OnabotulinumtoxinA Approved for Pediatric Neurogenic Detrusor Overactivity

Paul F. Austin, MD, FAAP

The FDA has approved onabotulinumtoxinA (Botox; Allergan/AbbVie) for the treatment of neurogenic detrusor overactivity (NDO) in pediatric patients aged 5 years or older that are intolerant of or do not respond well to anticholinergic medication.¹

OnabotulinumtoxinA was evaluated for the treatment of pediatric NDO in a randomized, double-blind, phase 3 study (NCT01852045) in more than 100 patients as well as a long-term extension study. Data showed that intradetrusor administration of onabotulinumtoxinA reduced daytime urinary incontinence episodes, lowered maximum bladder pressure, and increased bladder capacity at week 6. 

The agent was originally approved for the treatment of adult NDO in 2011.² The causes of NDO in children can include transverse myelitis, spinal cord injury, spina bifida, and multiple sclerosis. 

"Many children with underlying neurologic conditions may experience bladder and kidney damage over time, which underscores the importance of treatment. When caring for pediatric patients with neurogenic detrusor overactivity, we strive to reduce bladder pressure and increase the bladder's capacity. Previously, treatment options were limited primarily to anticholinergic medicines, where long-term use needs to be considered carefully, in addition to surgery," said Paul F. Austin, MD, FAAP, chief, pediatric urology, Texas Children's Hospital and professor, urology, Baylor College of Medicine, in a statement.

"Effectively managing neurogenic detrusor overactivity requires ongoing care, and there has been a high unmet need for alternative treatments. With its proven safety and efficacy profile, Botox offers a new treatment option for pediatric patients who are not adequately managed by anticholinergics,” he added.

READ MORE: Botox Gains FDA Approval for Lower Limb Spasticity in Pediatric Patients

Researchers evaluated 114 participants with an average age of 11.3 years (standard deviation [SD], 3.29), 113 of which received treatment. These patients were randomized to be treated with either 50 (n = 38), 100 (n = 45), or 200 (n = 30) units (U) of onabotulinumtoxinA, not exceeding more than 6 U per kg.³ 

Researchers found that the patients treated with 50 U had a change from baseline of daytime incontinent episodes of a least squares mean (LSM) of -1.30 (SD, 0.205), patients treated with 100 U had an LSM of -1.30 (SD, 0.189), and patients treated with 200 U a -1.34 (SD, 0.245) LSM. There were no significant differences in incontinent episodes between dosage groups. 

Researchers also evaluated change from baseline in average urine volume at first morning catheterization, in which a positive change from baseline indicates improvement. Patients in the 50 U group had an LSM of 21.93 (SD, 14.676), patients in the 100 U an LSM of 34.90 (SD, 13.580), and patients in the 200 U 87.49 (SD, 17.808). A significant difference was seen between the 50 U and 200 U groups (P = .0055).

Other secondary outcomes measured included change from baseline in maximum cystometric capacity, percentage of participants with nighttime urinary incontinence, percentage of participants with involuntary detrusor contractions (IDC), change from baseline in maximum detrusor pressure during the first IDC in participants with IDC, change from baseline in maximum detrusor pressure during the storage phase, and change from baseline in detrusor leak point pressure (DLPP) during the storage phase. 

Treatment-emergent adverse events (TEAEs) were reported by 27 (71.1%) patients in the 50 U group, 33 (73.3%) in the 100 U group, and 23 (76.7%) in the 200 U group.

"Botox is the first neurotoxin approved for use in treating neurogenic detrusor overactivity in children who are not adequately managed with anticholinergic medication. While always satisfying to bring forth new indications, it is particularly rewarding when we can help advance care for pediatric patients with Botox," added Mitchell F. Brin, MD, senior vice president and chief scientific officer, Botox & neurotoxins, AbbVie, to the statement.

REFERENCES

1. BOTOX® (onabotulinumtoxinA) receives FDA approval for pediatric detrusor overactivity associated with a neurologic condition. News release. Allergan. Published online February 10, 2021. Accessed February 10, 2021. https://www.prnewswire.com/news-releases/botox-onabotulinumtoxina-receives-fda-approval-for-pediatric-detrusor-overactivity-associated-with-a-neurologic-condition-301225563.html
2. Botox® approved for urinary incontinence. News release. Allergan. Published online August 26, 2011. Accessed February 10, 2021. https://mymsaa.org/news/botox-approved-for-urinary-incontinence
3. Study of OnabotulinumtoxinA (BOTOX®) for urinary incontinence due to neurogenic detrusor overactivity in pediatric patients. NIH US National Library of Medicine. Published online November 21, 2019. Accessed February 10, 2021. https://clinicaltrials.gov/ct2/show/results/NCT01852045