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What dose of 5-aminosalicylic acid (mesalazine) in ulcerative colitis?
  1. S A RILEY
  1. Department of Gastroenterology,
  2. Northern General Hospital,
  3. Sheffield S5 7AU, UK

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Sulphasalazine was developed in the 1930s, initially for use in patients with rheumatic polyarthritis. However, its modest effects in arthritis were soon overshadowed by the striking benefits seen when the drug was given to patients with active colitis.1Controlled clinical trials confirmed the early favourable impressions and established a role for sulphasalazine in the treatment of active disease and in the maintenance of disease remission.2-5Long term benefit was shown and lifelong treatment is usually recommended.6

Although sulphasalazine has had undoubted benefits for many patients with ulcerative colitis, it has two major limitations. Firstly, it has limited efficacy. In active disease, little more than half the patients treated with oral sulphasalazine will achieve symptomatic remission and, even with optimal maintenance treatment, annual relapse rates may be 30% or more. Secondly, side effects and allergic reactions are common, occurring in up to one third of patients taking standard maintenance doses and up to half of those taking therapeutic doses.7 Although many of these reactions are minor, some are serious and in about 10% they are sufficient to require discontinuation of treatment.

In 1977, Azad Khan et al studied the therapeutic activity of the component parts of sulphasalazine and found that 5-aminosalicylic acid (5-ASA; mesalazine) was the active ingredient and that sulphapyridine was therapeutically inert.8 As most of the adverse reactions to sulphasalazine were thought to be caused by sulphapyridine, the results of this landmark study suggested that new formulations should be developed to deliver 5-ASA to the colon without the toxic sulphapyridine carrier. Such drugs were to offer two potential advantages over conventional sulphasalazine. Firstly, they would be less toxic, better tolerated agents for either first-line use or for the treatment of patients intolerant of sulphasalazine. Secondly, reduced toxicity would permit the use of higher doses …

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