title: Persistence, adherence, and switch rates among extended-release and immediate-release overactive bladder medications in a regional managed care plan.
abstract: BACKGROUND
  Pharmacotherapy constitutes an important adjunct to behavioral therapy for the treatment of overactive bladder (OAB). Tolterodine and oxybutynin are commonly prescribed drugs for OAB treatment that exert their beneficial effect by suppressing bladder muscle contractions. However, high discontinuation rates have been observed for these drugs in clinical trials, as well as in real-world settings, in part due to adverse effects. Extended-release (ER) formulations were introduced with an improved tolerability profile over immediate-release (IR) versions of the 2 drugs. No study has compared persistence and adherence to therapy for both the ER and IR versions of tolterodine and oxybutynin.
  
  
  OBJECTIVE
  To compare persistence, adherence, and switch rates for the IR and ER formulations of oxybutynin and tolterodine for patients enrolled in a regional managed care plan.
  
  
  METHODS
  Study patients were adults (aged e 18 years), with at least 1 pharmacy claim for either tolterodine extended-release (tol-ER), oxybutynin extended-release (oxy-ER), tolterodine immediate-release (tol-IR), or oxybutynin immediate-release (oxy-IR) during the period from July 1, 1999, to December 31, 2003, and were continuously eligible for benefits from 6 months before through 12 months after the initial OAB pharmacy claim (index) date. A retrospective cohort study design was used following patients from the index date to the occurrence of non-persistence with the index medication (i.e., a gap of > 45 days between successive prescription fills or a switch to any other OAB medication), or the end of a 1-year follow-up period, through December 31, 2004. Switching was defined as any change from the index medication, including a change in dose form (e.g., tol-IR to tol-ER), to one of the other 3 study drugs, or to a different OAB treatment (e.g., trospium chloride, oxybutynin patch, flavoxate, hyoscyamine sulfate, or propantheline bromide) during the follow-up period. Adherence was measured as the proportion of patients with a medication possession ratio (MPR) of at least 80%. MPR was calculated as (1) the sum of days supply for all pharmacy claims except the last pharmacy claim, divided by (2) the total number of days from the first fill date to the fill date of the last pharmacy claim. The association of drug therapy with study outcomes was assessed with bivariate and adjusted (multivariate) analyses. Multivariate analyses controlled for demographic and clinical characteristics, plan type, patient out-of-pocket cost for the index medication, and year of therapy initiation.
  
  
  RESULTS
  1,117 patients had at least 1 pharmacy claim for an OAB study drug (n = 454 for tol-ER [40.6%], n = 249 for oxy-ER [22.3%], n = 306 for tol-IR [27.4%], n = 108 for oxy-IR [9.7%]), of whom 81.6% were women. The mean (standard deviation [SD]) age of the study population was 55.7 (14.5) years. Only 53.7% had at least 1 OAB diagnosis recorded during the 18-month eligibility period. 44.5% of patients did not have a refill after the initial (index) pharmacy claim (39.4% for oxy-ER, 42.7% for tol-ER, 46.1% for tol-IR, and 59.3% for oxy-IR; P = 0.004). Only 13.2% persisted with treatment for at least 1 year (tol-ER = 15.0%, oxy-ER = 15.3%, tol-IR = 11.4%, oxy-IR = 6.5%; P = 0.050). The median days to discontinuation (non-persistency) were 31.0 overall, 33.0 for tol-ER, 34.0 for oxy-ER, 32.0 for tol-IR, and 0 for oxy-IR; P = 0.010. The overall switch rate as a percentage of all study patients was 13.3%, ranging from 9.9% for tol-ER, 13.7% for tol-IR, 16.5% for oxy-ER, and 19.4% for oxy-IR; P = 0.020. Of patients who refilled their initial prescription at least once, 24.0% made a medication switch. Adherence rates as measured by percentage of patients with MPR >or= 80% were 30.3% overall and higher for the ER formulations: 35.2% for tol-ER, 36.1% for oxy-ER, 23.5% for tol-IR, and 14.8% for oxy-IR; P < 0.001.
  
  
  CONCLUSIONS
  Adherence was significantly better for ER than IR agents. The high rate of non-persistence (44.5%) following the first (index) prescription highlights the need for medication counseling by health care professionals.
authors.affiliation: Xcenda, LLC, Cincinnati, OH 45255, USA. anna.dsouza @xcenda.com
authors.forename: Anna O
authors.initials: AO
authors.lastname: D'Souza
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Smith
authors.forename: Lesley-Ann
authors.initials: LA
authors.lastname: Miller
authors.forename: Joseph
authors.initials: J
authors.lastname: Doyle
authors.forename: Rinat
authors.initials: R
authors.lastname: Ariely
mesh_terms: D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D015331:Cohort Studies; D003408:Cresols / Q000008:administration & dosage / Q000627:therapeutic use*; D016208:Databases, Factual; D003692:Delayed-Action Preparations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008329:Managed Care Programs; D008333:Mandelic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D015999:Multivariate Analysis; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D010349:Patient Compliance / Q000706:statistics & numerical data; D010665:Phenylpropanolamine / Q000008:administration & dosage / Q000627:therapeutic use*; D012189:Retrospective Studies; D000068737:Tolterodine Tartrate; D016312:Treatment Refusal / Q000706:statistics & numerical data; D014481:United States; D053201:Urinary Bladder, Overactive / Q000188:drug therapy*
chemical_list: D001559:Benzhydryl Compounds; D003408:Cresols; D003692:Delayed-Action Preparations; D008333:Mandelic Acids; D018727:Muscarinic Antagonists; D010665:Phenylpropanolamine; D000068737:Tolterodine Tartrate; C005419:oxybutynin