A number of pharmacotherapies are available to treat overactive bladder (OAB) and reduce the negative effects it can have on quality of life [1, 2]. In addition to the efficacy and safety of therapies as determined in clinical trials, it is important to collect real world data in different geographies to assist physicians when making treatment decisions. Although several retrospective analyses using real world data on OAB pharmacotherapy persistence rates have been published along with real world data from prospective studies, few prospective registry data are available. This study in Taiwan and Korea aimed to characterize treatment patterns, including treatment discontinuation, switching to an alternative therapy, and persistence with therapies among adult patients diagnosed with OAB and initiating treatment in routine clinical practice. Additional aims included evaluating the effectiveness of OAB therapies, identifying factors associated with effectiveness and safety.

This was a prospective, longitudinal, multicenter, non-interventional, observational registry study (NCT03572231). The registry protocol was approved by the Institutional Review Board or Independent Ethics Committee at each site prior to enrolment. The study was conducted in accordance with the Declaration of Helsinki, Good Pharmacovigilance Practices issued by the International Society for Pharmacoepidemiology, the International Conference on Harmonization Good Clinical Practice Guidelines, and the Health Insurance Portability and Accountability Act (1996). All patients provided informed consent before contributing data to the registry. The study did not provide or recommend any treatment and all decisions were made by the treating physician following their usual clinical practices.
Male or female adult patients diagnosed with OAB for ≥3 months who were initiating monotherapy with either mirabegron or an antimuscarinic medication in routine clinical practice in Taiwan or Korea were eligible to participate. Exclusion criteria included receiving more than one therapy for OAB (including Chinese herbal medicine), previous surgery for OAB, treatment with onabotulinum toxin A, sacral neuromodulation, percutaneous tibial nerve stimulation, external beam radiation, stents, intermittent catheterization prior to or at time of enrolment, current participation in an OAB clinical trial, and mixed incontinence where stress incontinence is the predominant form. 
Data were collected at baseline, during physician visits at week 10–14 and week 22–26, and at any time when a decision to change the dose or formulation or to add another therapy, switch, or discontinue therapy was made (before weeks 22–26). No additional study visits, examinations, laboratory tests, or procedures were conducted as part of the study.
The primary endpoints were time from treatment initiation to discontinuation or switching to another OAB therapy or dose, and the proportion of patients who discontinued OAB treatment or switched to another treatment or dose within 183 days of initiating treatment, along with any reasons for discontinuation or switching. Key secondary endpoints included OAB symptom scores (OABSS) collected at baseline, the week 10–14 visit, the week 22–26 follow-up visit, when the physician and patient decided to change the dose or formulation or to discontinue therapy prior to the week 22–26 visit. Safety was assessed based on adverse events (AEs). Subgroup analysis by age (≤65 and >65 years) was an exploratory analysis.
The full analysis set included patients with data at baseline and ≥1 post-baseline visit. Safety was assessed in all patients who received ≥1 treatment dose. Time-to-event data were assessed using a Kaplan-Meier method. Patients without any treatment discontinuation, switching or dose change were considered as treatment persistent. Regression analyses adjusted for age, gender, previous medication, severity of OAB, type of OAB and comorbidity assessment score were used to identify factors associated with treatment discontinuation/switching and effectiveness.
Adverse events were recorded by the medication taken when the AE occurred. If more than one medication treatment overlapped with an AE, then the AE was counted under both treatments.

Enrolment of a total of 806 patients was initiated on 19 July 2018; 556 initiated treatment with mirabegron and 250 with an antimuscarinic. The safety analysis set comprised all enrolled patients. The full analysis set comprised 606 patients; 409 initiated mirabegron and 197 initiated antimuscarinics. Overall, the demographics and baseline characteristics were similar between the two groups. In the mirabegron-initiated group the mean age (SD) was 64.6 (12.82 years), 58.5% were female, 55.7% (306/549) were OAB-dry and 60.9% (333/547) had moderate OAB. The corresponding data for the antimuscarinics group were: 62.6 (13.94) mean age, 60.0% female, 51.6% (128/248) OAB-dry and 56.9% (141/248) with moderate OAB. A higher proportion of patients in the antimuscarinics group vs the mirabegron group had previously taken medication for OAB (39.6% vs 23.0%). In the antimuscarinics group, the most frequently initiated treatment was solifenacin succinate (66.0%).
The proportions of patients who discontinued treatment were 21.5% in the mirabegron and 19.8% in the antimuscarinics groups (Table 1). In the mirabegron group, 9.0% switched treatment and 1.0% changed the dose; in the antimuscarinics group, 16.2% switched treatment and 3.6% changed the dose. The most common reasons for discontinuing treatment in both groups were loss to follow-up and patient withdrawal. Based on univariate logistic regression analyses, significant factors for treatment discontinuation/switching included low baseline age, high severity of OAB and mild comorbidity score for the mirabegron group and female gender and no previous OAB medication for the antimuscarinics group. 68.5% of the mirabegron group and 60.4% of the antimuscarinics group had no treatment change within 183 days of treatment initiation. Persistence rates were higher in the mirabegron group than the antimuscarinics group at all reported time points, and at 183 days the persistence rate was higher in those aged >65 years than ≤65 years (Table 1). For both the mirabegron and antimuscarinics groups the median time from treatment initiation to discontinuation, switching, or dose change was not estimable as fewer than 50% of patients achieved these conditions. 
The mean (95% CI) change from baseline in OABSS score at week 10–14 was −1.9 (−2.2, −1.6) in the mirabegron and −1.7 (−2.2, −1.3) in the antimuscarinics groups, and at week 22–26, −2.3 (−2.7, −1.9) and −2.5 (−3.1, −2.0), respectively. Using generalized linear regression analysis, the statistically significant variable associated with change in OABSS score at week 22–26 was baseline OABSS score (p < 0.05 for both treatment groups). The observed AEs are shown in Table 2.

The proportion of patients who continued with treatment was higher in the mirabegron than the antimuscarinics group. There were higher persistence rates in the mirabegron than the antimuscarinics group at all time points and higher persistence rates in older than younger patients. The median time from treatment initiation to discontinuation, switching, or dose change was not estimable as over 50% of patients continued with treatment. For the secondary endpoints, patients in both groups demonstrated similar changes from baseline in OABSS score to week 10–14 and week 22–26, and baseline OABSS was the significant variable associated with change in OABSS score at week 22–26. Overall, the AE rates with mirabegron were about half of those reported in similar prospective registry studies conducted in different regions [1, 2].

These results provide meaningful insights for healthcare professionals when making decisions on initiating pharmacotherapy for the treatment of OAB.

Carlson KV, Rovner ES, Nair KV, Deal AS, Kristy RM, Schermer CR. Factors Associated with Improvements in Patient-Reported Outcomes During Mirabegron or Antimuscarinic Treatment of Overactive Bladder Syndrome: A Registry Study (PERSPECTIVE). Adv Ther. 2019 Aug;36(8):1906-1921.
Freeman R, Foley S, Rosa Arias J, Vicente E, Grill R, Kachlirova Z, Stari A, Huang M, Choudhury N. Mirabegron improves quality-of-life, treatment satisfaction, and persistence in patients with overactive bladder: a multi-center, non-interventional, real-world, 12-month study. Curr Med Res Opin. 2018 May;34(5):785-793.