title: The optimal dose of 5-aminosalicylic acid in active ulcerative colitis: a dose-finding study with newly developed mesalamine.
abstract: OBJECTIVE
  5-Aminosalicylate is the gold standard for inducing remission in patients with mildly to moderately active ulcerative colitis. The optimal dose is as yet not defined. Despite some recent developments, the ideal formulation for 5-aminosalicylic acid is still awaited. A new pellet preparation was designed combining slow and delayed release properties. Aims of the study were to find the optimal dose and to test efficacy and safety of a new 5-aminosalicylic acid formulation.
  
  
  METHODS
  Three hundred twenty-one patients were included in a double-blind multicenter trial. Inclusion criteria were active ulcerative colitis (Clinical Activity Index [CAI] and Endoscopic Index [EI] according to Rachmilewitz, CAI 6-12; EI >/=4). Three different doses of 5-aminosalicylic acid (0.5 g 3 times a day, 1.0 g 3 times a day, and 1.5 g 3 times a day) were studied for 8 weeks.
  
  
  RESULTS
  Clinical remission rate (CAI </=4) was highest in the 1.0 g 3 times a day group (66 %), 50% in the 0.5 g 3 times a day group, and 55% in the 1.5 g 3 times a day group. Hierarchical testing showed no significance, indicating a lack of dose response across the 3 mesalamine doses. In addition, times to first clinical response were similar: 26.5 days (1.0 g 3 times a day), 27.5 days (0.5 g 3 times a day), and 21.5 days (1.5 g 3 times a day). Endoscopic improvement was better with 1.0 g mesalamine 3 times a day than with 0.5 g 3 times a day, but overall endoscopic and histologic improvement was not different between treatment groups. Baseline activity, duration, and localization of ulcerative colitis did have some influence on the therapeutic activity, but there was no significant interaction with the dose of the study drug. Safety, with special focus on kidney function, was excellent in all 3 groups.
  
  
  CONCLUSIONS
  There is no significant dose response between mesalamine 1.5 g/day, 3.0 g/day, and 4.5 g/day. The optimal dose to induce remission of ulcerative colitis is 0.5 g 5-aminosalicylic acid 3 times a day. Patients failing with this dose may benefit from an increase of the dose up to 1.0 g 3 times a day, but should also be considered for alternative treatment. A newly developed pellet formulation of 5-aminosalicylic acid has promising efficacy and excellent safety.
authors.affiliation: Evangelisches Krankenhaus Kalk, University of Cologne, Cologne, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kruis
authors.forename: Simon
authors.initials: S
authors.lastname: Bar-Meir
authors.forename: Janos
authors.initials: J
authors.lastname: Feher
authors.forename: Oliver
authors.initials: O
authors.lastname: Mickisch
authors.forename: Horst
authors.initials: H
authors.lastname: Mlitz
authors.forename: Marek
authors.initials: M
authors.lastname: Faszczyk
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Chowers
authors.forename: Gabriella
authors.initials: G
authors.lastname: Lengyele
authors.forename: Agotá
authors.initials: A
authors.lastname: Kovacs
authors.forename: László
authors.initials: L
authors.lastname: Lakatos
authors.forename: Manfred
authors.initials: M
authors.lastname: Stolte
authors.forename: Michael
authors.initials: M
authors.lastname: Vieth
authors.forename: Roland
authors.initials: R
authors.lastname: Greinwald
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D019804:Mesalamine / Q000008:administration & dosage*; D008875:Middle Aged; D011788:Quality of Life; D012074:Remission Induction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019804:Mesalamine