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.

Uso de recursos y costes sanitarios en pacientes con vejiga hiperactiva que inician tratamiento con mirabegrón o un antimuscarínico en monoterapia en Cataluña: estudio MIRACAT / Resource use and healthcare costs in patients with overactive bladder who initiate treatment with mirabegron or antimuscarinic monotherapy in Catalonia: the MIRACAT study

Introducción y objetivo La vejiga hiperactiva (VH) impacta negativamente en la calidad de vida de los pacientes y puede asociarse a un elevado consumo de recursos. Nuestro objetivo fue describir el uso de recursos, costes y persistencia asociados al tratamiento de la VH con mirabegrón (MB) o antimuscarínicos (AM).Materiales y métodos Estudio observacional retrospectivo en registros médicos en adultos que iniciaron tratamiento para VH con MB o AM en Cataluña. Se analizó el uso de recursos sanitarios (visitas, hospitalizaciones, pruebas, medicación, absorbentes para incontinencia) en el primer año tras el inicio del tratamiento, estimando sus costes asociados (€, 2019) y la persistencia terapéutica. Se definió abandono como la falta de prescripción durante ≥ 45 días o el cambio de tratamiento.Resultados El coste medio por paciente (desviación estándar [DE]) con MB fue 1.640,20 € (1.227,60) vs. 2.159,20 € (2.264,60) con AM; el coste asociado al uso de recursos sanitarios fue inferior en MB vs. AM, exceptuando el coste del tratamiento farmacológico con MB. La persistencia al tratamiento a los 12 meses fue superior en MB (42,1 vs. 33,0%), así como el tiempo (mediana) hasta el abandono del tratamiento: 299 (IC 95%: 270,11-327,89) vs. 240 días (IC 95%: 230,46-249,54).Conclusiones Los pacientes tratados con MB mostraron menor uso de recursos, resultando en un coste medio por paciente/año más bajo, a pesar del mayor coste del fármaco respecto a AM. La mayor persistencia al tratamiento y el uso racional de las terapias disponibles mejoran el manejo de la VH y la calidad de vida de los pacientes (AU)

Introduction and aim Overactive bladder (OAB) negatively impacts patient quality of life and may be associated with high resource use. Our aim was to describe the resource use, costs and persistence associated with mirabegron (MB) or antimuscarinic (AM) treatment in patients with OAB.Materials and methods Observational retrospective study of medical records in adult patients initiating OAB treatment with MB or AM in Catalonia. Healthcare resource use (visits, hospital stays, tests, medication, absorbent pads) in the first year after treatment initiation was collected. Associated costs were estimated (€, reference year 2019), as well as treatment persistence. Treatment discontinuation was defined as the absence of prescription for at least 45 days or treatment change.Results The mean cost per patient (SD) was € 1,640.20 (€ 1,227.60) with MB and € 2,159.20 (€ 2,264.40) with AM; the associated healthcare resource use cost was lower with MB compared to AM, except for OAB drug costs. Persistence after 12 months of treatment initiation was higher in MB (42.1%) compared to AM (33.0%), as was the median time until treatment discontinuation: 299 (95% CI: 270-328) vs 240 days (95% CI: 230-250).Conclusions Lower healthcare resource use was observed with MB compared to AM in the first year of index treatment, resulting in a lower mean direct cost per patient and year, despite its higher acquisition cost. Increased treatment persistence, as well as rational use of available treatments improves OAB management and, in return, patients’ quality of life (AU)

Resource use and healthcare costs in patients with overactive bladder who initiate treatment with mirabegron or antimuscarinic monotherapy in Catalonia: the MIRACAT study.

