 2018) were sourced from prescriptions and matched on propensity scores. Occurrences of major adverse cardiovascular events (MACE), acute myocardial infarction (AMI), stroke, CV mortality and all-cause mortality were identified. Outcome incidence rates and hazard ratios from Cox models were estimated.ResultsOverall, 152,026 mirabegron and 152,026 antimuscarinic episodes were matched. The population consisted of 63.1% women and 72.6% were ≥ 65 years old. There were no appreciable differences in the incidence rates of MACE, AMI or stroke between users of mirabegron and antimuscarinics. Incidence rates of CV mortality (hazard ratio 0.83, 95% confidence interval 0.73–0.95) and all-cause mortality (hazard ratio 0.80, 95% confidence interval 0.76–0.84) were no higher with mirabegron vs antimuscarinics. Results restricted to episodes at high risk for CV events or stratified by age (< 65 years, ≥ 65 years) or prior overactive bladder medication use were consistent with overall findings.ConclusionsThis large, multinational study found no higher risk of MACE, AMI, stroke, CV mortality or all-cause mortality among users of mirabegron relative to users of antimuscarinics.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40264-021-01095-7.

The effect of Mirabegron and Duloxetine combination in mixed-type urinary incontinence treatment.

Stress-type and urgency-type urinary incontinence are seen together in mixed-type urinary incontinence. Treatment is usually chosen according to the predominant type of incontinence. The aim of this study is to evaluate the effect of mirabegron and duloxetine combination in the treatment of mixed-type urinary incontinence. The data of 88 mixed-type urinary incontinence patients who applied to the urology outpatient clinic between January 2018 and December 2019 were retrospectively analyzed. We applied mirabegron and duloxetine treatment to the patients. The International Consultation of Incontinence Questionnaire-Short Form, Overactive bladder symptom score questionnaire and daily pad count were statistically evaluated before and after the treatment. Statistically significant improvements were observed using the questionnaire forms and decreased daily pad usage after the eight-week treatment (p<0.001). Based on the clinical global effect scale, 62.50% of patients had a partial or complete response to treatment and also the use of daily pads were decreased from 3.7-0.89 on an average. Combination use of mirabegron and duloxetine in the treatment of mixed-type urinary incontinence improved symptom scores and decreased pad usage.

A study of cancer occurrence in users of mirabegron and antimuscarinic treatments for overactive bladder

Objective This post-authorization safety study (EU PAS Register Number: EUPAS16088) was designed to compare the incidence of cancer outcomes in patients treated with mirabegron versus antimuscarinic medications. Methods Cohorts of mirabegron initiators during 2012–2018 were propensity-score matched to antimuscarinic medication initiators within real-world data sources (Danish National Registers, Swedish National Registers, Clinical Practice Research Datalink [UK], Optum [US], and Humana [US]). Incident cancer cases were identified during follow-up from direct linkage to cancer registers or validated through medical record review or through physician questionnaires. Comparisons of sex-specific composite cancer outcomes (cancer of the lung/bronchus, colon/rectum, melanoma of skin, urinary bladder, non-Hodgkin lymphoma, kidney/renal pelvis, pancreas, prostate in men and breast and uterus in women) were made overall and for person-time in the first year and after the first year following start of treatment, for all ages and for the subgroup ≥65 years. Results Among the 80,637 mirabegron initiators matched to 169,885 antimuscarinic medication initiators, 68% were at least 65 years of age and 66% were women. Over 5000 incident cancer cases were observed overall. Incidence rates were higher for men than women for composite and individual cancer outcomes. The pooled fixed effects hazard ratios for composite cancer outcomes (all ages) were 1.05 (95% confidence interval [CI]: 0.98–1.14) for women and 1.06 (95% CI: 0.98–1.14) for men. Results were similar in persons ≥65 years. Conclusions The results suggest no association between mirabegron use and risk of cancer, compared with antimuscarinic medications, in either men or women. Registration: EU PAS Register Number: EUPAS16088

Long-term effectiveness of an intervention to enhance mirabegron use revision and its deprescribing: 36-month follow-up of a quasi-experimental trial in primary care

