Mirabegron and Anticholinergics in the Treatment of Overactive Bladder Syndrome: A Meta-analysis / Mirabegron e anticolinérgicos no tratamento da síndrome da bexiga hiperativa: metanálise

Abstract Objective To compare the use of mirabegron with anticholinergics drugs for the treatment of overactive bladder (OB). Data Source 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. Data Collection 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. Data Synthesis 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)]. Conclusion Mirabegron and antimuscarinics have comparable efficacy and adherence rates; however, mirabegron showed fewer total and isolated adverse events.

Resumo Objetivo Comparar o uso de mirabegrom com anticolinérgicos para o tratamento da bexiga hiperativa (BH). Fonte de Dados Buscas sistemáticas foram realizadas nas bases de dados EMBASE, PUBMED, Cochrane e LILACS desde o início até setembro de 2021. Incluímos ECR, mulheres com sintomas de BH clinicamente comprovados, estudos que compararam mirabegrom a medicamentos antimuscarínicos e avaliaram a eficácia, segurança ou adesão. Coleta de Dados RevMan 5.4 foi usado para combinar os resultados entre os estudos. Derivamos razões de risco (RRs) e diferenças médias com intervalo de confiança (IC) de 95% usando um modelo meta-analítico de efeitos aleatórios. Cochrane Collaboration Tool e GRADE foi aplicado para risco de viés e qualidade da evidência. Síntese dos Dados Foram incluídos 14 estudos com um total de 10.774 pacientes. Menos eventos adversos totais foram relatados no grupo mirabegrom do que no grupo antimuscarínicos [RR: 0,93 (0,89-0,98)]. O risco de distúrbios do trato gastrointestinal e boca seca foram menores com mirabegrom [RR: 0,58 (0,48-0,68); 9.375 pacientes; RR: 0,44 (0,35-0,56), 9.375 pacientes, respectivamente]. Nenhuma diferença foi relatada entre mirabegrom e drogas antimuscarínicos para eficácia. A adesão ao tratamento foi de 87,7% em ambos os grupos [RR: 0,99 (0,98-1,00)]. Conclusão Mirabegrom e antimuscarínicos têm eficácia e taxas de adesão comparáveis, porém o mirabegrom apresentou menos eventos adversos totais e isolados.

Assessment of Prescribing Practices in Overactive Bladder Pharmacotherapy across Different Specialties of India : A Prescription Trend Analysis

Purpose : To assess the temporal prescription patterns of overactive bladder (OAB) pharmacotherapy based on the prescription trend analysis amongst Indian clinicians. Methods : IQVIA (Quintiles and IMS Health) secondary sales audit (SSA) and prescription audit for antimuscarinics and beta-3 adrenoceptor agonist (mirabegron) from 2014 to 2022, were analyzed. Prescribers overlap analysis for solifenacin and mirabegron among Indian urologists was also analyzed. Results : Urologists’ prescription rates of OAB drugs were 65% in 2016 and 52% in 2022. The rate of OAB medication prescription by non-urologists was highest among surgeons (17%), followed by consultant physicians (9%) and gynecologists (8%) in 2022. In addition, among OAB medication prescription rates for antimuscarinics were 100% in 2016 and 56% in 2022 whereas for mirabegron, it was 0% in 2016 and 44% in 2022. The proportion of prescribers of OAB medication among urologists was 38% in 2016 and 33% in 2022. Exclusive prescribers of solifenacin were 748 in 2018 and 715 in 2022 at the urologist, whereas for mirabegron, it was 961 in 2018 and 1475 in 2022. Conclusions : Urologists remained a top prescribing specialty for OAB drugs, although prescription share increased among surgeons and consultant physicians. OAB medicines prescriptions by urologists are shifting from solifenacin to mirabegron. The results of this study could further help clinicians, to design the optimum treatment approach in OAB patients according to their need, which can help to lower antimuscarinic side effects, improves treatment adherence, and improves patient’s QoL.

Treatment of bladder dysfunction with solifenacin: is there a risk of dementia or cognitive impairment?