INTRODUCTION AND AIM: Overactive bladder (OAB) negatively impacts patient quality of life and may be associated with high resource use. Our aim was to describe the resource use, costs and persistence associated with mirabegron (MB) or antimuscarinic (AM) treatment in patients with OAB. MATERIALS AND METHODS: Observational retrospective study of medical records in adult patients initiating OAB treatment with MB or AM in Catalonia. Healthcare resource use (visits, hospital stays, tests, medication, absorbent pads) in the first year after treatment initiation was collected. Associated costs were estimated (є, reference year 2019), as well as treatment persistence. Treatment discontinuation was defined as the absence of prescription for at least 45 days or treatment change. RESULTS: The mean cost per patient (SD) was є 1,640.20 (є 1,227.60) with MB and є 2,159.20 (є 2,264.40) with AM; the associated healthcare resource use cost was lower with MB compared to AM, except for OAB drug costs. Persistence after 12 months of treatment initiation was higher in MB (42.1%) compared to AM (33.0%), as was the median time until treatment discontinuation: 299 (95% CI: 270-328) vs 240 days (95% CI: 230-250). CONCLUSIONS: Lower healthcare resource use was observed with MB compared to AM in the first year of index treatment, resulting in a lower mean direct cost per patient and year, despite its higher acquisition cost. Increased treatment persistence, as well as rational use of available treatments improves OAB management and, in return, patients' quality of life.

[Analysis of costs and consequences related to the persistence of Mirabegron and antimuscarinic treatments and their impact on quality of life in patients with overactive bladder in Spain: Results of a probabilistic model.] / Análisis de costes y consecuencias relacionados con la persistencia del tratamiento con Mirabegrón y los fármacos antimuscarínicos y su impacto sobre la calidad de vida en los pacientes con vejiga hiperactiva en España: resultados de un modelo probabilístico.

OBJECTIVE: To evaluate whether the lower dropout rate of the treatment of overactive bladde r(OAB) with mirabegron could generate cost savings to the National Health System (NHS) and lead to quality-adjusted life years (QALYs) gains, compared to the most commonly prescribed antimuscarinics (AM) in Spain (tolterodine, fesoterodine, oxybutynin, solifenacin). METHODS: A probabilistic model (second order Monte Carlo simulation) in a hypothetical cohort of 1,000 patients with OAB and a time horizon of 1 year was carried out. Discontinuation and persistence rates for both mirabegron and AM were obtained from a Spanish observational study in 1798 patients. Unit costs (€ 2018) and utility loss associated with treatment discontinuation were obtained from Spanish public prices and literature, respectively. RESULTS: Persistence rates in patients treated with mirabegron were twice as high compared to AM, leading to a QALY gain of 0.0151 ± 0.0007 per year. Treatment with mirabegron could generate savings of 80.74 ±4.61 € per patient per year compared to AM, assuming 100% probability of saving. The hypothetical substitution of AM treatment for mirabegron could potentially generate savings of 6.6 million euros (95% CI 3.9-10.1 million euros) to the NHS and 1,238 QALYs gains (CI95%731; 1,885 QALYs) within a period of 1 year. CONCLUSIONS: The probabilistic model presented showed a greater persistence in patients treated with mirabegron compared to AM, leading to a positive impactin patients quality of life, as well cost savings to the NHS in Spain.

OBJETIVO: Evaluar si la menor tasa de abandonos del tratamiento de la vejiga hiperactiva (VH) con mirabegrón podría generar ahorros para el Sistema Nacional de Salud (SNS) y ganancia de años de vida ajustados por calidad (AVACs), en comparación con los fármacos antimuscarínicos (AM) (tolterodina, fesoterodina, oxibutinina, solifenacina).MÉTODOS: Modelo probabilístico (simulación de Monte Carlo de segundo orden) en una cohorte hipotética de 1.000 pacientes con VH y un horizonte temporal  de 1 año. Las tasas de abandono/persistencia del tratamiento con mirabegrón y AM se obtuvieron de un estudio observacional español en 1.798 pacientes. Los costes unitarios (€ 2018) y la pérdida de utilidades ligada al abandono del tratamiento se obtuvieron de precios públicos españoles y de la literatura, respectivamente. RESULTADOS: En cada paciente tratado con mirabegrón se duplica la tasa de persistencia en comparación con los AM, ganándose anualmente 0,0151 ±0,0007 AVACs, frente a AM. Con mirabegrón se generaría un ahorro anual por paciente de 80,74 ± 4,61 € en comparación con los AM, con una probabilidad de ahorro del 100%. La sustitución hipotética de los AM por mirabegrón, generaría en el plazo de 1 año un ahorro para el SNS de 6,6 millones de euros (IC 95%3,9-10,1 millones de euros) y se ganarían 1.238 AVAC (IC95% 731; 1.885 AVAC). CONCLUSIONES: El modelo probabilístico muestra una mayor persistencia en pacientes tratados con mirabegrón en comparación con los AM, generando un impacto positivo sobre la calidad de vida de los pacientes así como ahorros para el SNS.

