An exploratory, placebo-controlled, dose–response study of the efficacy and safety of onabotulinumtoxinA in spinal cord injury patients with urinary incontinence due to neurogenic detrusor overactivity

Abstract

To explore the dose response to onabotulinumtoxinA 50, 100, and 200U in patients with spinal cord injury (SCI) with urinary incontinence (UI) due to neurogenic detrusor overactivity (NDO). Patients (N=73) with SCI (level T1 or lower) with NDO and UI (≥14UI episodes/week) received 30 intradetrusor injections of onabotulinumtoxinA (50U [n=19], 100U [n=21], or 200U [n=17]) or placebo (n=16) via cystoscopy, avoiding the trigone. Changes from baseline in UI episodes/week, volume voided/micturition, maximum cystometric capacity, and maximum detrusor pressure (MDP) during first involuntary detrusor contraction (IDC) were evaluated. Adverse events (AEs) were assessed. A significant linear dose response for UI episodes/week was identified at weeks 18, 30, 36, 42, and 54 (P<0.05) with a similar trend (P=0.092) at week 6 (primary time point). A significant linear dose response was observed in volume/void at all post-treatment time points up to week 54 (P<0.05) and in MDP during first IDC at week 6 (P=0.034). The proportion of patients who achieved continence at week 6 was highest in the 200U group. Duration of effect was longest with the 200U dose, compared with other treatment groups. The AEs were comparable across groups; urinary tract infection was the most common AE across all treatment groups. In this exploratory dose-response study of SCI patients with UI due to NDO, onabotulinumtoxinA 200U was the most effective dose. The AE profile was comparable across all groups.