Add-on fesoterodine for residual storage symptoms suggestive of overactive bladder in men receiving a-blocker treatment for lower urinary tract symptoms

Study Type Therapy (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Male lower urinary tract symptoms are often attributed to bladder outlet obstruction secondary to benign prostatic hyperplasia and treated with drugs targeting the prostate. However, many men with storage lower urinary tract symptoms may not respond adequately to these agents. Antimuscarinics, with or without an a-blocker, may be effective for the treatment of the storage symptoms of overactive bladder in some men. Flexible-dose fesoterodine as an add-on treatment significantly improved urinary frequency and symptom bother, but not urgency episodes (primary endpoint), versus add-on placebo and was well tolerated in men with persistent overactive bladder symptoms despite receiving a-blocker. OBJECTIVE To evaluate flexible-dose fesoterodine vs placebo in men with persistent overactive bladder (OAB) symptoms despite receiving a-blocker treatment SUBJECTS AND METHODS This was a double-blind, 12-week, flexible-dose trial. Men with persistent storage symptoms (=8 micturitions and =3 urgency episodes per 24 h) after receiving an a-blocker for =6 weeks were randomized to add-on fesoterodine 4 mg or placebo, with optional dose escalation to 8 mg at week 4 and reduction back to 4 mg at week 8 (or matching placebo adjustments). Subjects completed 3-day diaries, International Prostate Symptom Score (IPSS), Overactive Bladder Questionnaire (OAB-q), Patient Perception of Bladder Condition (PPBC), and Urgency Perception Scale (UPS) at baseline and weeks 4 and 12. RESULTS A total of 943 men were randomized and received at least one dose of study treatment (fesoterodine, n= 471; placebo, n= 472). Among these, 251 (53%) in the fesoterodine group and 300 (64%) in the placebo group requested dose escalation at week 4 and 35 (7%) and 15 (3%) requested dose reduction at week 8. Changes from baseline to week 12 in urgency episodes (primary endpoint) in the fesoterodine (-3.2) and placebo (-2.9) groups were not significantly different (P= 0.196), but improvements in micturitions (P= 0.009) and OAB-q symptom bother score (P= 0.007) were significantly greater with fesoterodine. At week 4, significantly greater improvements in micturitions (P= 0.006), severe urgency episodes (P= 0.006), IPSS storage score (P= 0.022), OAB-q symptom bother score (P= 0.004), and OAB-q health-related quality of life (P= 0.041), but not urgency episodes (P= 0.062), were observed with add-on fesoterodine. Dry mouth (fesoterodine, 21%; placebo, 6%) and constipation (fesoterodine, 6%; placebo, 2%) were the most common adverse events. Dysuria and urinary retention were reported by 3% and 2% of subjects, respectively, in the fesoterodine add-on group vs 1% and <1% of subjects, respectively in the placebo add-on group. One subject in each group had acute urinary retention requiring catheterization. CONCLUSIONS Flexible-dose fesoterodine was well tolerated as an add-on treatment in men with persistent storage symptoms. Changes in urgency episodes at week 12 (primary endpoint) and many secondary endpoints were not significantly different between fesoterodine and placebo add-on treatment; however, improvements in frequency and symptom bother were significantly greater with fesoterodine. These data suggest that there remains a limited understanding of the optimal evaluation and treatment of men with LUTS.