Randomized, placebo-controlled, multicenter trials with onabotulinumtoxinA 100U have demonstrated significant improvements in urinary incontinence (UI) and quality of life (QOL) in idiopathic overactive bladder (OAB) patients who were inadequately managed by an anticholinergic [1,2]. Incomplete bladder emptying resulting in the need for clean intermittent catheterization (CIC) is known to occasionally occur in OAB patients who have been treated with onabotulinumtoxinA. However, the incidence of CIC in OAB patients following retreatment with onabotulinumtoxinA requires further characterization. This post hoc analysis of several pooled placebo-controlled trials was undertaken to evaluate the risk of CIC as well as treatment response and QOL outcomes following reinjection with onabotulinumtoxinA 100U.

Patients with OAB who had experienced ≥3 urgency UI episodes over a 3-day period and ≥8 micturitions per day were enrolled from 3 phase 3 trials and a post-marketing study, all of similar design. All patients were inadequately managed by an anticholinergic. Patients could request and receive retreatment with open-label onabotulinumtoxinA ≥12 weeks after the previous treatment if they met the following criteria: ≥2 urgency UI episodes and ≤1 urgency UI–free day in a 3-day bladder diary in the week prior to qualification. CIC was mandated in all of the studies if the post-void residual (PVR) urine volume was 200 to <350 mL and the patient had associated symptoms determined by the investigator to require CIC or if PVR was ≥350 mL regardless of symptoms. The incidence of CIC was evaluated over 12 weeks following treatments 1 and 2. The mean change from baseline in UI episodes/day, proportions of patients with 100% reduction in UI episodes/day (ie, complete continence) and ≥50% reduction in UI episodes/day, mean changes from baseline in King’s Health Questionnaire (KHQ) role (RL) and social limitations (SL) domains, and proportions of patients with improvements on the Treatment Benefit Scale (TBS) were assessed at week 12 after treatments 1 and 2. Adverse events were recorded over 12 weeks following treatments 1 and 2.

CIC rates in the first 12 weeks following the first treatment were 6.2% (51/825) with onabotulinumtoxinA and 0.3% (2/727) with placebo (median duration, 85 and 10 days, respectively). In the 12 weeks after the second treatment, CIC rates were 5.5% (26/469) for patients who received onabotulinumtoxinA in both treatments 1 and 2 (median duration 37 days); the majority of these were de novo CIC (17/469, 3.6%). Only 9 of the 469 (1.9%) patients who received onabotulinumtoxinA treatments twice required CIC within 12 weeks following each treatment. Correspondingly, the CIC rate was 3.1% for patients who received their first onabotulinumtoxinA treatment at treatment 2 (18/582). Following the first treatment, the mean/percentage change in UI episodes/day with onabotulinumtoxinA and placebo from baseline (5.4 and 5.4 episodes/day) to week 12 was -2.9/-54.0% and -1.1/-16.3%, respectively. Similar reductions in UI episodes/day were observed 12 weeks following the second treatment in patients receiving onabotulinumtoxinA for the first time (-3.6/-61.8%) and in those receiving a second onabotulinumtoxinA treatment (-3.5/-57.9%). A higher proportion of onabotulinumtoxinA- vs placebo-treated patients were completely continent at week 12 post-treatment (29.0% vs 8.5%, respectively), and this was consistent 12 weeks following retreatment in patients receiving a first and second treatment of onabotulinumtoxinA (32.6% and 27.1%). A higher proportion of onabotulinumtoxinA- vs placebo-treated patients achieved a ≥50% reduction in UI episodes/day (64.4% vs 32.3%, respectively) that was similar following a second treatment in patients receiving onabotulinumtoxinA for the first and second time (71.0% and 63.5%). Mean changes from baseline to week 12 in KHQ RL and SL domains were -21.9 and -21.6, respectively, with onabotulinumtoxinA (both exceeding the minimally important difference of 5 points) and -4.0 and -6.0 with placebo. Following treatment 2, mean changes from baseline to week 12 in KHQ RL and SL domains were -23.8 and -20.3 in patients receiving a first and -23.3 and -22.7 in patients receiving a second treatment of onabotulinumtoxinA. The proportions of patients with improvement/great improvement in urinary symptoms on the TBS 12 weeks following treatment 1 were 55.2% and 26.5% in patients treated with onabotulinumtoxinA and placebo, respectively, and 62.4% and 59.3% following retreatment in patients receiving onabotulinumtoxinA for a first and second time. No unexpected safety signals were observed, and urinary tract infection was the most commonly reported adverse event in the first 12 weeks of both treatment cycles.

In this large, pooled population of OAB patients, the incidence of CIC was low with onabotulinumtoxinA 100U, and no increased risk of CIC was seen with retreatment. Less than 2% of patients who received a second onabotulinumtoxinA treatment required CIC within 12 weeks of both treatments 1 and 2. Improvements in urinary symptoms and QOL were consistent following initial treatment and retreatment with onabotulinumtoxinA 100U and were similar to those reported in prior phase 3 randomized controlled clinical trials.

No increased risk of CIC was observed with onabotulinumtoxinA retreatment, and a limited number of patients (9/469, 1.9%) needed CIC after both initial treatment and retreatment. OnabotulinumtoxinA 100U improved urinary symptoms and QOL and was well tolerated with initial treatment and retreatment.

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