Efficacy of mirabegron, a β₃‐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

Abstract

To confirm if mirabegron 50 mg shows efficacy in women with overactive bladder and either urgency urinary incontinence or mixed urinary incontinence versus placebo. Methods: Post-hoc analyses were carried out using pooled data from a Japanese phase IIb and a phase III study. The primary efficacy end-point was baseline to end-oftreatment change in the mean number of micturitions/24 h. The secondary end-points were changes in the mean voided volume/micturition, mean number of urgency and incontinence episodes/24 h, and mean number of nocturia episodes/night. Other endpoints were quality of life and incontinence normalization rates. Results: Women with urgency urinary incontinence (placebo n = 204, mirabegron n = 214) and mixed urinary incontinence (placebo n = 122, mirabegron n = 139) were included. Change in mean micturitions/24 h at end-of-treatment for mirabegron was statistically significant versus placebo in both populations; the effect size increased over time. For all secondary end-points, 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. 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. Conclusions: Mirabegron 50 mg significantly improved key overactive bladder symptoms versus placebo in women with urgency urinary incontinence, and it also improved most overactive bladder symptoms, including micturition frequency, in patients with mixed urinary incontinence. These findings support the benefits of using mirabegron in the female overactive bladder wet population.

Editorial Comment to Efficacy of mirabegron, a β3‐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

“…In the present study, a post hoc analysis of pooled data from two randomized, placebo-controlled, double-blind studies, Takahashi et al 1 concluded that mirabegron is effective in patients with "OAB-wet", including those with UUI or mixed urinary incontinence (MUI). The two randomized studies included women predominantly (approximately 80%), therefore, evidence in men with OAB/benign prostatic hyperplasia is still required.…”

“…In the present study, a post hoc analysis of pooled data from two randomized, placebo‐controlled, double‐blind studies, Takahashi et al 1 . concluded that mirabegron is effective in patients with “OAB‐wet”, including those with UUI or mixed urinary incontinence (MUI).…”

Mirabegron attenuates porcine ureteral contractility via α1-adrenoceptor antagonism

“…Additionally, previous studies have shown that the proximal and distal sections of the ureter respond pharmacologically differently (Lim et al 2020 ), and that receptor distribution changes throughout the length of the ureter (Itoh et al 2007 ). Furthermore, previous studies that have reported a relaxatory effect of β 3 -adrenoceptor activation by mirabegron in smooth muscles of the urinary tract have mainly addressed contractions that are tonic in nature (Svalo et al 2013 ; Takasu et al 2007 ) and the role of β-adrenoceptors in phasic contractions is still underrepresented in the literature.…”

“…The use of a β 3 -adrenoceptor agonist mirabegron for the management of overactive bladder has been shown to be effective in the recent years, reducing both urinary frequency and urgency, with low incidence of side effects and thus, high tolerability profile (Takahashi et al 2022 ). Mirabegron is proposed to function by activating the β 3 -adrenoceptors in the human detrusor smooth muscle, inducing a relaxation during the storage phase of micturition (Svalo et al 2013 ; Takasu et al 2007 ). Previous studies have also shown that mirabegron is capable of relaxing other smooth muscle tissues of the urinary tract like the urethra and the prostate (Alexandre et al 2016 ; Huang et al 2021 ).…”

Mirabegron in the Management of Overactive Bladder Syndrome

“…In a post hoc analysis of pooled data from two of these earlier studies, Takahashi et al substantiated the use of mirabegron in OAB wet populations, illustrating a statistically significant improvement in mean micturitions/24h and incontinence episodes at EoT, as well as other secondary endpoints, for women with urgency urinary incontinence or mixed urinary incontinence. 50 …”