Overactive bladder treatment using antimuscarinic drugs increases the risks for urinary tract infection (UTI) and lower urinary tract symptoms (LUTS), a new study finds.

Nobuhiro Haga, MD, PhD, of Fukuoka University in Japan, and colleagues performed a meta-analysis of 29 placebo-controlled trials of antimuscarinic agents and 9 placebo-controlled trials of beta 3-adrenoceptor agonists involving 35,939 patients with overactive bladder, published during 2002 to 2021. All trials had low risk of bias.

At 1-3 months after treatment, UTI risk was a significant 23% higher among patients receiving antimuscarinic drugs compared with placebo, the investigators reported in The Journal of Urology. The broad UTI outcome encompassed upper UTI, acute cystitis requiring treatment, as well as febrile UTI. Use of antimuscarinic drugs also was significantly associated with a 2.9-fold increased risk for urinary retention (few patients required catheterization), dysuria, and/or increased residual urine volume, factors involved in UTI pathogenesis. Antimuscarinic drugs included imidafenacin, solifenacin, tolterodine, fesoterodine, darifenacin, and trospium of various doses.

Use of beta 3-adrenoceptor agonists was not associated with any of these risks, the investigators reported. Drugs in this class included solabegron, mirabegron, and vibegron.

“To prevent urinary tract infection emergence, beta 3-adrenoceptor agonists might be safer than antimuscarinic agents,” according to Dr Haga’s team. The investigators noted that UTI causes not only LUTS, but pyelonephritis, which can lead to kidney dysfunction. They suggested that older adults and patients with diabetes might be good candidates for beta 3-adrenoceptor agonists due to their increased risks for UTI. Women with strong overactive bladder symptoms and men without bladder outlet obstruction due to benign prostatic hyperplasia or other conditions might be good candidates for antimuscarinic agents.

The investigators acknowledged that a direct comparison between antimuscarinics and beta 3-adrenoreceptor antagonists in a randomized trial would be more reliable and informative than a meta-analysis.

Reference

Tsubouchi K, Arima H, Abe M, et al. Effect of pharmacotherapy for overactive bladder on the incidence of and factors related to urinary tract infection: a systematic review and meta-analysis. J Urol. 209(4):665-674. doi:10.1097/JU.0000000000003209

Despite an increased risk of cognitive decline associated with anticholinergic medications, Black patients are 54% less likely than White patients to fill the alternative β3-agonist prescription to treat overactive bladder (OAB). Black women are 90% less likely than White women to fill a β3-agonist prescription.

The findings are from a cross-sectional analysis of the 2019 Medical Expenditure Panel Survey including 2,971,449 individuals (mean age, 66.4 years) filling prescriptions for OAB medications. The sample was nationally representative of US households. The study population was 78.3% White, 8.8% Black, 5.6% Hispanic, 2.0% Asian, and 5.3% other races.

“Given comparable efficacy among anticholinergic and β3-agonist medications for both objective and subjective disease measures, initial treatment of OAB with a β3-agonist medication is prudent,” Oluwateniola Brown, MD, of Northwestern University Feinberg School of Medicine in Chicago, Illinois, and colleagues wrote in JAMA Network Open.

Overall, 75% of patients filled anticholinergic prescriptions, 19.9% filled β3-agonist prescriptions, and 5.1% filled prescriptions for both medication classes. The median out-of-pocket cost for anticholinergics was much lower ($9.78) compared with β3-agonists ($45.00).

Dr Brown’s team adjusted analyses for income, insurance coverage, education, and potential medical contraindications, such as hypertension or preexisting cognitive impairment, but the race disparity persisted. They could not control for disease severity or prior treatment.

Dr Brown’s team emphasized that multiple guidelines discourage use of anticholinergics. The American Urologic Association advises caution in the use of anticholinergic medications to treat elderly and frail individuals with OAB. The American Geriatrics Society Beers Criteria lists anticholinergics as “potentially inappropriate” for older adults in light of interactions. The 2020 consensus update from the American Urogynecologic Society recommended avoiding anticholinergics in adults older than 70 years.

Reference

Luchristt D, Bretschneider CE, Kenton K, Simon M, Brown O. Inequities in filled overactive bladder medication prescriptions in the US. Published online May 24, 2023. JAMA Netw Open. doi:10.1001/jamanetworkopen.2023.15074

A phase 3 study evaluating the efficacy and safety of vibegron in men with overactive bladder (OAB) symptoms receiving pharmacological therapy for benign prostatic hyperplasia (BPH) met its coprimary and all secondary endpoints.  

Vibegron is an oral, small molecule beta-3 adrenergic receptor agonist. The multicenter, randomized, double-blind, URO-901-3005 study (ClinicalTrials.gov Identifier: NCT03902080) included 1105 men with OAB symptoms receiving pharmacological therapy for BPH (eg, alpha blocker monotherapy or alpha blocker in combination with 5 alpha reductase inhibitor). Study participants were randomly assigned to receive vibegron 75mg orally once daily or placebo for 24 weeks. 

Results showed that treatment with vibegron met the coprimary endpoints demonstrating statistically significant reductions from baseline in daily micturitions (-2.04 [SE: 0.109]; P <.0001) and in daily urgency episodes (-2.88 [SE: 0.164]; P <.0001) at week 12 vs placebo (-1.30 [SE: 0.109] and -1.93 [SE: 0.164], respectively). 

Additionally, statistically significant reductions were observed with vibegron in key secondary endpoints vs placebo, including the average number of nocturia episodes per night (-0.88 vs -0.66, respectively; P =.0015); the average number of urge urinary incontinence episodes per day (-2.19 vs -1.39, respectively; P =.0034); and the International Prostate Symptoms Storage score (-3.0 vs -2.1, respectively; P =.0001). 

Vibegron was also associated with a statistically significant increase in the average volume voided per micturition (25.63mL) compared with placebo (10.56mL; P <.0001). No new safety signals were reported in the trial.

Patients who completed the URO-901-3005 were eligible to continue to the open-label URO-901-3006 extension-study (ClinicalTrials.gov Identifier: NCT04103450). Results showed all endpoints were maintained up to 52 weeks.

“We are pleased to share the results of this study, which underscores the promise of one of our key marketed assets beyond its initial approved indication,” said Myrtle Potter, President and Chief Executive Officer of SMPA. “With these positive data, we look forward to exploring the potential of vibegron as an option for men experiencing OAB symptoms and BPH.”

Vibegron is currently marketed under the brand name Gemtesa for the treatment of OAB with symptoms of urge urinary incontinence, urgency, and urinary frequency in adults.