Patient-optimized doses of fesoterodine improve bladder symptoms in an open-label, flexible-dose study.

ABSTRACT

OBJECTIVE: To assess changes in overactive bladder (OAB) symptoms and patient-reported outcomes in a post hoc analysis in which subjects from a 12-week, open-label, flexible-dose fesoterodine study were stratified according to whether they opted for dose escalation. PATIENTS AND METHODS: Subjects with OAB (eight or more micturitions and three or more urgency episodes per 24 h) who reported dissatisfaction with tolterodine within 2 years of screening received fesoterodine 4 mg once daily for 4 weeks, with an optional dose increase to 8 mg after week 4 based on discussion of efficacy and tolerability between the subject and investigator. Subjects completed 5-day diaries, the Patient Perception of Bladder Condition (PPBC) and Urgency Perception Scale (UPS) at baseline and weeks 4 and 12, and the Overactive Bladder Questionnaire (OAB-q) at baseline and week 12. Subjects rated treatment satisfaction at week 12. RESULTS: Dose escalation to 8 mg at week 4 was chosen by 255 (50%) of 513 subjects. At baseline, subjects who opted for dose escalation at week 4 (escalators) had significantly higher means for all diary variables except urgency urinary incontinence (UUI) episodes, significantly greater OAB-q Symptom Bother scores and significantly lower OAB-q health-related quality of life (HRQL) scores (all P < 0.05) compared to subjects who did not opt for dose escalation (non-escalators). There was no significant difference in the percentage of escalators (51%) and non-escalators (48%) who reported at least one UUI episode on baseline diary. At week 4 (before the decision to escalate was made), all outcomes were significantly improved vs baseline among both groups (all P < 0.0001), although non-escalators had significantly greater improvements in all diary variables and in PPBC and UPS scores than escalators (all P < 0.05), and the 5-day diary-dry rate (i.e. the percentage of subjects with at least one UUI episode on baseline diary and no UUI episodes on week 4 diary) was significantly higher (P = 0.0016) among non-escalators (62%) than among escalators (42%). At week 12, all outcomes were again significantly improved vs baseline among both groups (all P < 0.0001). There were no significant differences between non-escalators and escalators in week 12 improvements for most diary variables, UPS scores, OAB-q Symptom Bother scores, the diary-dry rate (68% vs 60%) or the percentage of subjects who reported treatment satisfaction (82% vs 78%). However, escalators still had significantly greater improvements from baseline in urgency episodes, PPBC scores and OAB-q total HRQL and Coping domains (P < 0.05). Adverse event rates were similar between non-escalators and escalators. Dry mouth was the most frequently reported adverse event; most cases were mild. CONCLUSION: Flexible-dose fesoterodine significantly improved OAB symptoms and patient-reported outcomes in subjects who chose to remain on the initial 4-mg dose, as well as in the 50% of subjects who escalated to the 8-mg dose after 4 weeks. Non-escalators had significantly fewer OAB symptoms at baseline and significantly greater improvements than escalators before dose escalation. Escalators showed increased symptom relief after dose escalation; improvements in most outcomes were similar among non-escalators and escalators by week 12. Flexible-dose fesoterodine was well tolerated, with similar adverse-event profiles observed in the escalator and non-escalator groups. These results may help clinicians to identify patients more likely to require fesoterodine 8 mg to achieve maximum relief of OAB symptoms and thus facilitate dose escalation in these patients.