OnabotulinumtoxinA for the treatment of neurogenic detrusor overactivity in children

Abstract

This study evaluated whether one (or more) of three doses of onabo-tulinumtoxinA were safe and effective to treat neurogenic detrusor overactivity (NDO) in children. Methods: This was a 48-week prospective, multicenter, randomized, doubleblind study in children (aged 5-17 years) with NDO and urinary incontinence (UI) receiving one onabotulinumtoxinA treatment (50, 100, or 200 U; not to exceed 6 U/kg). Primary endpoint: change from baseline in daytime UI episodes. Secondary endpoints: change from baseline in urine volume at first morning catheterization, urodynamic measures, and positive response on the treatment benefit scale. Safety was also assessed. Results: There was a similar reduction in urinary incontinence from baseline to Week 6 for all doses (−1.3 episodes/day). Most patients reported positive responses on the treatment benefit scale (75.0%−80.5%). From baseline to Week 6, increases were observed in urine volume at first morning clean intermittent catheterization (50 U, 21.9 ml; 100 U, 34.9 ml; 200 U, 87.5 ml; p = 0.0055, 200 U vs. 50 U) and in maximum cystometric capacity (range 48.6−63.6 ml) and decreases in maximum detrusor pressure during the storage phase (50 U, −12.9; 100 U, −20.1; 200 U, −27.3 cmH 2 O; p = 0.0157, 200 U vs. 50 U). The proportion of patients experiencing involuntary detrusor contractions dropped from baseline (50 U, 94.4%; 100 U, 88.1%; 200 U, 92.6%) to Week 6 (50 U, 61.8%; 100 U, 44.7%; 200 U, 46.4%). Safety was similar across doses; urinary tract infection was most frequent. Conclusions: OnabotulinumtoxinA was well tolerated and effective for the treatment of NDO in children; 200 U showed greater efficacy in reducing bladder pressure and increasing bladder capacity.

Onabotulinumtoxin A (Botox): A reasonable alternative for refractory neurogenic bladder dysfunction in children and young adults

“…Our finding of a significant improvement over the entire cohort regarding capacity and compliance is congruent with larger series which randomized children with neurogenic bladder to either 50, 100, or 200 U of Botox, and showed a dose‐dependent decrease in Pdetmax and bladder capacity 5 . In patients presenting with a high‐pressure bladder (Pdetmax > 20) with known risk of upper urinary tract deterioration, our data reveals this subgroup significantly improves their compliance and capacity.…”

“…4 Botox, as a next-step therapeutic agent, helps improve these urodynamic parameters by improving capacity, compliance, end-fill maximum detrusor pressure (Pdetmax) and neurogenic detrusor overactivity (NDO). [5][6][7] While Botox may offset or delay the need for augmentation enterocystoplasty, 8 we must acknowledge that not all patients respond favorably to Botox injections.…”

“…Urodynamic testing in the pediatric NGB population is the standard of care to detect urinary tract compromise, such as decreased capacity, diminished compliance, or elevated leak point pressures (LPP), 3 that occurs even when patients are managed with CIC and oral agents 4 . Botox, as a next‐step therapeutic agent, helps improve these urodynamic parameters by improving capacity, compliance, end‐fill maximum detrusor pressure (Pdetmax) and neurogenic detrusor overactivity (NDO) 5–7 . While Botox may offset or delay the need for augmentation enterocystoplasty, 8 we must acknowledge that not all patients respond favorably to Botox injections.…”

Clinical Application of Botulinum Neurotoxin in Lower-Urinary-Tract Diseases and Dysfunctions: Where Are We Now and What More Can We Do?

“…A high rate of urinary continence can be achieved, with improvements in urodynamic parameters, including a reduction in detrusor pressure to <40 cmH 2 O and an increase in compliance to >20 mL/cmH 2 O, without major adverse events. In children with NDO, a dose of 200 U of Botox was well tolerated and showed greater efficacy in bladder pressure reduction and bladder capacity increase [ 94 ]. Children with a high detrusor pressure and low bladder compliance had a significantly greater improvement in compliance after detrusor Botox injections [ 95 ].…”

Lower urinary tract dysfunction in pediatrics progress to kidney disease in adolescents: Toward precision medicine in treatment

“…Onabotulinum toxin A showed positive efficacy and safety in children at doses up to 360 U. It was shown that 32%–100% of children achieved continence, detrusor pressure was reduced by 32% to 54%, and the maximum pressure was below the 40 cm H 2 O threshold[ 46 ].…”