Although oral antimuscarinics have been a mainstay of pharmacotherapy for the treatment of overactive bladder (OAB), persistence rates for continuing antimuscarinic therapy have been reported as low. Mirabegron, an oral selective beta-3 adrenoceptor agonist, has shown significantly improved persistence rates compared with antimuscarinics (1).
However, most studies on long-term persistence rates for OAB medications are based on retrospective analysis of medical and pharmaceutical claims databases, and are thus unable to determine the precise medical history of each patient, including the reason for treatment discontinuation. Furthermore, information on the follow-up status after discontinuation of therapy are typically not documented.
In this medical chart-based retrospective study, we aimed to identify a more comprehensive treatment profile of patients receiving OAB medication. Parameters of interest included time to and reasons for discontinuation or drug switching, treatment reinitiation, and post-discontinuation follow-up.

We retrospectively reviewed the medical charts of 777 patients aged ≥18 years who initiated antimuscarinic or beta-3 agonist therapy at our hospital between January 2014 and December 2016. Data on patient age, sex, chief complaint, and overactive bladder symptom score (OABSS) at initiation of therapy were collected. Persistence on treatment was assessed using two endpoints: median time to discontinuation and persistence rate at 12 months. 
For statistical analyses, nominal data were analyzed using Fisher’s exact test. Kaplan–Meier methods were used to estimate time to discontinuation and the log-rank test was used to compare between-group differences. Results were considered significant at p<0.05.

The median patient age was 74 years (interquartile range, 67–80 years), and 63% were male. The median follow-up time was 20 months. Chief complaints included increased urinary frequency (38%), nocturia (31%), urgency urinary incontinence (16%), urgency (8.5%), stress urinary incontinence (3.7%), and mixed urinary incontinence (1.8%). Antimuscarinics prescribed included solifenacin (53%), imidafenacin (30%), fesoterodine (10%), and propiverine (2%). Mirabegron was prescribed to 28% of the patients. As a result of drug switching or combination therapy, 79%,16%, 4%, and 1% of patients received one, two, three, and four medications during the study period, respectively. 

Overall and subgroup analyses of persistence are summarized in Table 1.
Persistence profiles were similar for the different antimuscarinics, and all antimuscarinics were subsequently evaluated as one combined group.
Male patients, older patients, and those with more severe symptoms (as indicated using OABSS question 3) were more likely to show persistence to OAB medications compared with other patients.
When all antimuscarinics combined were compared with mirabegron, treatment persistence with mirabegron was significantly longer than with antimuscarinics when given as either first- or second-line therapy (Table 1).

Reasons for discontinuation included unmet treatment expectations (37%), adverse effects (20%), and resolution of symptoms (16%). Discontinuation rates attributed to unmet treatment expectations, adverse effects, or resolution of symptoms did not differ significantly between antimuscarinics and mirabegron. 
Among the adverse effects which led to discontinuation or switching, the incidence of dry mouth was significantly higher for antimuscarinics than for mirabegron (23% vs 0%, p=0.005).

Of the 583 patients who discontinued medication, 41% were lost to follow-up and 59% continued with the visit schedule (Table 2). Of those who continued with the visit schedule, 32.3% continued with medication to treat lower urinary tract symptoms such as alpha-1 blockers, 5-alpha reductase inhibitors, phosphodiesterase-5 inhibitors, and herbal medicines. The overall reinitiation rate for OAB medication was 18.6%. Patients who discontinued OAB medication without resolution of symptoms, i.e. because of insufficient efficacy or tolerability, were significantly more likely to reinitiate OAB medication than those who discontinued OAB medication as a result of improvement (20.9% vs 10.5%, p=0.045). No patients proceeded to third-line therapy such as sacral neuromodulation, intradetrusor injection of onabotulinumtoxin A, or percutaneous tibial nerve stimulation.

Our results from the present retrospective real-world study at a regional general hospital are consistent with previous reports that used information from retrospective medical claims databases, in that long-term persistence of OAB medication is insufficient and that treatment persistence for mirabegron is significantly longer than that for antimuscarinics. The superior persistence of mirabegron was irrespective of the order of medication. Although antimuscarinic cycling was reported to be more frequent (2), the majority of patients (79%) in our study used only one medication during the study period. Also, the proportion of patients who received combination therapy with antimuscarinics and mirabegron was very low, and no patients received third-line therapy. This underutilization of further therapy could be attributable to health insurance limitations.
Patients with more severe symptoms at baseline were more likely to continue treatment for longer. However, those who discontinued medication because of resolution of symptoms were less likely to reinitiate treatment. Further investigation of this outcome could allow physicians to identify appropriate patients for medication therapy and avoid the administration of ineffective medications and drug-related adverse effects.

Although OAB medications are effective to some extent, persistent rates remain low. However, more than 80% of patients in the present study did not reinitiate OAB pharmacotherapy after discontinuation. Underutilization of third-line therapy was also reported. Considering the growing awareness in recent years of an association between anticholinergic use and increased risk of cognitive, physical, and functional impairment, administration of medications without sufficient consideration to potential side effects should be avoided, and cessation of medical treatment after a specific period of successful antimuscarinic or mirabegron therapy could be included in the clinical course of OAB treatment. Also, clinical models for appropriate patient selection and optimal treatment duration are needed.

Eur Urol 72: 389–399, 2017
Int Urol Nephrol 48:1029–1036, 2016