Objective This is a follow-up study from a multicenter, prospective, before-and-after quasi-experimental, controlled trial to assess effectiveness at 36 months of an intervention designed to promote the revision and deprescribing of mirabegron in primary care in patients with overactive bladder. Methods Intervention included patients who attended in 17 PHCs located in North Barcelona; control included patients who attended in the other 34 PHCs located in South, East and West Barcelona. The primary endpoint was mirabegron review and deprescribing when GPs considered appropriate, which was measured by the percentage of change of the number of patients with treatment at 36 months compared to the baseline. The intervention consisted of meetings with all the directors of the PHCs; distribution of the infographic to the GPs; providing information regarding the intervention for urologist and gynaecologist; and review of the treatments by the GPs. A monthly follow-up was done during the first year, and every three months thereafter until month 36. Results Overall, 1932 patients were included, mean age 71.6 years (female 53.8%). A total of 540 patients included in the intervention discontinued mirabegron at some point during the 36 months follow-up (540/762, 70.8%) compared to 759 patients in the control (759/1170, 64.9%), (p < 0.001). A total of 324/433 patients (74.8%) who discontinued mirabegron use at 12 months remained without pharmacological treatment at 36 months. With respect to the baseline cohort, there was a lower introduction of new patients with mirabegron in the intervention (546/762, 71.6%) compared to the control (1246/1170, 106.5%), (p < .001). Regarding the treated patients, there was an increase of 41.6% in the control and a slight increase of 0.8% in the intervention at 36 months, (p < .001). Conclusion Our data indicate that an intervention can enhance the review use of mirabegron in the primary care setting, and promote their deprescribing.

Efficacy and Safety of Mirabegron in Men with Overactive Bladder Symptoms and Benign Prostatic Hyperplasia.

To review the efficacy and safety of mirabegron in men with overactive bladder (OAB) and benign prostatic hyperplasia (BPH). Numerous studies have shown mirabegron to be efficacious and safe in treating symptoms of OAB. More recent studies evaluating the use of mirabegron in men with OAB and BPH have also shown the medication to be effective with few adverse side effects when used as monotherapy or in combination therapy. Mirabegron is an effective and safe treatment for men with OAB and BPH.

Effects of mirabegron on JJ stent-related symptoms: A multicentric study.

To investigate the effect of mirabegron 50mg/daily for JJ stent-related symptoms after ureteroscopic stone surgery. Medical records of 145 patients who were given a single daily oral dose of 50mg of mirabegron for relieving stent-related symptoms were retrospectively analysed. Demographic and clinical data and stone parameters were recorded. All participants completed the Turkish version of the Ureter Symptom Score Questionnaire (USSQ-T) on the postoperative 7th day, and again after at least 3weeks, before JJ stent removal. The severity of stent-related symptoms was statistically compared before and after the mirabegron treatment. The mean urinary symptoms score decreased significantly from 30.87±9.43 to 22.61±6.78 (P<.0001), mean body pain score decreased significantly from 21.82±11.22 to 14.03±7.52 (P<.0001), mean work performance score decreased from 10.50±8.61 to 7.02±6.51 (P<.0001) and mean general health score decreased significantly from 15.43±6.50 to 11.12±3.70 (P<.0001). The mean sexual matters score significantly decreased from 3.88±3.40 to 2.48±2.03 (P<.0001), the additional problem score decreased from 9.31±4.61 to 6.51±2.83 (P<.0001) and the overall quality of life (QoL) score decreased from 5.18±1.94 to 4.23±1.71 after mirabegron use (P<.0001). Daily use of 50g of mirabegron significantly improved stent-related symptoms, sexual matters and quality of life.

Overactive bladder medication: Persistence, drug switching, and reinitiation.

