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Clinical Trial
. 2025 Jun 3;333(21):1887-1896.
doi: 10.1001/jama.2025.4682.

Midurethral Sling vs OnabotulinumtoxinA in Females With Urinary Incontinence: The MUSA Randomized Clinical Trial

Heidi S Harvie  1   2 , Shawn A Menefee  3 , Holly E Richter  4 , Vivian W Sung  5 , Christopher J Chermansky  6 , David D Rahn  7 , Cindy L Amundsen  8 , Lily A Arya  1 , Evan Rhodes  9 , Donna Mazloomdoost  10 , Sonia Thomas  9 ; National Institute of Child Health and Human Development Pelvic Floor Disorders Network
Collaborators, Affiliations
Clinical Trial

Midurethral Sling vs OnabotulinumtoxinA in Females With Urinary Incontinence: The MUSA Randomized Clinical Trial

Heidi S Harvie et al. JAMA. .

Abstract

Importance: Mixed urinary incontinence, which includes both stress and urgency urinary incontinence, adversely affects quality of life and can be difficult to manage. Studies comparing procedural-based treatments for mixed urinary incontinence are lacking.

Objective: To determine whether intradetrusor onabotulinumtoxinA is more effective than midurethral sling for the treatment of mixed urinary incontinence in females.

Design, setting, and participants: Randomized, superiority trial involving females (aged ≥21 years) with moderate to severe bother from both stress and urgency urinary incontinence who had unsuccessful conservative treatments and oral medications. The study was conducted at 7 US sites with enrollment between July 2020 and September 2022; the last date of follow-up was December 29, 2023.

Interventions: Intradetrusor injection of onabotulinumtoxinA, 100 U (treatment focused on the urgency component), vs surgical synthetic mesh midurethral sling (treatment focused on the stress component). Recipients of onabotulinumtoxinA could receive an additional injection between 3 and 6 months. All participants could receive additional treatment (including crossover to the alternative treatment) between 6 and 12 months.

Main outcomes and measures: The primary outcome was change at 6 months in mixed incontinence symptoms as measured by the Urogenital Distress Inventory (UDI) total score (0-300 points; higher scores indicate worse symptoms; minimal clinically important difference, 26.1). Secondary outcomes included stress and irritative UDI subscores.

Results: Among 150 females randomized, 137 were treated, had postbaseline outcome data, and were included in the primary analysis (mean [SD] age, 59.0 [11.5] years). Both groups demonstrated mean improvement in UDI total score at 6 months with no significant difference between groups (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). For secondary outcomes, greater UDI stress score improvement was seen with the sling (-45.2 [95% CI, -53.7 to -36.8]) compared with onabotulinumtoxinA (-25.1 [95% CI, -34.1 to -16.1]) (P < .001); however, no significant difference was seen between groups 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). In the onabotulinumtoxinA group, 12.7% and 28.2% received a second injection by 6 and 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 were not different between groups.

Conclusions and relevance: There was no observed difference in UDI total score improvement at 6 months between the onabotulinumtoxinA and midurethral sling groups in females with moderate to severe mixed urinary incontinence who previously did not respond to conservative treatments. These findings may help inform treatment decisions based on patient preference in partnership with clinician recommendations.

Trial registration: ClinicalTrials.gov Identifier: NCT04171531.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Harvie reported receiving grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and National Institutes of Health (NIH) Office of Research on Women’s Health–sponsored Pelvic Floor Disorders Network during the conduct of the study. Dr Menefee reported receiving grants from the Patient-Centered Outcomes Research Institute (PCORI) to institution outside the submitted work and royalties from UpToDate on an unrelated topic. Dr Richter reported receiving grants from PCORI, NIH/National Institute on Aging (NIA), NIH/University of Pennsylvania, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)/Mayo, NIDDK/University of Alabama, Cosm Medical, Reia, Renovia, NIA/UT Southwestern, NIH/University of Minnesota, EBT Medical, NICHD/University of Texas at Austin, and Allergan; being a data and safety monitoring board (DSMB) member for BlueWind Medical and for Veristat; receiving royalties from UpToDate; serving on the board of directors for WorldWide Fistula Fund and SOLACE and the editorial board for International Urogynecology Journal; and serving as an editor for Current Geriatrics Reports and a consultant for Neomedic, Coloplast, Palette Life Sciences, Laborie, Moremme, ICA, Axena Health, and Lily Medical during the conduct of the study. Dr Sung reported receiving grants from NICHD during the conduct of the study. Dr Rahn reported receiving grants from NICHD during the conduct of the study and grants from the American Board of Obstetrics & Gynecology and the American Association of Obstetricians and Gynecologists Foundation outside the submitted work. Dr Amundsen reported receiving grants from the NICHD during the conduct of the study and grants and personal fees from BlueWind Medical outside the submitted work. Dr Arya reported receiving grants from the NICHD during the conduct of the study and personal fees from Urovant Sciences outside the submitted work. Dr Rhodes reported receiving grants from the NICHD during the conduct of the study. Dr Mazloomdoost reported receiving grants from the NIH during the conduct of the study and being employed by the NIH. Dr Thomas reported receiving grants from the NICHD during the conduct of the study. No other disclosures were reported.

Comment in

References

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