Data on long-term, repeat treatment with onabotulinumtoxinA for overactive bladder (OAB) and urinary incontinence (UI) have typically had small numbers of male participants, making interpretation of results in this subpopulation difficult. In this novel, gender-focused analysis, the long-term safety effects of onabotulinumtoxinA for the treatment of OAB and UI were evaluated by pooling data from four randomized clinical trials, each of which allowed up to two treatments, and a long-term extension study.

Safety data were pooled from patients who received up to two treatments in one of the following randomized, double-blind, placebo-controlled trials: ClinicalTrials.gov identifiers NCT00910845, NCT00910520, NCT01767519, and NCT01945489. In addition, data were integrated with the long-term extension study (NCT00915525) that enrolled patients from the pivotal trials with up to three years of follow up. All studies included adult patients with OAB with UI that was inadequately managed by ≥1 anticholinergic. Patients in the double-blind portions of the trials were randomized to treatment with onabotulinumtoxinA 100U or placebo. A subsequent, open-label treatment could be received by those in either dose group beginning at week 12 from the prior treatment if they requested it and qualified with two or more urgency UI episodes as recorded in a three-day bladder diary and a post-void residual urine volume less than 200 mL. Data are presented here by the patients' treatment cycles with onabotulinumtoxinA; therefore, patients who received placebo in the first treatment cycle and onabotulinumtoxinA in the open-label second treatment cycle are included in the first onabotulinumtoxinA treatment cycle. Urological treatment-emergent adverse events (TEAEs) of interest are reported for the first 12 weeks of each treatment cycle. The first four treatment cycles are shown here since fewer than 20 male patients received five or more onabotulinumtoxinA treatments.

The overall pooled safety population for those who received at least one onabotulinumtoxinA treatment included 133 males (11.0%) and 1071 females (89.0%). Urological TEAEs of interest were consistent over the four onabotulinumtoxinA treatment cycles, and did not increase in frequency after repeated treatments (Table 1). Hematuria and urinary retention occurred at higher rates in males, and urinary tract infection (UTI) occurred at higher rates in females. All male patients were able to spontaneously void.

Repeat treatment with onabotulinumtoxinA had an acceptable safety profile in males as well as in females. Urological TEAEs of interest were consistent over the four treatment cycles, particularly in females, which comprised the much larger subpopulation. In the smaller male population, urological TEAEs were consistent and did not increase over repeat treatment cycles. The observed higher incidence of hematuria in males and UTI in females likely reflects anatomical differences between sexes. Hematuria may be associated with the procedure of inserting a cystoscope through a longer urethra in males, and increased UTI in females may be due to the known risk factors such as a shorter urethra, some types of birth control, and menopause. The incidence of urinary retention (elevated residual necessitating intermittent catheterization) was low, ranging across cycles from 1.6-2.3% in females and 1.7-6.1% in males. Differences may be due to the male anatomy and presence of BPH in some males.

The results of this pooled analysis, which includes the largest reported long-term male subpopulation, show that onabotulinumtoxinA was well tolerated in both males and females. No new safety signals were observed in males with long-term treatment with onabotulinumtoxinA.