Cindy L Amundsen1, Yuko M Komesu2, Christopher Chermansky3, W Thomas Gregory4, Deborah L Myers5, Emily F Honeycutt6, Sandip P Vasavada7, John N Nguyen8, Tracey S Wilson9, Heidi S Harvie10, Dennis Wallace6. 1. Department of Obstetrics and Gynecology, Duke University, Durham, North Carolina, USA. Electronic address: cindy.amundsen@duke.edu. 2. Department of Obstetrics and Gynecology, University of New Mexico, Albuquerque, New Mexico, USA. 3. Department of Urology, University of Pittsburgh, Pennsylvania, USA. 4. Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, Oregon, USA. 5. Department of Obstetrics and Gynecology, Brown University, Providence, Rhode Island, USA. 6. Social, Statistical, and Environmental Sciences, RTI International, Research Triangle Park, North Carolina, USA. 7. Department of Urology, Cleveland Clinic, Cleveland, Ohio, USA. 8. Department of Obstetrics and Gynecology, Kaiser Permanente San Diego, California, USA. 9. Department of Urology, University of Alabama at Birmingham, Birmingham, Alabama, USA. 10. Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Abstract
BACKGROUND:Urgency urinary incontinence (UUI) is a chronic condition for which sacral neuromodulation (SNM) (InterStim/Medtronic) and onabotulinumtoxinA (BTX) (BotoxA/Allergan) are utilized. These therapies have not been compared over extended time. OBJECTIVE: To compare UUI episodes (UUIE) over 24 mo following SNM or BTX. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, open-label, randomized, extension trial (February 2012-July 2016) at nine US medical centers involving 386 women with ≥6 UUIE over 3 d inadequately managed by medications. Participants were clinical responders to treatment: ≥50% reduction in UUIEs after SNM placement or 1 mo post BTX. INTERVENTION: SNM (n=194) versus 200 U BTX (n=192). SNM reprogrammings occurred throughout the 24 mo. After 6 mo, two additional BTX injections were allowed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome: change in mean daily UUIE over 24 mo. SECONDARY OUTCOMES: no UUIE, ≥75% and ≥50% UUIE reduction; Overactive Bladder Questionnaire Short Form; Urinary Distress Inventory short form; Incontinence Impact Questionnaire; Patient Global Impression of Improvement; Overactive Bladder Satisfaction of Treatment Questionnaire; and adverse events (AEs). Primary analysis used a linear mixed model. RESULTS AND LIMITATIONS: Outcome data were available for 260/298 (87%) clinical responders. No difference in decreased mean UUIE was found over 24 mo (-3.88 vs -3.50 episodes/d,95% confidence interval [CI]=-0.14-0.89; p=0.15), with no differences in UUI resolution, ≥75% or ≥50% UUIE reduction. BTX group maintained higher satisfaction (mean difference=-9.14, 95% CI=-14.38--3.90; p<0.001), treatment endorsement (mean difference=-12.16, 95% CI=-17.7--6.63; p<0.001) through 24 mo. Other secondary measures did not differ. Recurrent urinary tract infections (UTIs) were higher after BTX (24% vs 10%; p<0.01), 6% required intermittent catheterization post second injection. SNM revision and removals occurred in 3% and 9% patients, respectively. CONCLUSIONS: Both treatments offered sustainable UUI improvement, and higher BTX dosing had low clean intermittent catheterization rates, but with UTI risk. SNM revision/removal rates were low due to standardized lead placement with strict treatment response definitions. PATIENT SUMMARY: We compared a large group of US women with severe urgency urinary incontinence (UUI) who receivedsacral neuromodulation (InterStim) or onabotulinumtoxinA (Botox A) therapy during a 2-yr period. We found that both therapies had similar success in reducing UUI symptoms, and adverse events were low. However, women in the BotoxA group had higher satisfaction and endorsement with their treatment, but with a higher chance of a urinary tract infection. We conclude that both therapies offer sustained reduction in daily incontinence over 2 yr.
