Treatment Patterns with Mirabegron and Antimuscarinics for Overactive Bladder: A Prospective, Registry Study in Taiwan and South Korea (FAITH)

FAITH is the first multinational study from Asia to record registry data prospectively from primary sources; it complements the clinical practice data from prospective registries involving patients with OAB in other geographies, such as BELIEVE (Europe) [12] and a Prospective, non-intErventional Registry Study of PatiEnts initiating a Course of drug Therapy for overactIVE bladder (PERSPECTIVE; North America) [15]. Studies conducted within the clinic assessing patient-reported outcomes in OAB offer insight into the elements of care important to patients and factors that may impact treatment persistence. In particular, HRQoL and treatment satisfaction can be key to optimizing persistence [12].

These data show that 68.5% of the mirabegron initiator group and 60.4% of the antimuscarinics initiator group did not change or discontinue treatment. Hence, the median time from treatment initiation to discontinuation, switching, or dose change was not estimable in either group. Persistence rates at 50 and 183 days were 91.0% and 67.4%, respectively, in the mirabegron initiator group and 85.8% and 56.9%, respectively, in the antimuscarinics initiator group. In addition, persistence was greater in older patients in both groups. These persistence data were similar to other prospective observational studies in Japanese and European populations. In a prospective post-marketing study in Japan (n = 1139), persistence with mirabegron was 77.6% at 6 months and 66.0% at 1 year [11]. A large, prospective European non-interventional study (n = 796) reported 53.8% persistence with mirabegron after a 10–12-month follow-up [12]. In addition, smaller country-specific studies reported 1-year persistence rates of 25–71% with mirabegron [16, 17]. One possible explanation for the relatively small difference in persistence and switching rates for mirabegron and antimuscarinics in our study is its design, because treatment decisions were made by the investigator rather than being randomly assigned. It is possible, therefore, that patients who previously experienced AEs with antimuscarinics were prescribed mirabegron. Persistence rates could also have been influenced by differences in healthcare systems between regions, including the cost of the drug for the patient.

The current study was not randomized or designed to compare treatments. However, a number of comparative studies have demonstrated improved persistence with mirabegron over antimuscarinics. In a prospective, open-label, 48-month observational study in Taiwan, 171 patients who switched from solifenacin to mirabegron because of continuing OAB symptoms remained on therapy for significantly longer vs. the overall group that had started on solifenacin (n = 416) [13]. Retrospective analyses of US and Canadian insurance claims databases demonstrated that median persistence was 90 days with mirabegron vs. 30 days with tolterodine [8]; discontinuation or switching occurred in 81% of patients receiving mirabegron vs. 88% receiving anticholinergics [9]; and 12-month persistence rates were 31.7% vs. 13.8–22.0% with mirabegron vs. antimuscarinics, respectively [18]. A retrospective analysis of two Japanese databases showed that median persistence with mirabegron vs. the antimuscarinic comparators was 44 vs. 21–30 days (insurance claims), respectively, and 105 vs. 62–84 days, respectively (pharmacy claims) [10]. Finally, a US screening survey found that 25% of respondents discontinued antimuscarinic treatment over a 12-month period, predominately as a result of a lack of efficacy or switching to a new medication [19].

Regarding secondary endpoints, patients in both treatment groups demonstrated similar changes from baseline in OABSS, and higher baseline OABSS was significantly associated with greater improvement in OABSS at week 22–26. Furthermore, patients in both treatment groups indicated improvement based on OAB-Q-SF, OAB-Q-SF HRQoL, and OAB-BAT scores. This is the first registry study to use the OAB-BAT, a new tool developed by a global advisory board for assessing patient-reported outcomes in OAB, which may become an alternative to bladder diaries and other patient-reported outcome measures [14]. HCRU was low across all measures for both treatment groups, in line with other studies of mirabegron [12].

In this study, the most commonly reported AE was UTI in the mirabegron treatment period and dry mouth in the antimuscarinics period. UTI, urinary retention, cardiac disorders, and increased blood pressure have been reported previously with mirabegron [6], whereas dry mouth and constipation are associated with antimuscarinics as a result of their anticholinergic effects. Anticholinergic effects are bothersome and can be concerning in older patients [20]. One explanation for the generally low incidence of dry mouth in the antimuscarinics group in this study may be that the majority were taking solifenacin, which has a lower rate of dry mouth than other antimuscarinics. The rate of UTIs was 3.3% in the antimuscarinics group and 2.5% in the mirabegron group. The overall rates of AEs were 21.6% and 17.4%, respectively, which are consistent with other reports [7, 20]. However, the overall AE rate with mirabegron in this study was about half that reported for other prospective registry studies (BELIEVE [42.8%] and PERSPECTIVE [33.1%]) [12, 15]. As these AE data reflect experiences in clinical practice, they provide valuable insight for HCPs. The “cardiac failure acute” SAE, assessed to be drug related by the investigator, was evaluated as not drug related by the sponsor and was attributed to concomitant disease. The term “cardiac failure acute” was likely selected as being closest to describing the event, but no causal relationship could be established in this non-interventional study.

Additional analyses found that patients were more likely to continue treatment if they were older (at baseline) and had mild OAB (mirabegron) or were male and had previously received OAB medication (antimuscarinics). These findings are in line with other previous persistence investigations, which have typically found that older and treatment-experienced patients persist with OAB medication for a longer period of time than younger and treatment-naïve patients [8, 10, 21‐23]. Furthermore, some studies that have also been conducted in East Asia have found that male patients persist with treatment longer than female patients [10, 22]. Older and treatment-experienced patients may be willing to persist with treatment as they may have experienced the condition for a longer duration and might be more familiar with the benefit–risk profile of OAB therapies. In addition, AEs could be a factor associated with these findings based on the safety profile and known mechanisms of action. The safety profile of mirabegron in older patients has been established [24], with rates of dry mouth and constipation being lower than with antimuscarinics [7]. Furthermore, mirabegron does not affect cognition [25] or have an association with dementia [26], potentially because it does not have the anticholinergic burden associated with antimuscarinics [27]. Similarly, mirabegron can be considered for patients with comorbidities owing to a neutral risk for cardiac events [28] and a lower risk of urinary retention [29].

Because this registry study was an observational clinical practice investigation, some possible sources of bias may have been linked to patient selection and recall error as a result of patient self-reporting. Potential selection bias arising from a lack of complete enrollment of potentially eligible patients was reduced by maintaining screening logs at the sites. Other limitations are the relatively short duration of follow-up and the high proportion of patients lost to follow-up. Finally, the study was not randomized or designed for comparison, and results were not adjusted for any baseline characteristics. This means any perceived differences between treatment groups may be attributed to other confounders and not to treatment effects.