Mirabegron effective for paediatric NDO patients

The β3-adrenoreceptor agonist mirabegron – a proven effective treatment for overactive bladder and neurogenic detrusor overactivity (NDO) in adults – was equally as effective in children and adolescents with NDO, a phase III study suggests.

Left untreated, NDO may lead to upper urinary tract deterioration and bladder compliance reduction. [Paraplegia 1995;33:326-329] “A main objective of treatment is to maintain low bladder pressure during bladder storage and voiding and therefore avoid associated complications such as urinary tract infections (UTIs), bladder stones, fibrosis, trabeculation, and autonomic dysreflexia,” said the researchers.

NDO is successfully managed with CIC* and the antimuscarinic oxybutynin, the current standard pharmacologic treatment for NDO. [Pediatr Nephrol 2008;23:717-725] However, antimuscarinics are tied to anticholinergic adverse events (AEs) which may limit adherence, said the researchers. “[In paediatric patients, of particular concern] is the potential for impairment of cognitive development and learning, especially as anticholinergic central nervous system AEs are reportedly more common in paediatric [vs adult] patients.”

Fifty-five children and 31 adolescents (mean age 10.1 years, 45 percent male) received mirabegron** QD at an equivalent adult dose of 25 mg. The dose was increased to 50 mg if 25 mg was insufficient or if safety/tolerability concerns arose. [Neurourol Urodyn 2021;40:1490-1499]

Week 24 saw a significant increase in maximum cystometric capacity (MCC) from baseline in the overall cohort (87.20 mL; p<0.001) and in both age groups (p<0.001). “The increase in MCC was apparent from week 4 in both children and adolescents and overall … [and] were sustained across the 24-week treatment period,” said the researchers.

Using the CGI-C***, most participants rated their condition as either much (48 percent) or very much improved (25 percent). Although 17 percent reported only minimal improvement, none indicated that their condition was much worse/very much worse.

About 60 percent reported treatment-emergent AEs (TEAEs), the most common being UTI (23 percent) and nasopharyngitis and pyrexia (6 percent each). Mirabegron was generally well-tolerated, with a profile correlating with that seen in adults. “As mirabegron has a distinct mechanism of action, and is generally devoid of antimuscarinic AEs, it generally has a favourable safety profile,” said the researchers.

Secondary urodynamic parameters

In the overall cohort, there were also significant increases across most urodynamic and leakage parameters, ie, mean bladder compliance (14.22 mL/cm H₂O), bladder volume until first detrusor contraction (104.02 mL), maximum catheterized volume per catheterization (62.28 mL), and number of dry days (leakage-free) per week (1.65 days; p<0.05 for all). Results were consistent even when stratifying by age groups.

The increased bladder filling volume ties with increased bladder compliance, implying that the MCC improvements may have been driven by the increased bladder compliance, the researchers noted.

“[U]rodynamic assessment in children is a challenging endeavour. In younger patients, excellent ‘negotiation’ skills are required from the physician to get a compliant child during the examination,” the researchers pointed out. “[Nonetheless,] the MCC increases were consistent with the increase in maximum catheterized daytime volume recorded in the outpatient setting, thereby supporting the relevance of urodynamic assessments to ‘real-world’ settings.”

And although adherence may be less of a concern in a younger patient cohort, most participants rated the tablets and oral solution as good in terms of smell, taste, and swallow acceptability. “[This] is reassuring,” they said. Also, despite the absence of a placebo arm, most endpoints were objective urodynamic parameters, which were less prone to bias.