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.

[Cost effectiveness of Mirabegron and antimuscarinic drugs in patients with hiperactive bladder.] / Coste-efectividad de mirabegrón y los antimuscarínicos en pacientes con vejiga hiperactiva.

OBJECTIVE: To evaluate the costeffectivenessof mirabegron in comparison to theantimuscarinic drugs tolterodine, solifenacin andfesoterodine, in the treatment of urgency, increasedmicturition frequency and urinary incontinence in patientswith overactive bladder (OAB). MATERIAL AND METHODS: A Markov model in Excel,with a time horizon of 5 years was developed fromthe National Health System and societal perspective.Clinical effectiveness was estimated from a clinical trial(SCORPIO) and a network meta-analysis. Unit costswere obtained from Spanish sources. The effectivenessof the treatments was measured as quality adjusted lifeyears(QALY). Deterministic and probabilistic sensitivityanalyses were performed. RESULTS: For the 5-year time horizon, the incrementalcost per patient with mirabegron 50 mg versustolterodine was € 195.52 and € 157.42, from theNational Health System (NHS) and societal perspectivesrespectively, with a gain of 0.0127 QALY withmirabegron. Consequently, the cost of gaining a QALYwith mirabegron versus tolterodine was 15,432 € and12,425 € respectively. The probability that mirabegronwould be cost-effective at a willingness to pay thresholdof € 30,000 was: 70% (NHS) and 71% (society)versus tolterodine; 94% (NHS and society) versussolifenacin 5 mg; 84% (NHS) and 84.5% (society)versus solifenacin 10 mg; 96% (NHS and society)versus fesoterodine 4 mg; 98% (NHS) and 99% (society)versus fesoterodine 8 mg. The highest probability thatmirabegron would be cost-effective at a willingness topay threshold of € 20.000 and € 25.000 per QALYgained, is obtained versus fesoterodine 4 mg and 8 mgfrom both NHS and society perspectives. CONCLUSIONS: The treatment of patients with OABwith mirabegron 50 mg is likely to be cost-effectivecompared to treatment with antimuscarinics.

OBJETIVO: Evaluar el coste-efectividad de mirabegrón frente a los fármacos antimuscarínicos tolterodina, solifenacina y fesoterodina, en el tratamiento sintomático de la urgencia, el aumento de la frecuencia miccional y la incontinencia de urgencia en los pacientescon vejiga hiperactiva (VH).MÉTODOS: Modelo de Markov en Excel, con un horizonte temporal de 5 años, desde la perspectiva del Sistema Nacional de Salud y de la sociedad. La efectividad clínica se obtuvo de un ensayo clínico frente a tolterodina y de un metaanálisis. Los costes unitarios se obtuvieron de fuentes españolas. La efectividad de los tratamientos se midió como años de vida ajustados por calidad de vida (AVAC). Se realizaron análisis de sensibilidad determinísticos y probabilísticos. RESULTADOS: Para el horizonte temporal de 5 años, el coste incremental por paciente con mirabegrón 50 mg frente a tolterodina es de 195,52 € y 157,42 €, desde las perspectivas del Sistema Nacional de Salud (SNS) y social, respectivamente, con una ganancia de 0,0127 AVAC con mirabegrón. El coste de ganar un AVAC con mirabegrón frente a tolterodina sería de 15.432 € y de 12.425 €, respectivamente. La probabilidad de que mirabegrón sea coste-efectivo frente a tolterodina, sería del 70% y del 71%, respectivamente. Para el SNS, la probabilidad de coste-efectividad de mirabegrón frente a solifenacina 5 y 10 mg sería del 84% y del 84,5%, respectivamente y en comparación con fesoterodina 4 y 8 mg sería del 96% y 98%, respectivamente. CONCLUSIONES: El tratamiento de los pacientes con VH con mirabegrón 50 mg es probablemente coste- efectivo en comparación con el tratamiento con antimuscarínicos.

