Review article: high-dose aminosalicylates to induce and maintain remissions in ulcerative colitis.
Sulfasalazine was the first aminosalicylate to be used for induction and maintenance therapy of ulcerative colitis (UC). Initial trials demonstrated a dose response that was compromised by dose-related intolerance. Recognition that the 5-aminosalicylic acid moiety (5-ASA, mesalazine) is the active ingredient of sulfasalazine has allowed the development of sulpha-free formulations of mesalazine and alternative azo-bond derivatives (olsalazine, balsalazide) that substantially reduce the dose-related (and allergic) consequences of the sulfapyridine moiety of sulfasalazine. Dose-ranging studies of mesalazine formulations for induction of remission have demonstrated increased efficacy of oral mesalazine up to 4-4.8 g/day, particularly in patients with more moderate disease activity. Combination therapy with oral and rectal mesalazine provide additional efficacy for patients with both distal and extensive colitis. The mesalazine formulations have dose-related benefits without dose-related side effects. In contrast, the azo-bond formulations are compromised by secretory diarrhoea at doses providing greater than 2-2.4 g/day of mesalazine. There are less data regarding dose-related benefits of aminosalicylates to maintain remissions in UC greater than 1.6 g/day of mesalazine, although the absence of dose-related side effects allows continuation of the same inductive dose through maintenance treatment without dose-related toxicity.
Hanauer
S B
SB
Professor of Medicine and Clinical Pharmacology Chief, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago, 5841 S. Maryland Ave., MC 4076, Chicago, IL 60637, USA. shanauer@uchicago.edu
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D004334:Drug Administration Schedule; D006801:Humans; D019804:Mesalamine / Q000008:administration & dosage*; D012074:Remission Induction / Q000379:methods; D012460:Sulfasalazine / Q000008:administration & dosage*; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D012460:Sulfasalazine; D019804:Mesalamine