Phase III MUSA Trial Finds Similar Six-Month Outcomes Between Botox, Midurethral Sling in Patients with Mixed Urinary Incontinence

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Results from the Phase III MUSA trial show that in women with moderate to severe mixed urinary incontinence (MUI) who were unresponsive to conservative therapies, treatment with onabotulinumtoxinA (Botox) was not found superior to midurethral sling at six months. These findings, published by JAMA Network Open, demonstrated that both therapeutic approaches improved symptoms, but many patients needed additional treatment to sustain those benefits.^1,2

“Fundamentally, the key question is not only what procedural treatment improves MUI symptoms the most, but also what is the best treatment to receive first because many patients eventually pursue both treatments,” the study authors wrote. “The current trial hypothesized that treatment focused on the (urgency urinary incontinence [UUI]) component (onabotulinumtoxinA) would be superior to treatment focused on the (stress urinary incontinence [SUI]) component (midurethral sling).”¹

MUI is a common condition that affects approximately 30% of women aged 60 years and above. It can have a significant impact on quality of life, as involuntary leakage can occur with any exertion, such as sneezing or coughing.

Conservative treatment approaches for MUI may include behavioral therapy, pelvic floor muscle therapy, and medication. However, the study authors noted that the benefits and order of approach for advanced bladder treatment approaches, such as surgical interventions, are undetermined.

They pointed to the 2019 ESTEEM clinical trial, in which 416 patients with MUI seeking surgical intervention for SUI received compared a combination of midurethral sling plus behavioral and pelvic floor muscle therapy vs. midurethral sling alone. Investigators found that patients receiving the midurethral sling alone achieved improved SUI and UUI symptoms, but these patients were also more likely to need additional treatment sooner.

“The historical approach of treating the UUI component first with either onabotulinumtoxinA or sacral neuromodulation does not ensure improvement in the SUI component,” the authors of the current study wrote. “Similarly, until recently, there have been limited data on whether treating the SUI component with a midurethral sling would substantially improve the UUI component.”¹

Trial Design

The multicenter, randomized, superiority trial enrolled women 21 years of age and older experiencing moderate to severe bother from both stress and urgency urinary incontinence who did not respond to conservative treatments and oral medications.

A total of 150 women were randomly assigned to receive either intradetrusor injection of onabotulinumtoxinA 100 U or surgical synthetic mesh midurethral sling. Those randomly assigned to receive onabotulinumtoxinA were able to receive an additional injection between three and six months. All trial participants were eligible to receive additional therapy between six and 12 months, which included crossing over to receive the alternative treatment.

The trial’s primary endpoint was change at six months in mixed incontinence symptoms measured by Urogenital Distress Inventory (UDI) total score, which is measured on a scale of 0-300 with higher scores indicating worse symptoms. Secondary endpoints included stress and irritative UDI subscores.

Among 137 women included in the primary analysis, both cohorts demonstrated mean improvements in UDI total score at six months, with results similar between the cohorts (onabotulinumtoxinA: −66.8 points [95% CI, −84.9 to −48.8]; sling: −84.9 [95% CI, −100.5 to −69.3]; mean difference, 18.1 points [95% CI, −4.6 to 40.7]; P = .12). Investigators observed a higher UDI stress score improvement in the sling cohort (−45.2 [95% CI, −53.7 to −36.8]) compared to the onabotulinumtoxinA cohort (−25.1 [95% CI, −34.1 to −16.1]) (P < .001). There was not significant differences observed in UDI irritative score (onabotulinumtoxinA: −32.9 [95% CI, −40.3 to −25.6] vs sling: –27.4 [95% CI, −34.6 to −20.3]; P = .27).

Among patients in the onabotulinumtoxinA cohort, 12.7% were administered a second injection by six months and 28.2% were administered a second injection at 12 months. At 12 months, 30.3% of patients in the sling cohort were administered onabotulinumtoxinA and 15.5% of patients in the onabotulinumtoxinA cohort received a sling. In terms of safety, rates of adverse events were similar between the cohorts.

“Among females with moderate to severe MUI who previously did not respond to conservative treatments and oral medications, onabotulinumtoxinA injection and midurethral sling surgery resulted in no observed difference in MUI symptom improvement at 6 months,” the study authors concluded. “Moderate to severe bothersome stress and urgency incontinence can be difficult to treat with one therapy, as 22.6% received both a sling and onabotulinumtoxinA by 12 months. These findings may help inform treatment decisions based on patient preference in partnership with clinician recommendations.”¹

References

1. Harvie HS, Menefee SA, Richter HE, et al. Midurethral Sling vs OnabotulinumtoxinA in Females With Urinary Incontinence: The MUSA Randomized Clinical Trial. JAMA. Published online May 05, 2025. doi:10.1001/jama.2025.4682.

2. Sling vs Botox for Mixed Incontinence (MUSA). ClinicalTrials.gov. Updated March 20, 2025. Accessed May 6, 2025. https://clinicaltrials.gov/study/NCT04171531