Randomized, placebo-controlled, multicenter trials with onabotulinumtoxinA 100U have demonstrated significant improvements in urinary incontinence (UI) and quality of life (QOL) in patients with idiopathic overactive bladder (OAB) inadequately managed by an anticholinergic.1-3 Yet, little information is available on the impact of either prior OAB duration or body mass index (BMI) on treatment effect and safety. This pooled post hoc analysis of several similarly designed placebo-controlled trials was undertaken to evaluate the efficacy and safety of onabotulinumtoxinA 100U according to baseline OAB duration and BMI in OAB patients with UI.

OAB patients were enrolled into 3 randomized, placebo-controlled, phase 3 trials and a randomized phase 4 post-marketing study, and all patients experienced ≥3 urgency UI episodes over a 3-day period and ≥8 micturitions per day. All patients were inadequately managed by an anticholinergic, and they received ≥1 onabotulinumtoxinA 100U treatment. Patients with a predominance of stress UI were excluded. In this pooled post hoc analysis, patients were stratified by baseline OAB duration (<2 [n=279], 2–5 [n=641], and >5 years [n=505]) and BMI (<25 [n=317], 25–<30 [n=454], 30–<40 [n=502], and ≥40 [n=153] kg/m2). Assessments at week 12 following a first treatment with onabotulinumtoxinA included mean change in UI episodes/day, proportions of patients with a 100% reduction in UI episodes/day (complete continence) and ≥50% reduction in UI episodes/day, mean change from baseline to week 12 in King’s Health Questionnaire (KHQ) role and social limitations domain scores, and proportions of patients who achieved/exceeded the minimally important difference (MID, 5 points) on the KHQ domains. Scores on the KHQ range from 0 to 100, with lower scores indicating better QOL. Adverse events (AEs) and the incidence/duration of clean intermittent catheterization (CIC) were recorded. Efficacy and QOL outcomes were analyzed in the intent-to-treat population (all randomized patients), and the incidence of AEs and the use and duration of CIC were analyzed in the safety population (all patients who received treatment). CIC was mandated in all of the studies if the post-void residual (PVR) urine volume was between 200 and <350 mL and the patient complained of symptoms of incomplete bladder emptying, or if PVR was ≥350 mL regardless of symptoms.

Following onabotulinumtoxinA treatment, robust reductions from baseline to week 12 in UI episodes/day were seen across all OAB duration and BMI groups (range: -2.8 to -4.2; Table). Overall, 22.9% to 38.7% of patients across all groups achieved complete continence at week 12, and most patients (range: 62.9%–72.4%) achieved a ≥50% reduction in UI episodes/day at week 12. Regardless of prior OAB duration or patient BMI, substantial improvements from baseline to week 12 were seen in KHQ role and social limitations (range: -20.6 to -27.6 and -19.1 to -25.9, respectively) that were approximately 4 to 5 times the MID (5 points). The majority of patients across all groups achieved or exceeded the MID for KHQ role and social limitations (range: 54.6%–63.4% and 54.2%–66.7%). Across all groups, the proportion of patients with CIC ranged from 2.6% to 6.1% (median duration, 64–120 days). Overall, AE rates were similar across all OAB duration and baseline BMI groups, and urinary tract infection was the most commonly reported AE.

In this large cohort of patients with OAB who were inadequately managed by an anticholinergic, a robust treatment response was observed with onabotulinumtoxinA across all OAB duration and BMI groups with no clinically meaningful difference apparent across the groups. No unexpected safety signals were observed, and the risk of CIC following onabotulinumtoxinA treatment was low regardless of prior OAB duration or patient BMI.

OnabotulinumtoxinA 100U was well tolerated with no change in CIC incidence, and was efficacious, resulting in improved QOL in OAB patients regardless of prior OAB duration or patient BMI.

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