The use of bladder antimuscarinics is very common in the elderly. However, recent population-based studies that assessed the use of anticholinergics or bladder antimuscarinics showed an increased risk of dementia when these drugs were used for a prolonged period. Several of these population-based studies included patients who used solifenacin, which is a bladder antimuscarinic released in 2005 with the prospect of being a more selective antimuscarinic for M3 receptors (M3R), which could make it a safer drug when trying to avoid unwanted effects of older bladder antimuscarinics such as oxybutynin, especially with regard to changes in cognition. Since the various bladder antimuscarinics have distinct pharmacological characteristics, such as in the ability to penetrate the blood-brain barrier, in selectivity for muscarinic receptors, and in brain efflux mechanisms, their effects on the central nervous system (CNS) may vary. Solifenacin was the drug selected in this review, which aims to describe the results of several articles published in recent years reporting the effects of solifenacin on cognition or the risk of dementia development. Although preclinical studies show that solifenacin can also act on brain M1 receptors (M1R), short-term clinical studies have shown it to be safe for cognition. However, there are no long-term randomized studies that prove the safety of this drug for the CNS. Thus, until the safety of solifenacin has been established by long-term studies, it seems advisable to avoid prolonged use of this drug in elderly patients.

Custo-efetividade de mirabegrona no tratamento de primeira escolha da síndrome da bexiga hiperativa: uma análise sob a perspectiva do sistema de saúde brasileiro / Cost-effectiveness of mirabegron as first-choice treatment for overactive bladder syndrome: an analysis from the Brazilian health system perspective

Objetivo: Avaliar a relação de custo-efetividade de mirabegrona como tratamento de primeira escolha de pacientes adultos com síndrome da bexiga hiperativa (SBH) comparada a antimuscarínicos orais comumente prescritos no manejo dessa condição. Métodos: O modelo de Markov foi utilizado, com ciclos mensais e horizonte temporal de um ano, para analisar a relação de custo-efetividade de mirabegrona em comparação a tolterodina, oxibutinina, darifenacina e solifenacina. Os pacientes iniciaram o modelo em tratamento com mirabegrona ou um dos comparadores, sendo distribuídos em cinco níveis de gravidade da doença, de acordo com a frequência miccional e número de episódios de incontinência, e a cada ciclo mensal poderiam melhorar, piorar ou permanecer no mesmo nível de severidade do ciclo anterior. Os resultados foram apresentados por meio de uma razão de custo-efetividade incremental. Resultados: Considerando a perspectiva do sistema de saúde suplementar, o custo total do tratamento com mirabegrona foi de R$ 2.455,26 e os parâmetros de efetividade em 0,491 e 0,498 (melhora na gravidade da incontinência e frequência miccional, respectivamente), sendo mais efetivo que os comparadores. Com relação à perspectiva pública, foi estimado um custo com o tratamento de R$ 1.396,01, com características similares de efetividade. De maneira geral, o tratamento com mirabegrona foi dominante quando comparado à tolterodina e custo-efetivo na comparação com os demais antimuscarínicos, em ambas as perspectivas analisadas. Conclusão: Mirabegrona demonstrou ser a melhor opção para tratamento de primeira escolha da SBH com potencial de redução de custos ao longo do tempo, tanto para o sistema público quanto para o sistema de saúde suplementar brasileiro.

Objective: To assess the cost-effectiveness of mirabegron as first-choice treatment in adult patients with of overactive bladder (OAB) compared to oral antimuscarinics, usually prescribed for this condition. Methods: A Markov model has been adopted, with monthly cycles and a one-year time horizon, to analyze the cost-effectiveness of mirabegron compared to antimuscarinic agents: tolterodine; oxybutynin; darifenacin; and solifenacin. The model started with patients receiving treatment with mirabegron or one of the comparators and then, they were assigned to five disease severity levels according to micturition frequency and number of incontinence episodes, and within each monthly cycle they could improve, worsen or remain at the same symptom severity level. Results were presented using an incremental cost-effectiveness ratio. Results: Considering the Brazilian private perspective, treatment with mirabegron resulted in a total cost of R$ 2,455.26 and effectiveness parameters at 0.491 and 0.498 (improvement in incontinence severity and micturition, respectively), being more effective than the comparators. Regarding the Brazilian public perspective, treatment with mirabegron resulted in a total cost of R$ 1,396.01 with similar effectiveness estimation. In general, a dominance was observed when mirabegron was compared to tolterodine and a cost-effectiveness profile against the other muscarinic antagonists, considering both health perspectives. Conclusion: Mirabegron has proven to be the best option for OAB first-line treatment with potential cost savings over time for both the public and private health care systems in Brazil.

