Adverse Event Assessment of Antimuscarinics for Treating Overactive Bladder: A Network Meta-Analytic Approach

Abstract

BackgroundOveractive bladder (OAB) affects the lives of millions of people worldwide and antimuscarinics are the pharmacological treatment of choice. Meta-analyses of all currently used antimuscarinics for treating OAB found similar efficacy, making the choice dependent on their adverse event profiles. However, conventional meta-analyses often fail to quantify and compare adverse events across different drugs, dosages, formulations, and routes of administration. In addition, the assessment of the broad variety of adverse events is dissatisfying. Our aim was to compare adverse events of antimuscarinics using a network meta-analytic approach that overcomes shortcomings of conventional analyses.MethodsCochrane Incontinence Group Specialized Trials Register, previous systematic reviews, conference abstracts, book chapters, and reference lists of relevant articles were searched. Eligible studies included randomized controlled trials comparing at least one antimuscarinic for treating OAB with placebo or with another antimuscarinic, and adverse events as outcome measures. Two authors independently extracted data. A network meta-analytic approach was applied allowing for joint assessment of all adverse events of all currently used antimuscarinics while fully maintaining randomization.Results69 trials enrolling 26′229 patients were included. Similar overall adverse event profiles were found for darifenacin, fesoterodine, transdermal oxybutynin, propiverine, solifenacin, tolterodine, and trospium chloride but not for oxybutynin orally administered when currently used starting dosages were compared.ConclusionsThe proposed generally applicable transparent network meta-analytic approach summarizes adverse events in an easy to grasp way allowing straightforward benchmarking of antimuscarinics for treating OAB in clinical practice. Most currently used antimuscarinics seem to be equivalent first choice drugs to start the treatment of OAB except for oral oxybutynin dosages of ≥10 mg/d which may have more unfavorable adverse event profiles.

Neurogenic detrusor overactivity in adults: a review on efficacy, tolerability and safety of oral antimuscarinics

“…This is in accordance with the Guidelines of the European Association of Urology on NLUTD, stating that 'neurogenic patients usually need a higher dose of AM agents than patients with IDO (LE 1b).' 4 In regards to tolerability and safety, the study results demonstrate that oxybutynin IR has the highest dry mouth rate compared with all other AM (Tables 3a and 3b), which is in accordance with the results given in the meta-analyses by Chapple et al 1 and Kessler et al 40 in patients with IDO/OAB. Although many neurogenic Table 3a Placebo-controlled studies-tolerability and safety outcomes a Sto¨hrer et al 13 Sto¨hrer et al 15 Sto¨hrer et al 14 Ethans et al 16 Oxy Table 3b Active-controlled studies-tolerability and safety outcomes a…”

Initial experience with the treatment of neurogenic detrusor overactivity with a new β-3 agonist (mirabegron) in patients with spinal cord injury

“…4 Nevertheless, treatment with antimuscarinic drugs is frequently discontinued due to side effects (dry mouth and constipation) or a lack of efficacy. 5 In particular in patients with SCI, who suffer from a neurogenic bowel dysfunction, the concomitant antmiuscarinic treatment will worsen the constipation. Therefore there is a need for therapy alternatives.…”

The overactive bladder: where are we in 2016?

“…There is very little high-quality evidence of a difference between agents in terms of these sideeffects, with only oxybutynin 10mg conferring a significantly increased risk. 10 An analysis of UK prescription data found that the proportion of patients still on their originally prescribed agent at 12 months ranged from 14-35% for different agents in common use. 11 This poor persistence rate is due to a combination of side-effects and lack of perceived efficacy.…”