Safety and efficacy of vibegron in pediatric patients with treatment-resistant nocturnal enuresis: a multicenter retrospective study.

Background: Nocturnal enuresis (NE) is a common chronic condition in children. Although enuresis alarms and desmopressin are the first-line treatments recommended by clinical guidelines, 20-40% of affected children demonstrate inadequate response and require additional therapeutic interventions. β3-adrenoceptor agonists are emerging as promising alternatives to anticholinergics, offering a more favorable safety profile with a lower incidence of common side effects. This multicenter retrospective study aimed to evaluate the safety and effectiveness of vibegron in children with treatment-resistant NE (TR-NE) and compare different treatment strategies. Methods: This retrospective observational study was conducted at 12 hospitals affiliated with the Japanese Society on Enuresis and Incontinence. It enrolled children aged 5-18 years who received vibegron (50 mg once daily) for refractory NE between November 2018 and December 2021. The median treatment duration was 245 (interquartile range, 126-484) days. The primary outcome was treatment efficacy, assessed by the change in the number of wet nights over 30 days from baseline to 1 month. Safety was evaluated by monitoring adverse events. Treatment response was defined using the International Children's Continence Society criteria. Patients were classified into an "add-on" group (vibegron combined with existing therapy) or a "switch" group (transitioned from prior anticholinergics to vibegron). Results: Of the 387 children enrolled, 386 were included for safety analysis and 369 for efficacy evaluation. Four patients (1.0%) experienced mild adverse events that led to the discontinuation of vibegron, and all resolved promptly. Overall, 52.8% achieved a partial or complete response (CR) (≥50% reduction in wet nights), and 17.3% achieved a CR. The add-on group showed significantly greater improvements than the switch group (56.9% Conclusions: Vibegron is a safe and effective option for pediatric patients with TR-NE. Add-on strategies-particularly triple therapy-were more effective than monotherapy switching, strengthening the incorporation of vibegron as part of multimodal treatment strategies. Given the retrospective nature of the study, prospective randomized trials are warranted to confirm these findings and optimize the treatment protocols.