Adrian Wagg

Persistence with prescribed antimuscarinic therapy for overactive bladder: a UK experience

Study Type – Therapy (prevalence)

Pelvic organ prolapse and overactive bladder

In this review we try to shed light on the following questions: How frequently are symptoms of overactive bladder (OAB) and is detrusor overactivity (DO) present in patients with pelvic organ prolapse (POP) and is there a difference from women without POP? Does the presence of OAB symptoms depend on the prolapsed compartment and/or stage of the prolapse? What is the possible pathophysiology of OAB in POP? Do OAB symptoms and DO change after conservative or surgical treatment of POP?

Randomised, Multicentre, Placebo-controlled, Double-blind Crossover Study Investigating the Effect of Solifenacin and Oxybutynin in Elderly People with Mild Cognitive Impairment: The SENIOR Study

BACKGROUND Compared with younger people, the elderly are more likely to suffer from overactive bladder (OAB) and to have other chronic conditions that affect physical or cognitive function. Despite this, there are few data on the cognitive safety of antimuscarinic agents in older patients and none that examine the effect of these agents on those with mild cognitive impairment (MCI). OBJECTIVE To evaluate cognitive effects during chronic stable dosing with solifenacin and oxybutynin versus placebo in older (≥75 yr) subjects with MCI. DESIGN, SETTING, AND PARTICIPANTS A randomised, double-blind, triple-crossover trial in 26 elderly volunteers with MCI. Cognitive function was assessed using Cognitive Drug Research (CDR) computerised testing. INTERVENTION Three treatment periods of 21 d each with solifenacin 5mg once daily, oxybutynin 5mg twice daily, or placebo, separated by 21-d washout periods. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary end point was change from baseline in cognitive function with solifenacin at 6h postdose and oxybutynin at 2h postdose (time points close to their predicted time to peak concentration). Secondary end points included change in cognitive function at additional time points, and safety and tolerability assessments. RESULTS AND LIMITATIONS Neither agent was associated with significant changes from baseline in any of the five standard, composite outcomes of cognitive function (power of attention, continuity of attention, quality of working memory, quality of episodic memory, and speed of memory). In a secondary analysis, oxybutynin was associated with significant decreases in power and continuity of attention versus placebo at 1-2h postdose. Both agents were well tolerated, with the most frequently reported adverse event being mild or moderate dry mouth. CONCLUSIONS Solifenacin had no detectable effect on cognition in this group of elderly people with MCI.

Flexible-dose fesoterodine in elderly adults with overactive bladder: results of the randomized, double-blind, placebo-controlled study of fesoterodine in an aging population trial.

To assess the efficacy and safety of flexible‐dose fesoterodine in elderly adults with overactive bladder (OAB).

The efficacy and tolerability of the β3-adrenoceptor agonist mirabegron for the treatment of symptoms of overactive bladder in older patients

INTRODUCTION mirabegron is a β3-adrenoceptor agonist developed for the treatment of symptoms of overactive bladder (OAB). As the prevalence of OAB increases with age, a prospective subanalysis of individual and pooled efficacy and tolerability data from three 12-week, randomised, Phase III trials, and of tolerability data from a 1-year safety trial were conducted in order to evaluate the efficacy and tolerability of mirabegron in subgroups of patients aged ≥65 and ≥75 years. METHODS primary efficacy outcomes were change from baseline to final visit in the mean number of incontinence episodes/24 h and the mean number of micturitions/24 h. Tolerability was assessed by the incidence of treatment-emergent adverse events (TEAEs). RESULTS over 12 weeks mirabegron 25 mg and 50 mg once-daily reduced the mean numbers of incontinence episodes and micturitions/24 h from baseline to final visit in patients aged ≥65 and ≥75 years. Mirabegron was well tolerated: in both age groups, hypertension and urinary tract infection were among the most common TEAEs over 12 weeks and 1 year. The incidence of dry mouth, a typical anticholinergic TEAE, was up to sixfold higher among the older patients randomised to tolterodine than any dose of mirabegron. CONCLUSIONS these analyses have demonstrated the efficacy of mirabegron over 12 weeks and the tolerability of mirabegron over 12 weeks and 1 year in OAB patients aged ≥65 and ≥75 years, supporting mirabegron as a therapeutic option in older patients with OAB.

Urinary incontinence in frail elderly persons: Report from the 5th International Consultation on Incontinence

Evidence based guidelines for the management of frail older persons with urinary incontinence are rare. Those produced by the International Consultation on Incontinence represent an authoritative set of recommendations spanning all aspects of management.

