, 2025-05-07 10:18:00
OnabotulinumtoxinA (Botox) injection and midurethral sling surgery yielded comparable symptom improvement in women with mixed stress-urgency urinary incontinence (MUI) at 6 months, a multicenter randomized study found. Surgery led to insignificantly better outcomes in the Mid-urethral Sling vs Botox A (MUSA) trial conducted by Heidi Harvie, MD, MBA, MSCE, associate professor of obstetrics and gynecology at Perelman School of Medicine, University of Pennsylvania, Philadelphia, and colleagues.
“[Stress-urinary incontinence] SUI is most common, followed by MUI and [urgency urinary incontinence] UUI,” said Harvie. “In the United States, MUI affects an estimated 30% of women by 60 years of age. Women with urinary incontinence typically report that UUI is more bothersome than SUI, and the combination of both is more bothersome than either UUI or SUI alone.” Of the two, MUI is the more challenging to treat.
Published online in JAMA, the MUSA trial recruited 150 women (age, 27-87 [mean, 59] years; about 55% White) from seven clinical centers in the Pelvic Floor Disorders Network, National Institute of Child Health and Human Development (NICHD). All had moderate to severe MUI with an average of seven leakage episodes per day and had not responded to conservative treatments, such as lifestyle changes and exercise, or oral medications.
From July 2020 to September 2022, participants were randomly assigned to receive either an intradetrusor injection of onabotulinumtoxinA 100 U (focusing on the urgency component) or midurethral sling (focusing on the stress urgency component). Of these, 137 received treatment, with last follow-up in December 2023.
OnabotulinumtoxinA recipients could receive an additional injection between 3 and 6 months, and all participants could receive additional treatment (including crossover to the alternative intervention) between 6 and 12 months.
The primary outcome was a change from baseline in Urogenital Distress Inventory (UDI) scores (range, 0-300) at 6 months. Secondary outcomes included a UDI change at 3 and 12 months, irritative and stress subscores of the UDI, urinary incontinence episodes, predictors of poor treatment response, quality of life, and global impression outcomes. In addition, adverse events, use of additional treatments, and cost-effectiveness were evaluated.
Both groups showed mean improvement in the UDI total score at 6 months with no significant difference in scores between groups.
- OnabotulinumtoxinA: −66.8 (95% CI, −84.9 to −48).
- Sling: −84.9 (95% CI, −100.5 to −69.3) for a mean difference of 18.1 points (95% CI, −4.6 to 40.7; P = .12).
- In secondary outcomes, there was a greater improvement in the UDI stress incontinence score with the sling at −45.2 (95% CI, −53.7 to −36.8) vs with onabotulinumtoxinA at −25.1 (95% CI, −34.1 to −16.1; P < .001).
- No significant difference emerged in the UDI irritative score with onabotulinumtoxinA at −32.9 (95% CI, −40.3 to −25.6) vs with the sling at −27.4 (95% CI, −34.6 to −20.3; P = .27).
- In the medication group, 12.7% and 28.2% received a second injection by 6 or 12 months, respectively. By 12 months, 30.3% in the sling group received onabotulinumtoxinA, and 15.5% in the onabotulinumtoxinA group received a sling.
- Overall adverse events did not differ between groups, but recurrent urinary tract infections were more common in the sling group at 17.6% vs in the onabotulinumtoxinA group at 6.9%.
Rates of surgical revision (1.5%), vaginal mesh exposure (2.9%), and short-term postprocedural urinary catheter use (11.8%) in the sling group were similar to those reported in other studies. In the onabotulinumtoxinA group, 2.8% required intermittent self-catheterization 2 weeks post-procedure.
“Midurethral sling surgery and onabotulinumtoxinA are both good options for improving MUI symptoms. However, these patients can be difficult to treat with one therapy,” Harvie told Medscape Medical News. She hopes the findings will potentially help inform treatment decisions and shared decision-making based on patient preference in partnership with clinician recommendations.
As for the economic side, her group is currently planning a cost-effectiveness analysis of the two approaches.
In an accompanying editorial on the study, obstetrician-gynecologist Brittany L. Roberts, MD, and colleagues at the Albany Medical Center in Albany, New York, agreed that shared decision-making should ultimately guide therapeutic strategy. “Because 45% of patients had another therapy within a year, it underlines that mixed urinary incontinence is a chronic disease and may require new treatments over time,” they wrote. “Future studies should explore this concept and examine the impact on the utilization of healthcare resources and patient satisfaction.”
Roberts’ group pointed out that the “clinical conundrum” of this mixed condition affects 1 in 4 women older than 65 years. “The personal and societal costs of incontinence are significant,” they wrote. By age 80, 20% will undergo surgery for SUI or MUI.
While physical and behavioral therapies improve both types, medications are standard treatment for urgency. “When conservative treatment fails, conventional guidance has been to treat the urgency before the stress component because anti-incontinence surgical procedures can worsen urgency incontinence and many urgency treatments are medical rather than surgical,” they wrote. Another strategy has been to treat whichever symptom is dominant.
Results from the Effects of Surgical Treatment Enhanced with Exercise for Mixed Urinary Incontinence (ESTEEM) trial revealed that both groups, surgery with or without behavioral and physical therapy, reported improved urgency symptoms, findings substantiated in prior cohort studies.
“While the original hypothesis of ESTEEM was that treating both components of mixed urinary incontinence with behavioral and physical therapy plus sling would result in better patient outcomes, ESTEEM revealed that urgency symptoms can improve with the midurethral sling alone, challenging previously held beliefs about the impact of anti-incontinence surgeries worsening the urgency component of mixed incontinence,” Roberts and associates wrote.
They further pointed out that combined findings from MUSA and ESTEEM revealed that the pathophysiology of stress and urge incontinence are likely intertwined. “For example, both patients and clinicians have difficulty discerning which type of leakage patients have, particularly when the incontinence is severe.” With better diagnostic clarity on urgency and stress incontinence phenotypes, more specific advice maybe offered to individuals on what to treat first.
While the MUSA trial positioned both interventions in equipoise, they have significant differences. OnabotulinumtoxinA can be administered in the clinic or operating room and requires no incision but insertion of a cystoscope. Sling surgery is performed in the operating room and typically requires three small incisions. Slings are meant to be a permanent intervention, while onabotulinumtoxinA injection must be repeated as its effects wear off.
So why not perform a sling surgery and give onabotulinumtoxinA at the same time? A randomized trial of 78 patients posing this question found that compared with sling alone, combined therapy did not show greater symptom improvement at 3 months. Additionally, the combined therapy group engaged in more self-catheterization and had more urinary tract infections.
This study was sponsored by the Eunice Kennedy Shriver NICHD and the National Institutes of Health (NIH)’s Office of Research on Women’s Health. Harvie reported receiving grants from the NICHD and NIH. Several coauthors reported receiving similar grants from government and other research-funding bodies such as the Patient-Centered Outcomes Research Institute; being employed by the NIH; or receiving research grants, royalties, and consulting or advisory fees from private sector companies.
