OnabotulinumtoxinA Works Long-Term for UI

Atlanta—Patients with urinary incontinence (UI) due to neurogenic detrusor overactivity, who were inadequately managed with anticholinergics, experienced sustained reductions in UI episodes and improvements in quality of life with repeated onabotulinumtoxinA treatments.

Researchers presented the data during a poster session at the AUA meeting. The poster was titled Long-Term Efficacy and Safety of OnabotulinumtoxinA in Patients with Urinary Incontinence Due to Neurogenic Detrusor Overactivity.

The study findings were based on an interim analysis of an ongoing long-term extension study of 2 pivotal, phase 3, randomized, placebo-controlled studies designed to evaluate the efficacy and safety of onabotulinumtoxinA over repeated cycles. Patients who completed either of the phase 3 studies were eligible to enter the 3-year extension study in which they received multiple intradetrusor treatments of onabotulinumtoxinA 200U or 300U. Patients who received onabotulinumtoxinA in the phase 3 study received the same dose in the extension study, while patients who received placebo during the phase 3 study received onabotulinumtoxinA in the extension study.

The primary end point was change from study baseline in weekly UI episodes at week 6 following each treatment. Other efficacy variables at week 6 following each treatment included the proportion of patients with ≥50% and 100% reductions in UI episodes, Incontinence Quality of Life Questionniare (I-QOL) responder rates, and time to patient request for retreatment. Adverse events were also monitored.

A total of 1123 patients received up to 5 cycles of onabotulinumtoxinA as of the interim cut (cycle 1=387 patients, cycle 2=336 patients, cycle 3=241 patients, cycle 4=113 patients, and cycle 4=46 patients). The results showed that weekly UI episodes significantly and consistently decreased following repeated onabotulinumtoxinA treatment. Reductions from baseline were –22.7, –23.3, –23.1, –25.3, and –31.9 in the 200U group and –23.8, –25.0, –23.6, –24.1, and –29.5 in the 300U group in treatment cycles 1 through 5, respectively.

The majority of patients achieved ≥50% reduction from baseline in UI episodes over repeated onabotulinumtoxinA treatment cycles. For the 200U group, the percentage of patients who achieved ≥50% reduction in cycles 1 through 5 was 83.1%, 83.9%, 80.6%, 73.3%, and 94.4%, respectively. For the 300U group, the percentage of patients who achieved ≥50% reduction in cycles 1 through 5 was 84.2%, 86.0%, 82.8%, 86.4%, and 88.2%, respectively. Furthermore, a relevant percentage of patients achieved a 100% reduction from baseline (“dry”) in UI episodes.

The researchers also found that the majority of patients (66%-93%) achieved ≥11 point increase in total I-QOL scores at 6 weeks following repeated treatment with onabotulinumtoxinA 200U (71.7%, 80.4%, 72.2%, 73.9%, and 88.2%) and 300U (77.2%, 73.3%, 66.3%, 72.1%, and 93.3%) during treatment cycles 1 through 5, respectively. Time to patient request for retreatment remained fairly consistent over cycles 1 and 2, which the majority of patients had completed (approximately 250 days; 36 weeks). However, time to patient request for retreatment showed a marginal decline in later cycles. The investigators noted that it is difficult to interpret these results as the cycles are not complete and 44% to 54% of patients are receiving ongoing treatment.

The most common adverse events were urinary tract infection (UTI) and urinary retention. The incidence was similar within each treatment cycle and continued to decline through all 5 cycles for patients who received either dose of onabotulinumtoxinA 200U or 300U. For example, during cycle 5 of treatment, 5 patients in both groups experienced UTI and no patients experienced urinary retention.

“OnabotulinumtoxinA was well tolerated, and no new safety signals were observed with repeat treatment,” the investigators concluded.

This study was supported by Allergan, Inc.