Combination Treatment with Mirabegron and Solifenacin in Patients with Overactive Bladder: Efficacy and Safety Results from a Randomised, Double-blind, Dose-ranging, Phase 2 Study (Symphony)

Abrams, Paul; Kelleher, Con; Staskin, David R.; Rechberger, Tomasz; Kay, Richard; Martina, Reynaldo; Newgreen, Donald; Paireddy, Asha; Maanen, Rob van; Ridder, Arwin

doi:10.1016/j.eururo.2014.02.012

Cited by 212 publications

(205 citation statements)

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“…The first of these was the SYMPHONY study: a phase II study investigating use of mirabegron in various doses in combination with solifenacin. This study showed greater improvements in mean voided volume, frequency and urgency with combination therapy as opposed to monotherapy with solifenacin [Abrams et al 2015]. More recently a phase IV study has been published from a Japanese group (the MILAI study), looking at mirabegron as add-on therapy to solifenacin in patients with OAB symptoms that have not been controlled just by solifenacin [Yamaguchi et al 2015].…”

Section: Efficacy In Combinationmentioning

confidence: 99%

Mirabegron in overactive bladder patients: efficacy review and update on drug safety

Warren

Burden

Abrams

2016

Therapeutic Advances in Drug Safety

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Overactive bladder is a common condition, which significantly affects people's quality of life. The use of anticholinergic medication has been the mainstay of managing overactive bladder when conservative measures are not enough. Many patients stop anticholinergic medication because of the side effects and more recently the concerns about the effect of an anticholinergic burden and the development of dementia have been studied. Activation of β3 adrenoceptors has been shown to relax the detrusor muscle and subsequently lead to the development of the first β3 adrenoceptor agonist. Mirabegron is the first drug in this class to be approved for the use in overactive bladder. It has been extensively studied in phase II and III trials and has significant improvement in key overactive bladder parameters when compared with placebo. The incidence of side effects such as constipation, hypertension and tachycardia were comparable to anticholinergic medication but there was significantly less dry mouth incidence in the mirabegron groups. Mirabegron has been shown to be used safely in combination with solifenacin and tamsulosin. Head-to-head studies comparing efficacy and safety of mirabegron with anticholinergic medication would further help in the management strategy for overactive bladder.

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Section: Efficacy In Combinationmentioning

confidence: 99%

Mirabegron in overactive bladder patients: efficacy review and update on drug safety

Warren

Burden

Abrams

2016

Therapeutic Advances in Drug Safety

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“…Second, to enable inhibition by an increased cholinergic tone in overactive bladder, a combination with a muscarinic antagonist appears promising. Clinical data will be required to test this concept, and initial data are emerging (Abrams et al, 2014).…”

Section: Therapeutic Opportunitiesmentioning

confidence: 99%

The Odd Sibling: Features ofβ₃-Adrenoceptor Pharmacology

2014

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b 3 -Adrenoceptor agonists have recently been introduced for the treatment of overactive urinary bladder syndrome. Their target, the b 3 -adrenoceptor, was discovered much later than b 1 -and b 2 -adrenoceptors and exhibits unique properties which make extrapolation of findings from the other two subtypes difficult and the b 3 -adrenoceptor a less-understood subtype. This article discusses three aspects of b 3 -adrenoceptor pharmacology. First, the ligand-recognition profile of b 3 -adrenoceptors differs considerably from that of the other two subtypes, i.e., many antagonists considered as nonselective actually are b 3 -sparing, including propranolol or nadolol. Many agonists and antagonists classically considered as being b 3 -selective actually are not, including BRL 37,344 ( (6) . Moreover, the binding pocket apparently differs between the human and rodent b 3 -adrenoceptor, yielding considerable species differences in potency. Second, the expression pattern of b 3 -adrenoceptors is more restricted than that of other subtypes, particularly in humans; this makes extrapolation of rodent findings to the human situation difficult, but it may result in a smaller potential for side effects. The role of b 3 -adrenoceptor gene polymorphisms has insufficiently been explored and may differ even between primate species. Third, b 3 -adrenoceptors lack the phosphorylation sites involved in agonist-induced desensitization of the other two subtypes. Thus, they exhibit downregulation and/or desensitization in some, but not other, cell types and tissues. When desensitization occurs, it most often is at the level of mRNA or signaling molecule expression. All three of these factors have implications for future studies to better understand the b 3 -adrenoceptor as a novel pharmacological target.

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“…They demonstrated that in comparison with the monotherapy the combination of solifenacin and mirabegron leads to a significant improvement in the OAB symptoms such as mean volume voided per micturition, micturition frequency, and urgency without showing considerable additional harms. 85 Due to the relative low mean age of the randomized groups (mean age within the groups 53.4-56.5 years), this study does not comply with our definition of elderly patients. But given the promising results, we think this approach is worth mentioning, even though we recognize a strong need for further studies to establish efficacy in elderly patients.…”

mentioning

confidence: 57%

Treatment of Overactive Bladder in Elderly Patients: Clinical Considerations

2015

Clinical Medicine Insights: Geriatrics

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Overactive bladder (OAB) is a highly prevalent disorder among elderly and frail elderly patients, who are frequently polymedicated, suffer from kidney and liver failure and are susceptible to adverse events. Particular attention is, therefore, being given to efficacy and side effects of the treatment in patients older than 75 years. The introduction of newly developed drugs specifically designed for the treatment of OAB is opening new frontiers on this respect. The authors summarize the most recent evidence on this topic.

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Combination Treatment with Mirabegron and Solifenacin in Patients with Overactive Bladder: Efficacy and Safety Results from a Randomised, Double-blind, Dose-ranging, Phase 2 Study (Symphony)

Cited by 212 publications

References 15 publications

Mirabegron in overactive bladder patients: efficacy review and update on drug safety

Mirabegron in overactive bladder patients: efficacy review and update on drug safety

The Odd Sibling: Features ofβ₃-Adrenoceptor Pharmacology

Treatment of Overactive Bladder in Elderly Patients: Clinical Considerations

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Combination Treatment with Mirabegron and Solifenacin in Patients with Overactive Bladder: Efficacy and Safety Results from a Randomised, Double-blind, Dose-ranging, Phase 2 Study (Symphony)

Cited by 212 publications

References 15 publications

Mirabegron in overactive bladder patients: efficacy review and update on drug safety

Mirabegron in overactive bladder patients: efficacy review and update on drug safety

The Odd Sibling: Features ofβ3-Adrenoceptor Pharmacology

Treatment of Overactive Bladder in Elderly Patients: Clinical Considerations

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The Odd Sibling: Features ofβ₃-Adrenoceptor Pharmacology