RCT Entities:
BACKGROUND:Urgency urinary incontinence (UUI) is a chronic condition for which sacral neuromodulation (SNM) (InterStim/Medtronic) and onabotulinumtoxinA (BTX) (BotoxA/Allergan) are utilized. These therapies have not been compared over extended time. OBJECTIVE: To compare UUI episodes (UUIE) over 24 mo following SNM or BTX. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, open-label, randomized, extension trial (February 2012-July 2016) at nine US medical centers involving 386 women with ≥6 UUIE over 3 d inadequately managed by medications. Participants were clinical responders to treatment: ≥50% reduction in UUIEs after SNM placement or 1 mo post BTX. INTERVENTION: SNM (n=194) versus 200 U BTX (n=192). SNM reprogrammings occurred throughout the 24 mo. After 6 mo, two additional BTX injections were allowed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome: change in mean daily UUIE over 24 mo. SECONDARY OUTCOMES: no UUIE, ≥75% and ≥50% UUIE reduction; Overactive Bladder Questionnaire Short Form; Urinary Distress Inventory short form; Incontinence Impact Questionnaire; Patient Global Impression of Improvement; Overactive Bladder Satisfaction of Treatment Questionnaire; and adverse events (AEs). Primary analysis used a linear mixed model. RESULTS AND LIMITATIONS: Outcome data were available for 260/298 (87%) clinical responders. No difference in decreased mean UUIE was found over 24 mo (-3.88 vs -3.50 episodes/d,95% confidence interval [CI]=-0.14-0.89; p=0.15), with no differences in UUI resolution, ≥75% or ≥50% UUIE reduction. BTX group maintained higher satisfaction (mean difference=-9.14, 95% CI=-14.38--3.90; p<0.001), treatment endorsement (mean difference=-12.16, 95% CI=-17.7--6.63; p<0.001) through 24 mo. Other secondary measures did not differ. Recurrent urinary tract infections (UTIs) were higher after BTX (24% vs 10%; p<0.01), 6% required intermittent catheterization post second injection. SNM revision and removals occurred in 3% and 9% patients, respectively. CONCLUSIONS: Both treatments offered sustainable UUI improvement, and higher BTX dosing had low clean intermittent catheterization rates, but with UTI risk. SNM revision/removal rates were low due to standardized lead placement with strict treatment response definitions. PATIENT SUMMARY: We compared a large group of US women with severe urgency urinary incontinence (UUI) who received sacral neuromodulation (InterStim) or onabotulinumtoxinA (Botox A) therapy during a 2-yr period. We found that both therapies had similar success in reducing UUI symptoms, and adverse events were low. However, women in the BotoxA group had higher satisfaction and endorsement with their treatment, but with a higher chance of a urinary tract infection. We conclude that both therapies offer sustained reduction in daily incontinence over 2 yr.
Authors: Diane Borello-France; Kathryn L Burgio; Patricia S Goode; Alayne D Markland; Kimberly Kenton; Aarthi Balasubramanyam; Anne M Stoddard Journal: Phys Ther Date: 2010-07-29
Authors: Cindy L Amundsen; Holly E Richter; Shawn A Menefee; Yuko M Komesu; Lily A Arya; W Thomas Gregory; Deborah L Myers; Halina M Zyczynski; Sandip Vasavada; Tracy L Nolen; Dennis Wallace; Susan F Meikle Journal: JAMA Date: 2016-10-04 Impact factor: 56.272
Authors: Cindy L Amundsen; Holly E Richter; Shawn Menefee; Sandip Vasavada; David D Rahn; Kim Kenton; Heidi S Harvie; Dennis Wallace; Susie Meikle Journal: Contemp Clin Trials Date: 2014-01-30 Impact factor: 2.226
Authors: Roger Dmochowski; Christopher Chapple; Victor W Nitti; Michael Chancellor; Karel Everaert; Catherine Thompson; Grace Daniell; Jihao Zhou; Cornelia Haag-Molkenteller Journal: J Urol Date: 2010-10-16 Impact factor: 7.450
Authors: Anne P Cameron; Jennifer T Anger; Rodger Madison; Christopher S Saigal; J Quentin Clemens Journal: Neurourol Urodyn Date: 2012-07-27 Impact factor: 2.696
Authors: Steven Siegel; Karen Noblett; Jeffrey Mangel; Tomas L Griebling; Suzette E Sutherland; Erin T Bird; Craig Comiter; Daniel Culkin; Jason Bennett; Samuel Zylstra; Fangyu Kan; Elizabeth Thiery Journal: Urology Date: 2016-04-27 Impact factor: 2.649
Authors: Rajan Veeratterapillay; Chris Harding; Luke Teo; Nikhil Vasdev; Ahmed Abroaf; Trevor J Dorkin; Robert S Pickard; Tahseen Hasan; Andrew C Thorpe Journal: Int J Urol Date: 2013-07-02 Impact factor: 3.369
Authors: Benjamin Abelson; Steve Majerus; Daniel Sun; Bradley C Gill; Eboo Versi; Margot S Damaser Journal: Nat Rev Urol Date: 2019-05 Impact factor: 14.432
Authors: Caroline G Elmer-Lyon; Judy A Streit; Elizabeth B Takacs; Patrick P Ten Eyck; Catherine S Bradley Journal: Int Urogynecol J Date: 2019-06-20 Impact factor: 2.894
Authors: Uduak U Andy; Cindy L Amundsen; Emily Honeycutt; Alayne D Markland; Gena Dunivan; Keisha Y Dyer; Nicole B Korbly; Megan Bradley; Sandip Vasavada; Donna Mazloomdoost; Sonia Thomas Journal: Am J Obstet Gynecol Date: 2019-06-15 Impact factor: 8.661