title: One-year investigator-blind randomized multicenter trial comparing Asacol 2.4 g once daily with 800 mg three times daily for maintenance of remission in ulcerative colitis.
abstract: BACKGROUND
  Mesalazine (Asacol) is still widely prescribed in divided doses for ulcerative colitis (UC), despite evidence that adherence is improved by once-daily (OD) prescribing. We aimed to investigate whether OD Asacol was as effective as three times (TDS) daily dosing, and to evaluate the role of treatment adherence.
  
  
  METHODS
  An investigator-blind randomized trial was undertaken comparing OD Asacol (three 800 mg tablets) versus one 800 mg TDS in maintenance of remission of UC over 1 year. The primary endpoint was relapse rate, and noninferiority would be concluded if the lower limit of the two-sided 95% confidence interval (CI) of the difference in proportions relapsing (TDS-OD) exceeded -10%. Adherence was measured by tablet counts and self-reported adherence. A subgroup of patients used a bottle cap that recorded all bottle opening events.
  
  
  RESULTS
  In all, 213 patients were randomized. In the intention-to-treat (ITT) population, relapse rates were 31% (95% CI 22%-40%) in the OD and 45% (95% CI 35%-54%) in the TDS group. Primary analysis confirmed the noninferiority of OD dosing. Two of the study populations, ITT and per-protocol (PP), showed potential superiority of OD dosing. All measures of adherence showed that it was significantly better in the OD group. Multivariate analysis, however, showed OD dosing was associated with lower relapse risk independently of adherence.
  
  
  CONCLUSIONS
  OD dosing with Asacol 2.4 g is as safe and effective as TDS dosing, and secondary analysis confirmed significantly reduced relapse rates. The benefit, however, was clinically borderline and may relate in part to ease of adherence.
authors.affiliation: Department of Medicine, University Hospital of Wales, Cardiff, UK. Barney.hawthorne@wales.nhs.uk
authors.forename: A Barney
authors.initials: AB
authors.lastname: Hawthorne
authors.forename: Rachel
authors.initials: R
authors.lastname: Stenson
authors.forename: David
authors.initials: D
authors.lastname: Gillespie
authors.forename: Edwin T
authors.initials: ET
authors.lastname: Swarbrick
authors.forename: Anjan
authors.initials: A
authors.lastname: Dhar
authors.forename: Kapil C
authors.initials: KC
authors.lastname: Kapur
authors.forename: Kerry
authors.initials: K
authors.lastname: Hood
authors.forename: Chris S J
authors.initials: CS
authors.lastname: Probert
mesh_terms: D000284:Administration, Oral; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D055118:Medication Adherence; D019804:Mesalamine / Q000008:administration & dosage*; D008875:Middle Aged; D011379:Prognosis; D012074:Remission Induction; D012108:Research Personnel; D016037:Single-Blind Method; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019804:Mesalamine
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