The aim of this study was to assess whether intradetrusor injection of 100 units of onabotulinimtoxinA (BTX) is superior to midurethral sling (MUS) for women with mixed urinary incontinence (MUI) symptoms refractory to conservative treatment and oral medications.
Study design, materials and methods
A randomized, multi-center trial of BTX vs. MUS for the treatment of MUI was conducted. Eligible participants reported at least moderate bother from both stress (SUI) and urgency (UUI) incontinence symptoms based on the Urogenital Distress Inventory (UDI), demonstrated objective SUI, and had >4 UUI episodes on 3-day bladder diary. Randomization was 1:1, stratified by site and age (≥65, <65). BTX recipients could receive an additional injection between 3-6 months. Participants could receive additional treatment (including crossover to the alternative intervention) between 6-12 months. Additional treatment prior to 6 months was a protocol violation. The primary outcome was change from baseline in UDI total score at 6 months. Other efficacy outcomes included UDI sub-scores, bladder diary, and other symptom, quality of life and global impression outcomes. Groups were compared via repeated measures linear models, adjusting for site, age category, and baseline UDI severity.
Results
137 participants were randomized, treated, and had post-baseline data (71 BTX, 66 MUS). Figure 1 shows the Consort diagram of the MUSA RCT. Mean age was 59 (±11.5) years, 80% were White, 15% were Black/African American, and 15% were Latina. Mean BMI was 34.6 (±7.9).
Both groups reported improvement in total-UDI score at 6 months with no difference between the BTX and MUS groups (-67 vs. -85 points, BTX-MUS mean difference 18, 95% CI -5 to 41, P=0.12). The UDI-irritative and UDI-stress scores also improved in both groups at 6 months. While there was no difference in UDI-irritative score between groups (-33 vs. -27 points, BTX-MUS mean difference -6, 95% CI -15 to 4, P=0.27), the MUS group had greater UDI-stress score improvement (-45 points) than BTX (-25, BTX-MUS mean difference 20, 95% CI 8 to 32, P< 0.001). At 12 months, the MUS group had greater improvement than BTX in both the total-UDI and UDI-stress scores but not the UDI-irritative score (Figure 2).
In the BTX group, 13% received a second injection by 6 months and 28% by 12 months. There was no difference in receipt of crossover treatment between BTX and MUS groups at 6 months (3% vs 8%, P=0.26), but by 12 months there was a higher number in the MUS group that received BTX compared to those in the BTX group that received MUS (30% versus 15% respectively, P=0.04).
Both groups reported improvement at 6 and 12 months with no difference between groups in the Overactive Bladder Questionnaire (OAB-q), Overactive Bladder Health-related Quality of Life (OAB-HRQOL) and Overactive Bladder Satisfaction Questionnaire (OAB-SAT-q) (Figure 3). There was no difference in reduction in UUI episodes per day (6 months: -1.9 vs. -1.4, BTX-MUS mean difference -0.5, 95% CI -1.4 to 0.4, P=0.31; 12 months: -1.7 vs. -1.7, BTX-MUS mean difference 0.1, 95% CI -1.0 to 1.1 P=0.88). However, at 6 months, patients that received a MUS had an improvement over BTX in reduction of SUI episodes per day (-1.9 vs. -1.0, BTX-MUS mean difference 0.9, 95% CI 0.5 to 1.4, p<0.001) and reduction of total UI episodes per day (-4.0 vs. -2.9, BTX-MUS mean difference 1.1, 95% CI 0.0 to 2.2, p=0.05).
Interpretation of results
In this randomized trial of women with moderate or greatly bothersome MUI, the total-UDI, UDI-irritative and UDI-stress scores improved in both groups at 6 months, and improvement was seen through 12 months. As expected, patients receiving a MUS had greater UDI-stress score improvement compared to those that received BTX, and this improvement was noted at all follow up time points after treatment. The results from this RCT support allowing individualized treatment approaches based on patients’ preferences.
Concluding message
Both BTX and MUS treatment approaches are associated with improvement in MUI symptoms at 6 and 12 months, thereby allowing for individualized treatment approaches based on patients’ preferences.
Figure 1
Figure 2
UDI total score (A, range 0 – 300), irritative subscale (B, range 0 – 100), and stress subscale (C, range 0 – 100) change from baseline means and 95% CI. MCID is 26.1 for total score, 10.2 for irritative subscale, and 5.4 for stress subscale.
Figure 3
OAB-q (A), OAB-HRQOL (B), OAB-SAT-q (C) change from baseline means and 95% CI. The range is 0 – 100 for each score, with higher scores indicating greater symptom severity (A), better QOL (B), or greater treatment satisfaction (C).
