Pediatric lower urinary tract dysfunction (LUTD) is a common condition that affects around 15%-20% of children.¹ It is characterized by various symptoms, including urgency, frequency, voiding difficulties, and incontinence. Managing pediatric LUTD can be challenging and may involve different approaches such as behavioral modifications, biofeedback, medication, and surgery.² Anticholinergics are currently widely used to manage pediatric LUTD; however, they are being reconsidered due to their potential side effects, such as cognitive impairment, constipation, and dry mouth.³ β3-adrenergic receptor agonists such as mirabegron and vibegron are being investigated as a potential alternative for pediatric LUTD management.⁴

β3-agonists work by relaxing the detrusor muscle in the bladder. Postulated mechanisms of action include prejunctional suppression of acetylcholine release from the parasympathetic nerves during the storage phase and inhibition of microcontractions through β3-adrenoceptors on detrusor smooth muscle cells or suburothelial interstitial cells.⁵ These drugs have shown a favorable safety profile compared to anticholinergics, but further research is necessary to establish their long-term safety in pediatric patients. Although some evidence suggests that β3-agonists may be effective in managing pediatric LUTD, current guidelines have not stated any recommendations for their routine use in pediatric patients due to limited clinical evidence (unpublished data).⁶

The U.S. Food and Drug Administration approved the application for vibegron for the treatment of adult overactive bladder (OAB) in 2019. However, the safety and efficacy in the pediatric population remained unclear.⁷ In contrast, mirabegron was approved for treating adult OAB in 2012, and for pediatric neurogenic detrusor overactivity in 2021.⁸ The approval was based on the results of an open-label phase 3 trial by Baka-Ostrowska et al, which found that after 24 weeks of treatment mirabegron was associated with significant improvements in maximum cystometric capacity, number of detrusor contractions, the volume of urine held until first detrusor contraction, and number of daily urine leakage episodes.^8,9 The trial also demonstrated that the drug was generally well tolerated in pediatric patients, providing additional support for the potential benefits of β3-agonists in this population.⁹

A recent systematic review and meta-analysis by Kim et al in 2022 included 8 studies (3 prospective and 5 retrospective) that found β3-agonists were associated with improvements in urodynamics parameters and self-reported outcomes such as incontinence.¹⁰ Although studies suggest that β3-agonists such as mirabegron may be effective in managing pediatric LUTD, further high-quality studies are required to establish their safety and efficacy, and the optimal dosing strategies and patient selection for β3-agonists in pediatric LUTD remain to be identified.¹⁰ Recent network meta-analyses comparing vibegron and mirabegron in the management of adult OAB have shown that vibegron was associated with significantly greater improvement in daily total urinary incontinence episodes at 52 weeks than mirabegron and tolterodine, while vibegron was also more efficacious than mirabegron in reducing mean voided volume/micturition (95% CI 5.15, 14.98). Safety outcomes for vibegron and mirabegron were similar to those in the placebo group, except for mirabegron, which had a higher risk of nasopharyngitis and cardiovascular adverse events than the placebo.^11,12 Some recent reports on the use of vibegron in the pediatric population have shown effectiveness in refractory daytime urinary incontinence and idiopathic OAB for improving both subjective symptoms and lower urinary tract function.^13,14 Currently, a multi-institutional clinical trial on vibegron is underway to assess its effect on the management of pediatric neurogenic LUTD.¹⁵

The management of pediatric LUTD is a complex process that involves a thorough evaluation of the patient’s symptoms, medical history, and physical examination. Behavioral modifications such as bladder retraining and pelvic floor muscle exercises are often the first-line approach for children with LUTD.³ However, in some cases, pharmacological interventions, including β3-agonists, may be necessary to manage the symptoms effectively.¹¹ While β3-agonists show promise as a potential treatment option for pediatric LUTD, their use should be carefully considered on a case-by-case basis due to limited evidence and potential side effects. It is also crucial to monitor the initial response and the effect of β3-agonists on blood pressure, including the common side effects of urinary tract infection, nasopharyngitis, and headache.^8,9