Review of cognitive impairment with antimuscarinic agents in elderly patients with overactive bladder

Overactive bladder (OAB) will become an increasingly prevalent problem as the proportion of older people in the population increases over the next 20 years. In addition to the urological symptoms (urinary urgency, with or without urgency incontinence, usually with increased daytime frequency and nocturia), OAB is associated with other problems in older patients, especially an increased risk of falls and fractures. The bother caused by OAB needs not be an inevitable consequence of ageing, because the symptoms can usually be alleviated, even in frail older people. Pharmacological treatment for OAB involves the use of antimuscarinic agents, whose efficacy and safety profiles depend on their interactions with muscarinic receptors that are widely distributed throughout the body. Interactions between antimuscarinics and M1 receptors in the central nervous system may have the potential to cause cognitive impairment in older people, depending on muscarinic receptor binding profiles, lipophilicity and the ability to cross the blood brain barrier. Concerns over the possibility of cognitive impairment have contributed to an under‐utilisation of antimuscarinics in the geriatric population, despite the high prevalence and severity of OAB in older subjects. Antimuscarinic agents should be actively considered for elderly patients with OAB, but it is desirable to establish the cognitive risk for every type of antimuscarinic, using robust cognition assessment methods.

Persistence and adherence with the new beta-3 receptor agonist, mirabegron, versus antimuscarinics in overactive bladder: Early experience in Canada

INTRODUCTION Antimuscarinics are the principal pharmacological treatment for overactive bladder (OAB), but frequently give rise to anticholinergic side effects, such as dry mouth, a factor leading to poor persistence. The β3-adrenoceptor agonist mirabegron is devoid of significant anticholinergic activity, while being effective in OAB. We evaluated persistence and adherence with mirabegron versus antimuscarinics over 12 months. METHODS We obtained retrospective claims from a Canadian Private Drug Plan database for patients 18 years old and over, with a first claim for mirabegron or antimuscarinics during a 6-month index period (April-September 2013). A 6-month look-back identified those with no prior claims for OAB medication (treatment-naïve) or ≥1 prior OAB drug (treatment-experienced). Time to end of persistence (≥30 day therapy gap or switch of therapy) was evaluated over 12 months; adherence with medication (medication possession ratio) was also measured. RESULTS Persistence data from 19 485 patients (74% female, 92% naïve, 19.9% aged ≥65 years) showed that for experienced patients the median number of days on mirabegron was 299 days, compared with a range of 96 to 242 days for the different antimuscarinics; for naïve patients, it was 196 versus 70 to 100 days, respectively. Persistence at 12 months was for mirabegron 39% versus 14% to 35% for antimuscarinics, (experienced) and 30% mirabegron versus 14% to 21% antimuscarinics, (naïve). Patients taking mirabegron demonstrated statistically significantly greater adherence than those taking antimuscarinics. CONCLUSION Patients who received mirabegron remained longer on treatment than those treated with antimuscarinics, and had higher 12-month persistence and adherence rates.

Cardiovascular Safety of β3-adrenoceptor Agonists for the Treatment of Patients with Overactive Bladder Syndrome

CONTEXT Mirabegron, the first β3-adrenoceptor agonist in clinical practice, is approved for treatment of overactive bladder (OAB) syndrome symptoms. Because β3-adrenoceptors are expressed in cardiovascular (CV) tissues, there are concerns that OAB treatment with β3-adrenoceptor agonists may affect the heart and vasculature. OBJECTIVE To provide a summary of CV effects of β3-adrenoceptor agonists in clinical studies. EVIDENCE ACQUISITION A systematic literature search from inception until November 2014 was performed on studies in PubMed and Medline. EVIDENCE SYNTHESIS Twenty papers, published between 1994 and 2014, were identified: mirabegron (16), solabegron (2), AK-677 (1), and BRL35135 (1). More detailed CV data from mirabegron studies were available in online regulatory documents filed with the US Food and Drug Administration and the UK National Institute for Health and Care Excellence. CONCLUSIONS The CV safety of mirabegron appears to be acceptable at therapeutic doses and comparable with that of antimuscarinic agents, currently first-line therapy for OAB. PATIENT SUMMARY In this review we looked at the cardiovascular (CV) effects of β3-adrenoceptor agonists used for the treatment of overactive bladder (OAB). The CV safety of mirabegron (the only clinically approved β3-adrenoceptor agonist) appears to be acceptable at therapeutic doses and comparable with that of antimuscarinic agents, the current first-line therapy for OAB.

Long-term safety, tolerability and efficacy of flexible-dose fesoterodine in elderly patients with overactive bladder: open-label extension of the SOFIA trial.

To assess the long‐term safety, tolerability, and efficacy of flexible‐dose fesoterodine in elderly patients with OAB.