Posterior Tibial Nerve Stimulation With versus Without Mirabegron in Women with Refractory UUI

Objectives: To compare change in urgency urinary incontinence episodes (UUIEs) in women undergoing posterior tibial nerve stimulation (PTNS) plus mirabegron versus PTNS plus placebo for treatment of refractory urgency urinary incontinence (UUI) and OAB-wet symptoms.

Methods: A randomized controlled clinical trial was performed in individuals identifying as female > 18 years old with UUI and OAB-wet symptoms refractory to second-line treatment or who could not tolerate anticholinergic medications. Institutional Review Board approval was obtained and participants provided written informed consent. Both participants and providers were blinded to treatment allocation. Participants were randomized (1:1) to either PTNS plus mirabegron or PTNS plus placebo. Participants completed a 3-day bladder diary prior (baseline) to and post 12-week treatment of PTNS. Additionally, validated subjective symptom distress and impact questionnaires were obtained pre- and post-treatment. The primary outcome was a comparison of change in number of UUIEs over a 3-day bladder diary pre- vs. post-treatment between arms. Secondary outcomes included urinary frequency, stress UIEs (SUIEs), nocturia, and total pad count on the 3-day bladder diary in addition to subjective outcomes measured by the Urogenital Distress Inventory (UDI-6), Overactive Bladder Questionnaire-Short Form (OAB-q SF), Incontinence Impact Questionnaire Short Form (IIQ-7) questionnaires, as well as adverse events. Comorbidities were assessed with the Charlson Comorbidity Index (CCI) and pain catastrophizing (PC) using the PC Scale. The primary outcome was analyzed via sample t tests; Chi-square tests or Fisher’s exact tests were used for categorical variables, and paired t-tests (intra-arm) for continuous variables were used as appropriate. Analysis was per protocol including all women providing 12-week outcome data. A significance level was set at 0.05.

Results: Fifty-four subjects were randomized with mean±SD baseline age 56.2 ± 15.6 and baseline BMI 35.0 ± 9.4 (kg/m²); no differences noted in any clinical-demographic characteristics. Eight subjects (7 mirabegron, 1 placebo) did not complete the 12-week PTNS treatment. There was a significant difference between arms in changes pre/post-treatment UUIEs, 9.4±3.9, mirebegron versus 5.3±5.5, placebo, p=0.007. Significant differences were found pre/post-treatment in urinary frequency, change in OABq SF Symptom Bother score, and in the OABq SF Symptom HRQL score. No significant differences were noted for other secondary outcomes (Table). 90.0% of subjects in the mirabegron arm had >50% reduction in UUI episodes compared to 23.1% in the placebo arm (Figure). Adverse events included 3 patients in each arm who experienced UTIs and 3 patients in each arm who experienced transient leg swelling. All patients who reported adverse events completed the full 12-week PTNS treatment protocol.

Conclusions: In subjects undergoing PTNS treatment for refractory UUI and OAB-wet symptoms, the addition of the β-3 agonist mirabegron produced significant improvement in both objective and subjective irritative bladder outcomes compared to PTNS plus placebo.