Hypothesis / aims of study
OnabotulinumtoxinA 100U has been demonstrated to reduce urinary incontinence and significantly improve quality of life in patients with idiopathic overactive bladder (OAB) in 2 large, randomized, placebo-controlled, phase 3 trials.(1,2) However, data reporting onabotulinumtoxinA use in everyday clinical practice are limited and little information is available regarding the concomitant use of other OAB medications. Here we present the results from a large, first of its kind, prospective, observational, multinational study in OAB patients performed in a real-world setting.
Study design, materials and methods
This was an observational, non-randomized multicenter study (NCT02161159) performed in 4 European countries (Germany, Spain, Sweden, and the United Kingdom). Patients aged ≥18 years with symptoms of OAB inadequately managed with ≥1 anticholinergic received onabotulinumtoxinA per their physician’s normal clinical practice. All patients were naive to botulinum toxin type-A for the treatment of OAB. Efficacy and safety analyses were conducted on the safety population (patients who received ≥1 dose of onabotulinumtoxinA). Outcomes reported here include: mean change from baseline in number of UI episodes/day at weeks 1 and 12 post-treatment, proportion of patients with 100% and ≥50% reduction in urinary incontinence episodes/day from baseline, proportion of patients with a positive response (urinary symptoms improved/greatly improved) on the treatment benefit scale (TBS) at week 12, use of incontinence products at baseline and week 12, and use of anticholinergics or other medications for OAB (baseline, week 1, and week 12). Adverse events (AEs) and adverse drug reactions (ADRs) were also recorded up to 12 months post-treatment.
Women comprised 85% of the total study population. On average, patients were in their mid-60s with a mean of approximately 7 years since initial onset of symptoms, and most were living independently at home (94%). Significant reductions in urinary incontinence episodes/day were observed as early as week 1 (–2.4) that were sustained until week 12 (–3.0). Over 25% of patients became completely continent (i.e. 100% reduction in UI episodes/day) within 1 week after treatment. This increased to 41.8% at week 12. In addition, a ≥50% reduction in UI episodes/day was seen in more than 60% of patients at week 1, increasing to 73.9% at week 12. A positive treatment response at week 12, as assessed by the patients on the TBS, was seen in 87.6% (304/347) of patients with available TBS data. At baseline the mean number of incontinence products (total of pads/liners and diaper pants) used over the prior month was 74.3 this number significantly decreased (p<0.001) to a mean of 32.1 incontinence products in the month prior to week 12. More specifically pad/liner usage more than halved from a mean of 67.7 in the month prior to baseline to only 29.9 pads/liners in the month prior to week 12. Whilst diaper pant usage decreased even more dramatically to only a third of baseline usage (mean of 13.9 during month prior to baseline versus 4.4 during month prior to week 12).
At baseline, the prior or concomitant use of ≥1 OAB medication was documented in 469/504 patients (93.1%). Most patients (85.3%) used anticholinergics with solifenacin being the most frequently used (39.7%), followed by trospium (33.1%) and fesoterodine (24.8%); oxybutynin transdermal patches were used by 65 patients (12.9%) and darifenacin by 53 patients (10.5%). The use of the beta-3 adrenergic agonist mirabegron was documented in 183 patients (36.3%) at baseline.
At baseline, 52 out of 504 patients (10.3%) documented that they intended to continue OAB medications following onabotulinumtoxinA treatment. However, during week 1 this number decreased by approximately half to only 29 patients (5.8%) and at week 12 only 12 patients (2.4%) were still using OAB medications. Treatment with solifenacin continued in 7 patients (1.4%) at Week 1 and in 2 patients (0.4%) at Week 12. Other anticholinergics were less frequently used. Treatment with the beta-3 adrenergic agonist mirabegron was ongoing in 13 patients (2.6%) at Week 1 and in 7 patients (1.4%) at Week 12.
Throughout the first treatment cycle a total of 57 AEs were reported in 38/504 patients (7.5%); 9 patients experienced serious AEs. Overall, 17 ADRs (all non-serious) were reported by 13/504 (2.6%) patients; 7 patients reported mild ADRs, 5 moderate, and 1 severe. Urinary retention was the most frequent ADR, reported in 5 patients (1.0%), one of which was severe. Urinary tract infection was reported in two patients (0.4%).
Interpretation of results
In this real-world study, significant improvements in urinary incontinence and quality of life as well as a reduced reliance upon incontinence products were seen in OAB patients as early as week 1 after onabotulinumtoxinA treatment and were sustained to at least week 12. In addition there was a reduced use of other medications for OAB, within the first week with further reductions by week 12, even in patients who had intended to continue the OAB medications. No new safety signals related to onabotulinumtoxinA treatment were identified and the incidence of urinary retention and urinary tract infections in this real-world study was much lower than that reported in the phase 3 studies that contained criteria that were developed for the purpose of those clinical trials.