The Effectiveness of Anticholinergic Therapy for Overactive Bladders: Systematic Review and Meta-Analysis / Eficácia da terapia anticolinérgica na bexiga hiperativa: revisão sistemática e metanálise

Abstract The overactive bladder (OAB) has a significant negative impact on the quality of life of patients. Antimuscarinics have become the pharmacological treatment of choice for this condition. The objective of this systematic review and meta-analysis is to examine the evidence from randomized clinical trials about the outcomes of the antimuscarinic drugs available in Brazil on OABs. We searched MEDLINE and the Cochrane Central Register of Controlled Trials from the inception of these databases through to September 2015. The primary outcome measures were the mean decrease in urge urinary incontinence episodes and the mean decrease in the frequency of micturition. The results suggest that there is a moderate to high amount of evidence supporting the benefit of using anticholinergic drugs in alleviating OAB symptoms when compared with placebo. It is still not clear whether any of the specific drugs that are available in Brazil offer advantages over the others. These drugs are associated with adverse effects (dry mouth and constipation), although they are not related to an increase in the number of withdrawals.

Resumo A bexiga hiperativa determina um impacto negativo na qualidade de vida dos nossos pacientes. Os antimuscarínicos tornaram-se o tratamento farmacológico de escolha para essa condição. O objetivo desta revisão sistemática e metanálise é examinar as melhores evidências científicas sobre estas medicações disponíveis no Brasil no tratamento de mulheres com bexiga hiperativa. As bases de dados utilizadas foram MEDLINE e a biblioteca da Cochrane, das quais selecionamos os ensaios clínicos randomizados até setembro de 2015. Os principais desfechos analisados foram a diminuição dos episódios de incontinência urinária de urgência e a diminuição da frequência de micção. Os resultados sugerem que as drogas existentes no Brasil sustentam o benefício dos anticolinérgicos no alívio dos sintomas da bexiga hiperativa quando comparadas como placebo. Emtermos de eficácia, as medicações apresentam resultados semelhantes no controle dos sintomas. Essas drogas estão associadas a efeitos adversos importantes, tais como boca seca e constipação, e esses efeitos adversos não influenciaram no uso da medicação.

Comparison of α1-blocker monotherapy with α1-blocker and antimuscarinics add-on therapy for the treatment of overactive bladder secondary to BPH / 中华泌尿外科杂志

Objective Detrusor overactivity (DO) is one known cause of overactive bladder (OAB) symptoms in benign prostatic hyperplasia (BPH).In this study,OAB symptoms suggestive of DO in BPH were treated with α1-blocker monotherapy or α1-blocker and antimuscarinics add-on therapy,and the efficacy and safety were assessed.Methods BPH patients who suffered from OAB symptoms for at least 3 month were enrolled in a prospective self-control study from August 2010 to April 2012.The inclusion criteria are total international prostate symptom score (IPSS) ≥8,OAB Symptom Score (OABSS) ≥3,OABSS urgency score ≥2,Postvoid residual volume (PVR) ＜ 100 ml,and maximum urinary flow rate (Qmax) ≥ 5 ml/s.All the patients who met the inclusion criteria were treated with α1-blocker ( tamsulosin 0.2 mg/day or doxazosin 4 mg/day) for 2 weeks.After 2 weeks,patients with no symptomatic improvement ( OABSS≥3) underwent pressure-flow test,and those whose Pdet≥ 40 cm H2O and DO presented more than one time were added antimuscarinics (solifenacin 5 mg/day or tolterodine 4 mg/day) for an additional 2 weeks.OABSS,IPSS,QOL,Qmax and PVR were re-evaluated every 2 weeks.Results Ninety-four cases of BPH/OAB patients met the inclusion criteria and completed 4 weeks treatment.The baseline of total OABSS was 7.0 ± 1.3,IPSS was 17.0 ± 1.7,QOL was 5.0 ±0.7,Qmax was (8.8 ±2.5) ml/s and PVR was (86.0 ± 16.5) ml.After 2 weeks treatment with α1-blocker alone,OABSS was 5.2 ± 0.8,IPSS was 14.2 ± 1.9,QOLwas4.O±0.8,Qmaxwas (11.4±2.4) ml/s and PVR was (67.9±12.9) ml.After another2 weeks treatment with α1-blocker plus antimuscarinics,OABSS was 3.1 ± 0.8,IPSS was 11.1 ± 1.9,QOL was 3.1 ± 0.7,Qmax was ( 10.8 ± 2.4) ml/s and PVR was (71.8 ± 11.9 ) ml.Compared with baseline values,OABSS,IPSS,QOL,Qmax and PVR significantly improved (P ＜ 0.01 ) in α1-blocker monotherapy group and α1-blocker plus antimuscarinic group.The improvement of OABSS,IPSS,QOL scores of α1-blocker plus antimuscarinic group were greater than α1-blocker monotherapy group (p ＜ 0.05 ),while Qmax and PVR showed no differences between the two groups.No acute urinary retention (AUR) was deteted.Conclusion Both of α1-blocker monotherapy and α1-blocker with antimuscarinics add-on therapy can improve OAB symptoms.