Hypothesis / aims of study
In clinical trials of onabotulinumtoxinA treatment of overactive bladder (OAB) with urinary incontinence (UI), the majority of patients were females, with limited data provided on males. In order to evaluate the efficacy and safety of onabotulinumtoxinA in a sufficient number of male patients with OAB and UI, data from four randomized clinical trials were pooled to provide this novel analysis.
Study design, materials and methods
Data were pooled from four randomized, double-blind, placebo-controlled trials conducted in North America and Europe (the two pivotal trials [ClinicalTrials.gov identifiers: NCT00910845 and NCT00910520] and two post-marketing studies [NCT01767519 and NCT01945489]). All studies had the same study design and similar inclusion criteria, including adult patients with OAB and UI that was inadequately managed by ≥1 anticholinergic. Patients were randomized to treatment with onabotulinumtoxinA 100U or placebo. Outcome measures from all four pooled studies included the number of urinary incontinence (UI) episodes/day and the Incontinence Quality of Life (I-QOL) total summary score. All studies except NCT01945489 included the Treatment Benefit Scale (TBS), which measures the patients' perception of change in their condition; 'greatly improved' and 'improved' are considered positive treatment responses. Each efficacy measure is reported as the change from baseline at week 12 following the first treatment. Since the four trials were conducted at different times and sites, only descriptive data are reported. Treatment-emergent adverse events (TEAEs) are reported for the first 12 weeks following treatment.
The overall pooled intent-to-treat population (N=1564) was composed of 194 males (12.4%) and 1370 females (87.6%). Baseline demographic and disease characteristics were similar between the sexes as well as across treatment groups, with a mean age of 61.8 ± 14.6 in males and 60.4 ± 13.3 in females. The mean UI episodes/day at baseline were 4.9 in males and 5.5 in females. At week 12 following treatment, UI episodes/day improved with onabotulinumtoxinA, with mean changes from baseline of -2.2 and -1.3 in males treated with onabotulinumtoxinA and placebo, respectively; decreases in females were -3.0 and -1.1, respectively. The mean change from baseline in the mean I-QOL total summary score was 14.4 and 7.3 in the onabotulinumtoxinA-treated and placebo-treated males, respectively, and 24.3 females and 7.1 in onabotulinumtoxinA-treated and placebo-treated females, respectively. Notably, both males and females treated with onabotulinumtoxinA achieved mean I-QOL increases above the minimal important difference of 10 points whereas the placebo-treated patients did not. The proportion of patients with a positive response on the TBS at week 12 was 44.3% in males treated with onabotulinumtoxinA, 27.5% in males who received placebo, 66.1% in females treated with onabotulinumtoxinA, and 29.7% in females who received placebo. The overall incidence of TEAEs in the 12 weeks following treatment was higher in females than males (39.4% and 34.7%, respectively). The most common TEAEs in males were dysuria (6.3% and 9.6% with onabotulinumtoxinA and placebo, respectively), increased residual urine volume (8.3% and 5.3%), and hematuria (5.2% and 8.2%); while in females, urinary tract infection (13.4% and 12.6%), dysuria (6.0% and 3.5%), and bacteriuria (3.3% and 3.9%) were most common. Urinary retention was lower in females (3.6% and 1.7%) than in males (5.2% and 4.3%).
Interpretation of results
Clinically meaningful treatment benefits in all efficacy measures including quality of life were observed with onabotulinumtoxinA 100U regardless of sex. The overall TEAE profile with onabotulinumtoxinA treatment was generally limited to local urological events. No new safety issues in males were identified, and the types and incidences of TEAEs were consistent with previous findings.