Optimum dose of olsalazine for maintaining remission in ulcerative colitis

To evaluate the optimum dose of olsalazine for maintaining remission in ulcerative colitis, 198 patients in remission for more than three months were randomly assigned to receive 0.5 g, 1.0 g, or 2.0 g/day for 12 months. A dose-ranging effect was detected in the per protocol analysis, with remission rates of 60% (0.5 g), 70% (1.0 g), and 78% (2.0 g) (p=0.03, trend in proportions). The higher dose was most effective in patients with proctitis (90Gb remission on 2 g/day, p=0.03) or those in remission for less than 12 months before the trial (88% remission on 2 g/day, p=0.0006). There was little dose-ranging effect in patients with extensive colitis or those in remission for more than 12 months. Diarrhoea necessitated treatment withdrawal in 12%. The optimal dose ofolsalazine for maintaining remission in ulcerative colitis is 1 g/day. For patients with proctitis or recent relapse, 2 g/day may be preferabJle, although the dose seems to be less important in patients with more extensive disease or those in long term remission. (Gut 1994; 35: 1282-1286) Gastroenterology Unit, Radcliffe Infirmary, Oxford S P L Travis H J de Silva D P Jewell Department of Medicine, Division of Gastroenterology, Orebro Medical Center Hospital, Orebro, Sweden C Tysk H Sandberg-Gertzen G Jarnerot Correspondence to: Dr D P Jewell, Gastroenterology Unit, Radcliffe Infirmary, Oxford OX2 6HE. Accepted for publication 14 December 1993 Olsalazine was developed as an alternative to sulphasalazine for the treatment of ulcerative colitis, in order to avoid the side effects of sulphasalazine attributable to the sulphapyridine moiety.' 2 The drug consists of two molecules of 5-aminosalicylic acid (5-ASA) joined by an azo bond that is split by bacterial azoreductase to release 5-ASA in the colon.3 Olsalazine is now well established in the treatment of ulcerative colitis. A dose of 1 g/day compared with placebo reduced the six month relapse rate from 45% to 23% in a randomised trial of 160 patients who were intolerant of sulphasalazine,4 and in another study of 162 patients, olsalazine 1 g/day was as effective as sulphasalazine 2 g/day for maintaining remission.5 This has since been confirmed.6 Olsalazine is well tolerated by over 80% of patients who are intolerant of sulphasalazine.4 For maintaining remission with sulphasalazine, Azad Khan et al 7 showed that greater therapeutic efficacy could be obtained by increasing the dose, although 2 g daily was optimal in terms of efficacy with the least side effects. However, whether there is a similar dose response effect for olsalazine when used for maintenance therapy is unknown. In a small study of 66 patients with active ulcerative colitis treated with olsalazine, a higher dose (3 g/day) was more effective than 1.5 g, 0.75 g, or placebo.8 Consequently, a dose-ranging study of olsalazine in the maintenance of remission in ulcerative colitis was designed. Particular attention was paid to the relationship between dose efficacy and the extent of disease and the safety profile of different doses, in view of reports that a small intestinal secretory diarrhoea may be induced by olsalazine.9