Research Round-Up: Mixed Urinary Incontinence

In this issue, we have provided a small snapshot on the latest clinical research in Mixed Urinary Incontinence (MUI):

• Post-hoc analyses of pooled data from a Japanese phase IIb and a phase III study (randomized, placebo-controlled double-blind studies) showed that Mirabegron 50 mg significantly improved key overactive bladder symptoms in women with urgency urinary incontinence (Takahashi et al 2022). It also improved most overactive bladder symptoms, including micturition frequency, in patients with mixed urinary incontinence. Women with urgency urinary incontinence (placebo n = 204, mirabegron n = 214) and mixed urinary incontinence (placebo n = 122, mirabegron n = 139) were included in the studies. Change in the primary outcome, namely, mean micturition/24 h at end-of-treatment for mirabegron was statistically significant versus placebo in both populations and the effect size increased over time. Mirabegron showed larger improvements versus placebo in all quality-of-life domains, except for general health perception in the urgency urinary incontinence population. Incontinence normalization rates for mirabegron were 47.2% and 49.6% in the urgency urinary incontinence and mixed urinary incontinence populations, respectively, versus 42.6% and 39.3% for placebo. For all secondary endpoints, median changes for mirabegron were statistically significant versus placebo at end of treatment, except for nocturia for the urgency urinary incontinence population and urgency for the mixed urinary incontinence population.
• In a randomized controlled trial (Komar et al 2021) of 78 women with mixed urinary incontinence scheduled to undergo mid-urethral sling surgery, participants were randomly assigned to receive 100 units of intradetrusor onabotulinumtoxin A (41 women) or placebo (37 women) during the surgery. The primary outcome was PGI-I score at 3 months for overall incontinence. Concurrent botulinum toxin injection did not improve overall incontinence symptoms at 3 months compared with placebo. Women with mixed urinary incontinence undergoing sling surgery reported significant improvement in overall incontinence symptoms, regardless of the addition of onabotulinumtoxin A injections, but those receiving concurrent onabotulinumtoxin A injections reported less urgency severity and greater improvement in urgency symptoms at 3 months.
• In the ESTEEM randomized controlled clinical trial (Sung et al 2019), behavioral and pelvic floor muscle therapy combined with mid-urethral sling surgery resulted in a small statistically significant difference in urinary incontinence symptoms at 12 months that did not meet the prespecified threshold for clinical importance. Among 480 women who were randomized, 416 were eligible and divided into behavioral and pelvic floor muscle therapy (which included one preoperative and five postoperative sessions through 6 months) combined with mid-urethral sling (n=209) vs sling alone (n=207). Outcome was change between baseline and 12 months in mixed UI symptoms measured by Urogenital Distress inventory (UDI) long form, range 0-300 points; with higher score indicating worse symptoms. The UDI score in the combined group significantly decreased from 178.0 points at baseline to 30.7 points at 12 months, adjusted mean change −128.1 points (95% CI, −146.5 to −109.8). The UDI score in the sling-only group significantly decreased from 176.8 to 34.5 points, adjusted mean change −114.7 points (95% CI, −133.3 to −96.2). The model-estimated between-group difference (−13.4 points; 95% CI, −25.9 to −1.0; P = .04) did not meet the minimal clinically important difference threshold.
• Electroacupuncture (EA) could be a potential treatment option for MUI and is relatively safe according to a meta-analysis by Cui et al (2022). Eight randomized controlled trials comprising 847 patients were included in the analysis. Compared with antimuscarinic drugs plus pelvic floor muscle training, EA resulted in significantly less pad weight on the 1-h pad test and statistically significantly lower severity scores on the International Consultation on Incontinence Questionnaire Short Form. Trial sequential analysis used to assess the stability of the results proved that the test was stable, and the evidence was conclusive.
• Do prolapse repair procedures such as cervicosacropexy or vaginosacropexy constitute an alternative surgical treatment option for urge and/or mixed urinary incontinence and concomitant apical prolapse? According to a systematic review of data collected from inception to 9/2021 (Page et al 2022), cure rates for mixed, urge urinary incontinence and apical prolapse were 47.5 % (CI95%:42.4-52.6), 73.8 % (CI95%:61.9-85.7) and 97-100 % respectively, at a mean follow-up of 9.7 ± 7.3 months. Additional incontinence surgery and concomitant or subsequent surgery for prolapse was performed in 38.9% (216/555) and 4.4% (13/299) women respectively. Cervicosacropexy or vaginosacropexy may remedy symptoms of urge and mixed urinary incontinence and seem to correct apical prolapse in the short term. Nevertheless, the overall level of evidence is low.

REFERENCES

Cui Y, Li Q, Wang D, Bao R, Li L, Zhu J, Li J, Li Z, Yin J, Zhou X, Yin H, Sun Z. Does electroacupuncture benefit mixed urinary incontinence? A systematic review and meta-analysis with trial sequential analysis. Int Urogynecol J. 2022; 33(4): 751-766.

Komar A, Bretschneider CE,  Mueller MG, Lewicky-Gaupp C, Collins S, Geynisman-Tan J, Tavathia M, Kenton K. Concurrent Retropubic Midurethral Sling and OnabotulinumtoxinA for Mixed Urinary Incontinence: A Randomized Controlled Trial. Obstet Gynecol. 2021; 137(1): 12-20.

Page AS, Page G, Deprest J. Cervicosacropexy or vaginosacropexy for urinary incontinence and apical prolapse: A systematic review. Eur J Obstet Gynecol Reprod Biol. 2022; 279: 60-71.

Sung VW, Borello-France D, Newman DK, Richter HE, Lukacz ES, Moalli P, Weidner AC, Smith AL, Dunivan G, Ridgeway B, Nguyen JN, Mazloomdoost D, Carper B, Gantz MG. Effect of Behavioral and Pelvic Floor Muscle Therapy Combined with Surgery vs Surgery Alone on Incontinence Symptoms Among Women with Mixed Urinary Incontinence: The ESTEEM Randomized Clinical Trial. JAMA. 2019; 322(11): 1066-1076.

Takahashi S, Mishima Y, Kuroishi K, Ukai M. Efficacy of mirabegron, a β(3) -adrenoreceptor agonist, in Japanese women with overactive bladder and either urgency urinary incontinence or mixed urinary incontinence: Post-hoc analysis of pooled data from two randomized, placebo-controlled, double-blind studies. Int J Urol. 2022; 29(1): 7-15.