Hypothesis / aims of study
Results from clinical trials (1-3) conducted to assess the outcomes of treatment with onabotulinumtoxinA at a dose of 100U in patients with idiopathic overactive bladder (OAB) and urinary incontinence (UI), showed that onabotulinumtoxinA significantly reduced UI and improved quality of life (QoL). In these studies, onabotulinumtoxinA was administered as 20 evenly spaced intradetrusor injections avoiding the trigone. The pooled incidence of clean intermittent catheterization (CIC) use in the overall patient population from these trials was 6.2%. The present study tested the hypothesis that an alternative injection pattern for onabotulinumtoxinA of 10 injections into the trigone and peri-trigonal region could be effective and have a lower incidence of CIC use compared with the standard injection paradigm.
Study design, materials and methods
This was a multicenter, randomized, double-blind trial (Clinicaltrials.gov identifier, NCT03052764) which included adults with OAB and UI that was inadequately managed with ≥1 anticholinergic. Eligibility criteria were identical to prior phase 3 and 4 studies. Patients were randomized 2:1 to receive onabotulinumtoxinA 100U or placebo, administered as 2 trigonal and 8 peri-trigonal injections (Figure 1).
A total of 120 patients (115 females; 5 males) were randomized to receive onabotulinumtoxinA (n=80) or placebo (n=40). Mean (standard deviation [SD]) age was 61.0 (11.7) years and mean (SD) duration of OAB symptoms was 9.6 (7.6) years. The efficacy analysis included 117 patients; 112 females and 5 males. Mean baseline UI values were 6.32 episodes/day in the onabotulinumtoxinA group (n=78) and 6.34 episodes/day in the placebo group (n=39). Least squares mean reduction from baseline in UI at week 12 was significantly higher in the onabotulinumtoxinA group compared with the placebo group (-2.99 versus -0.42 episodes/day; p<0.0001). The proportions of patients who achieved 100% reduction in UI episodes/day at week 12 were 13.9% in the onabotulinumtoxinA group and 2.7% in the placebo group. The proportions of patients who achieved a ≥50% reduction in UI episodes/day at week 12 were 51.4% and 18.9%, respectively. The incidence of CIC use in the first 12 weeks was 2/78 patients (2.6%) in the onabotulinumtoxinA group and 0 in the placebo group. Both cases occurred in male patients who had additional risk factors for the development of elevated post-void residual (PVR) volume at baseline; there were no cases in female patients, who comprised 96% of the study population. There was a significant (p=.0007) improvement in mean incontinence (I)-QoL total score from baseline (onabotulinumtoxinA, 34.0; placebo, 30.7) at week 12 in the onabotulinumtoxinA (21.3) versus placebo group (-4.1). The increase from baseline to week 12 in PVR volume was 39.8 mL in the onabotulinumtoxinA group (baseline: 19.2 mL) and 18.6 mL in the placebo group (baseline: 19.2 mL; p=.0165). Adverse events were predominantly mild/moderate; urinary tract infection was the most common, occurring in 35.9% of onabotulinumtoxinA-treated patients and in 25.6% of patients who received placebo. Adverse event outcomes were consistent with those for the onabotulinumtoxinA OAB indication using the traditional injection paradigm.
Interpretation of results
Although not a direct comparison, CIC use in patients who received the alternative onabotulinumtoxinA injection paradigm with fewer injection points in this study was lower than that reported in phase 3 and 4 studies that used the traditional paradigm (2.6% vs 6.2%). This could possibly be due to injections being more targeted to afferent trigonal nerves, thus decreasing efferent motor effects that could result in reduced voiding efficiency and the need to perform CIC. CIC use occurred in male patients with a medical history of benign prostatic hyperplasia and/or enlarged prostate, there were no cases of CIC in female patients.