ß3-adrenergic receptor agonists (ß3 agonists) have been used in treatment of overactive bladder (OAB) and neurogenic detrusor overactivity (NDO) in adults. However, its use in children has only recently been approved by Food and Drug Administration for patients with NDO. As in adults, the role of ß3 agonists in children may include conditions such as OAB. This systematic review and meta-analysis aim to understand the intended use, efficacy, and safety of ß3 agonists in pediatric population.
A literature search was performed in February 2021 across Medline, EMBASE, Scopus, Cochrane Library, and ClinicalTrials.gov. No language restrictions were placed. All records describing the clinical use of ß3 agonists in pediatric patients (<18 years of age) were included, regardless of the methodological design or outcomes assessed. The identified records were screened based by two independent authors. The reporting was compliant with the PRISMA statement. Data extraction was performed by two independent reviewers, blinded to each other's' extractions. The data was pooled using the fixed effects model.
Of 367 records identified, 8 studies were included in the review (3 prospective, 5 retrospective). ß3 agonists led to improvements in both UDS parameters and self-reported outcomes such as incontinence. Commonly reported side effects were headaches (3%-5.9%), constipation (3.5%-5.7%), rhinitis/nasopharyngitis (1.7%-5.8%), and blurred vision (1.7%-2.9%). Clinically meaningful changes in safety outcomes (blood pressure, heart rate, ECG-related changes, liver function) were rare. Pre- and post-ß3 agonist use, pooled effect estimates for maximum cystometric capacity for 171 patients was mean difference of+98.84 mL (95% CI 74.72, 122.96); for complete dryness, assessment of 235 patients showed a peto odds ratio of 8.68 (95% CI 5.22, 14.45).
ß3 agonists appear to be a promising, effective, and safe alternative/adjunctive therapy in management of pediatric NDO or overactive bladder, with improvements in both objective UDS parameters and subjective patient reported outcomes following their use.
The Journal of urology. 2021 Dec 01 [Epub ahead of print]
Jin K Kim, Mark Jason De Jesus, Min Joon Lee, Joana Dos Santos, Jun S Dy, Jessica M Ming, Mandy Rickard, Armando J Lorenzo, Michael E Chua
Division of Urology, Department of Surgery, The Hospital for Sick Children, Toronto, ON, Canada., Institute of Urology, St. Luke's Medical Center, Quezon City, Philippines., Division of Urology, Department of Surgery, University of Toronto, Toronto, ON, Canada., Division of Urology, Department of Surgery, University of New Mexico, Albuquerque, New Mexico, USA.