To assess real-world treatment profiles, including the time to and reasons for discontinuation or drug switching, treatment reinitiation, and postdiscontinuation follow-up in patients receiving antimuscarinics or ß3-agonists for overactive bladder (OAB) through a retrospective chart review. We retrospectively reviewed medical charts of 777 patients, aged≥18 years, who underwent antimuscarinic or ß3-agonist therapy at our hospital. Data on patient's age, sex, chief complaint, and OABsymptom score at therapy initiation were collected. Treatment persistence was assessed with respect to the median time to discontinuation and the persistence rate at 12 months. Older patients, male patients, and those with more severe urgency symptoms were more likely to show treatment persistence with OAB medications. Treatment persistence with mirabegron was significantly longer than that with antimuscarinics when administered as either the first- or second-line medication. Multivariate analyses showed that urgency severity and use of mirabegron were independently associated with better persistence (p = .026 and p = .018, respectively). Out of 583 patients who discontinued medication, 344 continued with the visit schedule, and the reinitiation rate of the OAB medication was 19% at a median follow-up of 24 months. Although the persistence rates for OAB medications improved with the introduction of mirabegron, most patients still discontinued the medication therapy within 1 year. The treatment strategies for patients with mild symptoms and those who are resistant to medication can still be improved. Tailored individualized treatments that avoid excessive reliance on pharmacotherapy would be key to further improve treatment outcomes in OAB patients.

Mirabegron Role in Urolithiasis Management: What you should Know

AbstractThe purpose of the present study was to develop a narrative review of the available evidence of mirabegron efficacy in three scenarios: as a medical expulsive therapy; as a medical treatment to increase a successful access to stones before ureteroscopy, and management of double-J stent-related symptoms. Only two original studies have evaluated its use as a medical expulsive therapy, with contradictory results in terms of stone expulsion rate; however, both demonstrated a better pain control in the mirabegron group. One randomized controlled trial (RCT) found a higher successful access to ureteral stones when mirabegron was administered 1 week before the ureteroscopy. And two RCTs demonstrated its efficacy in diminishing discomfort related with double-J stent. There is a promising role for the use of mirabegron in the arsenal of urolithiasis treatment, even as a medical expulsive therapy, before ureteroscopy surgery, to increase the successful access to the stones and after the placement of ureteral catheter to reduce the related symptoms. However, larger-scaled prospective double-blinded RCTs are needed before it can be used with these purposes in the clinical scenario.

Evaluating the Effectiveness of an Additional Risk Minimization Measure to Reduce the Risk of Prescribing Mirabegron to Patients with Severe Uncontrolled Hypertension in Four European Countries.

BackgroundMirabegron, indicated for the treatment of overactive bladder, is contraindicated in patients with severe uncontrolled hypertension (systolic blood pressure ≥180 mm Hg and/or diastolic blood pressure ≥110 mm Hg). In September 2015, a Direct Healthcare Professional Communication (DHPC) letter was disseminated as an additional risk minimisation measure.PurposeTo assess the effectiveness of the DHPC in reducing the proportions of patients with severe or non-severe uncontrolled hypertension at mirabegron initiation.MethodsAn observational multi-database cohort study was undertaken using routinely collected healthcare data (December 2012–December 2016) from the PHARMO Database Network (Netherlands), SIDIAP database (Spain), CPRD (United Kingdom, UK) and national healthcare registers and electronic medical records from Finland. DHPC effectiveness was evaluated using interrupted time series analyses comparing trends and changes in monthly proportions of severe or non-severe uncontrolled hypertensive mirabegron initiations relative to the timing of the DHPC dissemination.ResultsThe study population comprised 52,078 patients. Prior to DHPC dissemination, across the four databases, 0.3–1.3% had severe uncontrolled hypertension. Estimated absolute changes (EAC) in proportions of severe uncontrolled hypertension post-DHPC indicated a tendency towards a lower proportion in the Netherlands (EAC −0.36%, p=0.053), unchanged proportions in Spain and the UK and a higher proportion in Finland (EAC +0.73%, p=0.016). For non-severe uncontrolled hypertension (13–16% pre-DHPC), post-DHPC proportions tended to be lower in the Netherlands (EAC −2.02%, p=0.038) and Spain (EAC −1.04%, p=0.071), and unchanged in the UK and Finland.ConclusionSevere uncontrolled hypertension prior to mirabegron initiation was uncommon in these four European countries even before DHPC dissemination. This suggests that other risk minimisation communications (prior to the DHPC dissemination) had worked adequately with respect to minimising mirabegron use among patients with severe uncontrolled hypertension. No strong and consistent evidence of further risk minimisation after the DHPC dissemination was observed in this study.