A Randomized Controlled Trial Evaluating Three Active Doses of OnabotulinumtoxinA for the Treatment of Neurogenic Detrusor Overactivity in Children
Paul F. Austin, MD1, Israel Franco, MD2, Eric Dobremez, MD, PhD3, Pawel Kroll, MD, PhD4, Wilson Titanji, PhD5, Till Geib, PhD5, Brenda Jenkins, BS5, Piet Hoebeke, MD6.
1Texas Children's Hospital, Houston, TX, USA, 2Yale New Haven Children's Hospital, New Haven, CT, USA, 3Hôpital Pellegrin Enfants, Bordeaux, France, 4Paediatric Urology Clinic and Neuro-urology Unit, Poznań, Poland, 5Allergan plc, Irvine, CA, USA, 6Ghent University Hospital, Ghent, Belgium.
Background: Urinary incontinence (UI) due to neurogenic detrusor overactivity (NDO) significantly affects quality of life. OnabotulinumtoxinA (onabotA) 200U is an approved treatment for NDO in adults. This study evaluated the efficacy and safety of onabotA detrusor injection in children with NDO not adequately managed with anticholinergic therapy.
Methods: This was a multicenter, randomized, double-blind study (maximum duration 48 weeks) in children (≥5 to ≤17 years) with UI due to NDO caused by spinal dysraphism (n=99), spinal cord injury (n=13) or transverse myelitis (n=1). Clean intermittent catheterization use was mandatory. Patients received a single treatment of onabotA (50U, 100U or 200U; not to exceed 6 U/kg) delivered as 20 injections of 0.5 mL excluding the trigone. Patients could request retreatment after week 12. Those completing the study could enter an extension study.
Results: Improvements in daytime UI were observed in all dose groups with adjusted mean reductions from baseline (BL) at week 6 (primary timepoint) of 1.30 episodes/day for 50U and 100U and 1.34 episodes/day for 200U (BL: 50U, 2.81; 100U, 2.99; 200U, 3.68). At least 75% of patients in each group reported 'great improvement' or 'improvement' on the Treatment Benefit Scale at week 6. The adjusted mean change from BL at week 6 in urine volume at first morning catheterization was 21.9, 34.9, and 87.5 mL in the 50U, 100U and 200U groups (BL: 203.5, 164.2, 187.7 mL); p=.006 for 200U vs 50U. There was a dose-dependent reduction in maximum detrusor pressure during the storage phase; adjusted mean reductions from BL were 12.9, 20.1 and 27.3 cmH2O in the 50U, 100U and 200U groups (BL: 58.2, 56.5, 56.7 cmH2O); p=.02 for 200U vs 50U. Median time to request for retreatment was 30.6, 24.1 and 29.6 weeks in the 50U, 100U and 200U groups. The safety profile was similar across doses. Overall, treatment emergent adverse events were reported in 71.1%, 73.3% and 76.7% of patients, respectively; urinary tract infection was most common (50U, 18.4%; 100U, 28.9%; 200U, 6.7% within the first 12 weeks of treatment).
Conclusions: All three doses of onabotA were well tolerated and demonstrated clinical efficacy for treatment of daytime UI in children with NDO not adequately managed with anticholinergic therapy. However, the 200U dose showed clinically and statistically greater improvements vs 50U in the important efficacy measures of maximum detrusor pressure during storage and volume at first morning catheterization.
Source of Funding: Allergan plc.
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