title: Safety and efficacy of flexible-dose fesoterodine in British subjects with overactive bladder: insights into factors associated with dose escalation.
abstract: OBJECTIVE
  This study evaluated the efficacy and safety of flexible-dose fesoterodine and factors associated with dose escalation in subjects with overactive bladder (OAB).
  
  
  METHODS
  In this 12-week, open-label study, 331 adults with OAB symptoms for ≥3 months, ≥8 micturitions and ≥3 urgency episodes per 24 h and who reported at least "some moderate" bladder-related problems were treated with fesoterodine 4 mg once daily for 4 weeks, with the option to escalate to 8 mg for the remaining 8 weeks based on discussion of efficacy and tolerability with the investigator. Factors influencing dose escalation were identified using stepwise logistic regression. Efficacy was assessed via 3-day bladder diaries and patient-reported outcomes.
  
  
  RESULTS
  Of the subjects, 59 % dose escalated at week 4; 93 % of escalators cited insufficient clinical response. The decision to escalate was most often made by the subject (alone or with the investigator). Improvements from baseline were observed in diary and patient-reported outcomes at weeks 4 and 12. Smaller improvements in micturition frequency and worse bladder-related problems at week 4 were significantly associated with increased likelihood of dose escalation; baseline micturition frequency, age, sex, body mass index, antimuscarinic-associated adverse events and OAB symptom duration were not. Non-escalators had greater improvement from baseline to week 4 than escalators; by week 12, improvement was similar among escalators and non-escalators. Fesoterodine was well tolerated.
  
  
  CONCLUSIONS
  Treatment with flexible-dose fesoterodine improved bladder diary and patient-reported outcomes. Lower clinical response was related to dose escalation; after escalation, response in escalators approached that of non-escalators.
authors.affiliation: King's College Hospital, 8 Devonshire Place, London, W1G 6HP, UK. linda@lindacardozo.co.uk
authors.forename: Linda
authors.initials: L
authors.lastname: Cardozo
authors.forename: Timothy
authors.initials: T
authors.lastname: Hall
authors.forename: John
authors.initials: J
authors.lastname: Ryan
authors.forename: Caty
authors.initials: C
authors.lastname: Ebel Bitoun
authors.forename: Imran
authors.initials: I
authors.lastname: Kausar
authors.forename: Amanda
authors.initials: A
authors.lastname: Darekar
authors.forename: Adrian
authors.initials: A
authors.lastname: Wagg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001559:Benzhydryl Compounds / Q000009:adverse effects* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000009:adverse effects* / Q000627:therapeutic use*; D016896:Treatment Outcome; D006113:United Kingdom / Q000453:epidemiology; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000453:epidemiology; D053202:Urinary Incontinence, Urge / Q000453:epidemiology
chemical_list: D001559:Benzhydryl Compounds; D018727:Muscarinic Antagonists; C526675:fesoterodine