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.

Persistence and concomitant medication in patients with overactive bladder treated with antimuscarinic agents in primary care. An observational baseline study.

OBJECTIVE: To assess therapeutic persistence and its relationship with concomitant medication in patients treated with fesoterodine versus tolterodine and solifenacin for overactive bladder (OAB) in standard clinical practice conditions. MATERIAL AND METHODS: An observational, multicentre retrospective study was performed based on medical registries of patients followed-up in primary care (PC). Three study groups were analysed. Persistence was defined as the time (in months) without withdrawing from the initial therapy or without changing to another medication for at least 30 days after the initial prescription. The concomitant medications were antidepressants, anxiolytic/hypnotic agents, antibiotics, antiseptic agents, laxatives and skin products. We employed the SPSSWIN program version 17 (statistical significance, P<.05). RESULTS: We selected 3094 patients for the study. The median age was 54.0 years and 62.2% were women. The patients treated with fesoterodine shown greater treatment persistence (12 months) when compared with those who took solifenacin and tolterodine (40.2% vs. 34.7% and 33.6%, respectively; P=.008). They also showed a lower use of concomitant medication (1.1 vs. 1.2 and 1.2 drugs, respectively; percentages: 61.6% vs. 67.1% and 70.1%, respectively; P<.03). CONCLUSIONS: The patients undergoing OAB treatment with fesoterodine, when compared with those taking solifenacin and tolterodine, were associated with greater treatment persistence and a reduced use of concomitant medication.

Use of health care resources and associated costs in non-institutionalized vulnerable elders with overactive bladder treated with antimuscarinic agents in the usual medical practice.

OBJECTIVE: To evaluate the use of resources and health costs in vulnerable elderly institutionalized patients with overactive bladder (OAB) treated with fesoterodine, tolterodine or solifenacin in routine medical practice. MATERIAL AND METHODS: A multicenter retrospective study, from the records of patients treated during 2008-2010 in three geographical locations and starting treatment with antimuscarinic (fesoterodine, solifenacin and tolterodine) for OAB. The attribute of vulnerability was based on collecting at least 3 of the Vulnerable Elders Survey criteria-13, age>75 years, poor/average age for health and difficulty in at least one daily physical activity. MAIN MEASURES: morbidity, persistence and resource use and costs. Monitoring of patients was conducted over 52 weeks. A general linear model with covariates and bootstraping (1000) at random was used to construct the 95% CI of the cost differences between drugs. RESULTS: Records of 552 patients (50.8% women, mean age: 80.2 years) were analyzed. Treated with fesoterodine (N=58), solifenacin (N=252) or tolterodine (N=212). The use of absorbent was 20.7%, 29.4% and 33.0% (P=.186), respectively. Persistence to treatment was slightly greater with fesoterodine. The patient healthcare costs/year were lower with fesoterodine, €1,775 (1550-2014) vs. solifenacin €2,062 (1911-2223) and tolterodine €2,149 (1,978-2,307), P=.042, as a result of lower utilization visits and concomitant medication. CONCLUSIONS: Despite the potential limitations of the study, the vulnerable elderly non institutionalized patients with OAB treated with fesoterodine, compared to solifenacin or tolterodine were associated with lower resource utilization and healthcare costs.