Superior efficacy of fesoterodine over tolterodine extended release with rapid onset: a prospective, head‐to‐head, placebo‐controlled trial

Abstract

placebo on UUI episodes (primary endpoint), micturitions, urgency and most other diary endpoints, and on the PPBC, UPS and all OAB Questionnaire scales and domains (all P < 0.05).• Superiority of fesoterodine 8 mg over tolterodine ER 4 mg was seen as early as week 4 (3 weeks after escalation to fesoterodine 8 mg). At week 1, fesoterodine 4 mg was superior to placebo on most diary variables, the PPBC and the UPS (all P < 0.05). Dry mouth and constipation rates were 28% and 4% with fesoterodine, 13% and 3% with tolterodine ER, and 5% and 2% with placebo.• Discontinuation rates as a result of adverse events were 5%, 3% and 2% for fesoterodine, tolterodine ER and placebo, respectively. CONCLUSIONS• In this randomized study, which is the largest to compare antimuscarinic efficacy performed to date, fesoterodine 8 mg was superior to tolterodine ER 4 mg for UUI episodes, micturitions and urgency episodes, as well as for self-reported patient assessments of bladder-related problems, urgency, symptom bother and health-related quality of life.• The superiority of fesoterodine 8 mg over tolterodine ER 4 mg was observed as early as 3 weeks after escalation from fesoterodine 4 mg for most outcomes. These data may have important implications for the clinical management of OAB patients previously treated with tolterodine ER. KEYWORDSantimuscarinic, fesoterodine, tolterodine, head-to-head, efficacy, quality of life What's known on the subject? and What does the study add? A previous trial found greater efficacy with the maximum available dose of fesoterodine 8 mg compared with the maximum available dose of tolterodine ER 4 mg and placebo for improving overactive bladder symptoms, and patient-reported outcomes were demonstrated by a recent placebo-controlled, head-to-head trial.The results of this trial, the largest to date to compare antimuscarinic efficacy, confirms the superior efficacy of fesoterodine 8 mg over tolterodine ER 4 mg for the treatment of OAB symptoms, and further emphasize the clinical advantage of the availability of an additional 8-mg dose over single-dose tolterodine ER 4 mg. Study Type -Therapy (RCT) Level of Evidence 1b OBJECTIVE• To show the superior efficacy of fesoterodine over tolterodine extended release (ER) in a placebo-controlled overactive bladder (OAB) trial with predefined treatment comparisons for both diary measures and patient-reported outcomes. MATERIALS AND METHODS• In this 12-week, double-blind, doubledummy trial, subjects reporting > 1 urgency urinary incontinence (UUI) episode and ≥ 8 micturitions per 24 h at baseline were randomized to fesoterodine (4 mg for 1 week, 8 mg for 11 weeks), tolterodine ER 4 mg, or placebo.• Subjects completed 3-day bladder diaries, the Patient Perception of Bladder Condition (PPBC) and the Urgency Perception Scale (UPS) at baseline and weeks 1, 4 and 12 and the OAB Questionnaire at baseline and week 12. RESULTS• A total of 2417 subjects were randomized. At week 12, fesoterodine 8 mg showed superiority over tolterodine ER 4 mg and

Flexible‐Dose Fesoterodine in Elderly Adults with Overactive Bladder: Results of the Randomized, Double‐Blind, Placebo‐Controlled Study of Fesoterodine in an Aging Population Trial

“…The number of participants who required catheterization (n = 3, 0.8% vs n = 1, 0.3%) and the number who discontinued the study because of urinary retention (n = 4, 1.0% vs n = 1, 0.3%) were also higher with fesoterodine than placebo. The overall discontinuation rates in the fesoterodine (19.9%) and placebo (13.2%) groups in the present study were at the high end of the range of discontinuation rates observed in fesoterodine (10-21%) and placebo (9-15%) arms of trials conducted in younger participants; 18,19,34,35 discontinuation rates in the present study were slightly higher in participants older than 75 in both treatment groups.…”

Summary of Anticholinergic Pharmacotherapy Available for Overactive Bladder

“…Again, fesoterodine was superior to tolterodine ER in reducing mean daily UUI episodes (P00.0072), micturitions (P0 0.0016), urgency (P<0.0001), and other secondary end points. Likewise, fesoterodine had a higher incidence of dry mouth (28%, 13%, and 5% with fesoterodine, tolterodine, and placebo, respectively), although AE-related discontinuation rates were comparable [44].…”

“…Two studies have compared fesoterodine with tolterodine [43,44]. In a double-blind RCT comparing fesoterodine (4-mg dose for 1 week, then 8 mg for 11 weeks), tolterodine ER (4 mg), and placebo, fesoterodine (8 mg) significantly decreased mean daily UUI episodes after 12 weeks more than tolterodine ER (-1.72 vs -1.61; P<0.05) and placebo (-1.72 vs -1.46; P<0.005) [43].…”

“…This was met with a higher incidence of dry mouth in fesoterodine than in tolterodine (28% vs 16%; no P value given) but similar AE-related discontinuation rates (6% vs 4%) [43]. Kaplan et al [44] published their results from the largest double-blind RCT again comparing fesoterodine, 8 mg, with tolterodine ER, 4 mg, in 2,417 patients. Again, fesoterodine was superior to tolterodine ER in reducing mean daily UUI episodes (P00.0072), micturitions (P0 0.0016), urgency (P<0.0001), and other secondary end points.…”

Medication-Induced Dry Mouth

“…Oxybutynin, tolterodine, trospium, solifenacin, darifenacin and fesoterodine are muscarinic receptor antagonists commonly used in the treatment of overactive bladder, and each of these drugs blocks M3 and/or M2 receptors, which are the intended targets since the latter mediate smooth muscle relaxation in the bladder. Dry mouth is an ADR of varying severity depending on the drug; for example, tolterodine appears to produces less dry mouth than fesoterodine although each drug interacts with a number of muscarinic receptors including M3 ( [ 53 ], [ 54 ], [ 55 ], [ 56 ]). Studies on the mouse have compared some prescribed anticholinergics used in the treatment of overactive bladders -oxybutynin, solifenacin and tolterodine.…”