Safety and Efficacy of Mirabegron Compared to Antimuscarinics in Older Subjects with Overactive Bladder
Introduction
Anticholinergic medications have been widely prescribed for a respiratory diseases, gastrointestinal disorders, allergies, neurological conditions and overactive bladder (OAB) in older population. Cumulative exposure to one or more anticholinergic medications termed as "anticholinergic burden" is directly associated with an increased risk of adverse effects (AEs) outcomes, particularly among older individuals. Mirabegron, an oral selective ?3-adrenergic receptor agonist, has demonstrated similar efficacy to antimuscarinics with a more favorable safety profile in OAB, without contributing to anticholinergic burden. However, there is lack of clarity on the degree to which the favorable safety profile relative to antimuscarinics is affected by high anticholinergic burden in older individuals.
Aim
- This meta-analysis compares the safety and efficacy profile of mirabegron relative to antimuscarinics in older adults with OAB.
Method
Study Design
- Systematic literature review (SLR) and network meta-analysis (NMA) of randomized controlled trials (RCTs)
Inclusion Criteria
- RCTs in which at least 80% of the participants were aged >65 years old
Treatment Strategy
- SLR was conducted using MEDLINE, EMBASE and PubMed databases
- NMA was conducted to synthesize the identified safety and efficacy parameters associated with mirabegron and antimuscarinic use
- Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines in designing, performing, and reporting the literature review were followed.
- In line with current best practices, the NMA was conducted using a Bayesian approach and according to the overall general guidance for evidence synthesis developed by the National Institute for Health and Care Excellence decision support unit.
- Estimates of relative safety and relative efficacy were evaluated via the odds ratio (OR) and means and credible intervals respectively.
Endpoints
- Safety endpoints
- Urinary retention
- Dry mouth
- Constipation
- Treatment-emergent adverse events (TEAEs)
- Treatment related treatment discontinuation
- Efficacy endpoints
- Incontinence episodes per 24 hrs
- Urgency incontinence episodes per 24 hrs
- Micturitions per 24 hrs
- Volume voided per micturition
- Urgency episodes per 24 hrs
Results
- A total of 3078 abstracts, 300 of which underwent full-text screening, were identified using the search criteria.
- Twenty articles reporting on 21 randomized controlled trials were eligible for data extraction and synthesis.
- Twelve studies contributed to the safety results
- The safety analysis revealed that mirabegron was not associated with an increased odds of dry mouth (OR 0.76) or constipation (1.08) relative to placebo, whereas antimuscarinics were strongly associated with these events (OR range 3.78-7.85 and 2.12-4.66, respectively).
- Mirabegron was associated with similar odds of experiencing adverse event-related treatment discontinuations relative to placebo (0.9), while the odds of experiencing an adverse event-related treatment discontinuation for antimuscarinics had a range of 1.14-3.03 (in most cases, the association was mild).
- Neither mirabegron nor antimuscarinics were strongly associated with increased odds of experiencing overall TEAEs (OR range 1.25-1.55), apart from fesoterodine (2.2).
- Thirteen studies contributed to the efficacy results
- The efficacy endpoints were comparable between mirabegron and antimuscarinics in this older population.
Conclusion
- The efficacy of mirabegron was similar to that of antimuscarinics among older adults with overactive bladder.
- Mirabegron had a favorable safety profile and the safety outcomes typically associated with anticholinergic burden, were less frequently observed in patients treated with mirabegron.
Drugs Aging. 2020 Nov;37(11):801-816. Doi: 10.1007/s40266-020-00792-9.
