Effect of mirabegron on cognitive function in elderly patients with overactive bladder: MoCA results from a phase 4 randomized, placebo-controlled study (PILLAR)

Abstract

Background: Antimuscarinics are often used for treatment of overactive bladder (OAB), but exposure to medications such as antimuscarinics that have anticholinergic properties has been linked to adverse cognitive effects. A phase 4 placebocontrolled study (PILLAR; NCT02216214) described the efficacy and safety of mirabegron, a β 3 -adrenoreceptor agonist, for treatment of wet OAB in patients aged ≥65 years. This pre-planned analysis aimed to measure differences in cognitive function between mirabegron and placebo, using a rapid screening instrument for mild cognitive impairment: the Montreal Cognitive Assessment (MoCA).Methods: Outpatients aged ≥65 years with wet OAB were randomized 1:1 to mirabegron or placebo, stratified by age (<75/≥75 years). There were no exclusion criteria regarding cognitive status. Patients randomized to mirabegron initially received 25 mg/day with an optional increase to 50 mg/day after week 4/8 based on patient/investigator discretion. The MoCA was administered at baseline and end of treatment (EoT, week 12). The study protocol was Independent Ethics Committee/Institutional Review Board-approved.Results: Of the 887 randomized patients who received ≥1 dose of study drug, 72.3% were female, 79.5% were white, and 28.1% were aged ≥75 years. All patients had ≥1 comorbidity and 94.3% were receiving ≥1 concomitant medication. One third of patients had a history of psychiatric disorders, the most common being depression (17.2%), insomnia (15.7%), and anxiety (11.4%). Baseline mean (standard error, SE) MoCA total scores were 26.9 (0.1) and 26.8 (0.1) in the mirabegron and placebo groups, respectively. Among patients with MoCA data available at baseline/EoT, 27.1% (115/425) and 25.8% (106/411) of mirabegron and placebo group patients, respectively, had impaired cognitive function at baseline (MoCA total score <26). There was no statistically significant change in adjusted mean (SE) MoCA total score from baseline to EoT in the mirabegron group (−0.2 [0.1]) or the placebo group (−0.1 [0.1]).Conclusions: Treatment with mirabegron for 12 weeks did not contribute to drug-related cognitive side effects in patients aged ≥65 years, as measured by the MoCA. Furthermore, the pattern of change in cognition over time in an older OAB trial population does not appear to differ from that of subjects receiving placebo.

Safety and Tolerability Results from the PILLAR Study: A Phase IV, Double-Blind, Randomized, Placebo-Controlled Study of Mirabegron in Patients ≥ 65 years with Overactive Bladder-Wet

“…TEAEs were assessed overall and in each age subgroup (< 75 and ≥ 75 years). TEAEs of special interest included cardiovascular events, blood pressure, myocardial infarction, stroke, serious arrhythmias, urinary tract infection (UTI), acute urinary retention, benign prostatic obstruction (BPO) requiring surgery, and cognitive impairment as determined by the Montreal Cognitive Assessment score (results presented in a separate manuscript [22]). Cardiovascular events were assessed by an independent adjudication committee.…”

Relationship between Lower Urinary Tract Dysfunction and Dementia

“…Treatment with mirabegron over 12 weeks had no adverse impact on cognitive function in older patients at risk of or concerned with cognitive impairment, based on the Montreal Cognitive Assessment. 32 Therefore, mirabegron is increasingly being used as an alternative, especially to anticholinergic treatment in elderly patients. 5 …”

Recent advances in managing overactive bladder

“…The authors argue that combination therapy may be better for the elderly rather than solifenacin 10 mg, as the latter may increase the anticholinergic load. Another study found that there was no significant change in the Montreal Cognitive Assessment from baseline to week 12 in elderly patients using mirabegron 16 .…”