In a Danish multicentre trial we compared the relapse preventing effects of olsalazine and sulphasalazine in patients with ulcerative colitis over a 12 month treatment period. Two hundred and twenty seven patients (118 men) with at least two previous attacks of ulcerative colitis were randomly allocated according to a prearranged treatment schedule to olsalazine 500 mg bd or sulphasalazine 1 g bd in a double blind, double dummy fashion. One hundred and ninety seven patients completed the trial. The relapse rate after 12 month in the olsalazine group was 46.9% v 42.4% in the sulphasalazine group with a 95% confidence interval for the difference in proportions of -9% to 18%. Seven per cent of the patients were withdrawn from the trial because of adverse drug reactions and these were equally distributed between the two groups.

Frequent minor side effects are associated with sulfasalazine. The realization that it is the 5-aminosalicylic acid moiety that is the active component of sulfasalazine and that the side effects are probably due to the sulfapyridine has prompted the search for a similar but safer compound. Olsalazine, consisting of two molecules of 5-ASA without sulfasalazine may avoid the problems due to sulfasalazine. One hundred one patients were entered into a double-blind placebo-controlled study of the use of olsalazine (2 g daily) in preventing relapse in patients who had recently recovered from an acute attack of ulcerative colitis. Patients were treated for 12 months. Forty-nine were randomized to olsalazine (39 with limited and 10 with extensive disease) and 52 to placebo (42 with limited and 10 with extensive disease). Life-table analysis showed that the median time to relapse in patients on olsalazine was 342 days, which was significantly longer than the 100 days in the placebo group (P = 0.024). The most important side effect experienced with olsalazine that necessitated withdrawal from the study was "drug-induced diarrhea" in 16% (8/49). There was a similar incidence of minor side effects reported in the two groups, and in no patients were major or dangerous side effects reported. In patients who did not develop diarrhea, olsalazine was well tolerated and successfully prevented rapid relapse in the recently ill patients entered into this study.

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 (90% 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 of olsalazine for maintaining remission in ulcerative colitis is 1 g/day. For patients with proctitis or recent relapse, 2 g/day may be preferable, although the dose seems to be less important in patients with more extensive disease or those in long term remission.

Olsalazine is a compound consisting of two 5-amino salicylate (5-ASA) molecules linked by an azo bond, which, administered orally, is split by colonic bacteria to liberate 5-ASA. It lacks the sulfapyridine moiety found in sulfasalazine. Using a specific protocol, we conducted a randomized, double-blind, placebo-controlled trial of olsalazine in patients with symptomatic ulcerative colitis. Inclusion criteria included mild to moderate disease with involvement of more than 15 cm of colon, visible blood in stools, and the discontinuation of all other medications prior to and during the study. Patients were given oral olsalazine 3.0 g/day or placebo for 4 wk. Patients were evaluated clinically, by laboratory analysis and by colonoscopic evaluation, at entry and at 4 wk. Additional clinical and laboratory evaluations were performed at 2 wk. Fifteen patients entered the study. Of the seven patients randomized to olsalazine, four (57%) improved clinically and by colonoscopic scoring, one showed no improvement in either, and two (29%) withdrew after developing severe watery diarrhea. Of the eight patients treated with placebo, two (25%) improved clinically but were without colonscopic improvement and six (75%) worsened, of whom four withdrew early because of worsening symptoms of colitis. Seven of eight placebo patients were then treated with olsalazine on an open basis. Of these seven, five (71%) improved clinically and colonoscopically and two (29%) withdrew because of severe watery diarrhea. Overall, of 14 patients treated with Olsalazine, nine (64%) improved, one showed no improvement, and four (29%) discontinued because of persistent watery diarrhea. No other serious side effects were noted. Minor side effects included transient diarrhea, flares of acne, and anxiety attacks which resolved despite continuation of the drug.

Sulphasalazine extends remissions and lessens disease activity during relapses of ulcerative colitis, but it also causes many adverse side-effects. The adverse reactions are mostly attributable to the sulphapyridine carrier moiety rather than the active principle 5-aminosalicylic acid (5-ASA), so agents to deliver 5-ASA to the colon by other means have been designed. We have compared the efficacy and tolerability of two such agents, olsalazine and mesalazine, in maintenance therapy of ulcerative colitis. 100 patients with ulcerative colitis in remission were recruited at one centre and assigned randomly to treatment with olsalazine (Dipentum; 1.0 g daily) or mesalazine (Asacol, with Eudragit-S coating; 1.2 g daily). Compliance, biochemical and haematological variables, and clinical evidence of disease activity were assessed every 3 months for 12 months by observers unaware of treatment allocation. In intention-to-treat analysis, which included as treatment failures patients withdrawn for protocol violations, adverse reactions, intercurrent illness, or non-compliance as well as those with relapses of ulcerative colitis, the olsalazine group had a significantly lower rate of treatment failure than the mesalazine group (12/49 [24%] vs 23/50 [46%]; p = 0.025). Analysis restricted to 64 patients still in remission at 1 year and 18 with relapses also showed a significant difference in relapse rate (olsalazine 5/42 [12%] vs mesalazine 13/40 [33%]; p = 0.024). Both drugs were well tolerated; only 9 patients reported substantial side-effects. Olsalazine was clearly superior to mesalazine in prevention of relapses in ulcerative colitis, especially in patients with left-sided disease.

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OBJECTIVE: To compare the relapse-preventing effect and the frequency of adverse events of olsalazine and sulphasalazine in sulphasalazine-tolerant patients with ulcerative colitis. METHODS: Patients in remission, with at least two episodes of active disease during the last 5 yr, were randomized to 2 g of sulphasalazine or 1 g of olsalazine daily and were followed for 6-18 months. Relapse rates in the two groups were compared using frequency and life-table analysis. Sixty-nine patients with proctitis, 140 with left-sided colitis, and 113 with subtotal or total colitis were evaluated. RESULTS: In the intention-to-treat analysis, the failure rate (relapses plus withdrawals) was 54.7% in the olsalazine and 47.2% in the sulphasalazine group. In the per-protocol analysis excluding withdrawals, 44.7% relapsed in the olsalazine and 39.3% in the sulphasalazine group. Remission curves did not differ significantly, although at all time intervals the frequency of remission was slightly higher in the sulphasalazine group (p = 0.19 in the intention-to-treat analysis and p = 0.42 in the per-protocol analysis estimated by the log-rank test). Twelve patients (of whom five had diarrhea) in the olsalazine group versus eight patients in the sulphasalazine group discontinued the study because of side effects. CONCLUSION: The relapse-preventing effect of olsalazine and sulphasalazine in sulphasalazine-tolerant patients did not differ. Furthermore, the tolerability of olsalazine, particularly concerning diarrhea, appears to be better than previously reported.

Olsalazine (2 g/day) and sulphasalazine (3 g/day) were compared in a double blind three centre trial in 37 patients presenting with first attack of distal colitis. Sigmoidoscopic appearances, rectal biopsies, and symptom and stool diary records were used to assess benefit and adverse effects. Both groups showed a similar decrease in stool frequency (p less than 0.001). The proportion of unformed stools was also decreased, but to a lesser extent (p less than 0.05) in those taking olsalazine (78% v 55%; p less than 0.001) compared with those taking sulphasalazine (72% v 28%; p less than 0.001). There was a diminution in the proportion of stools containing blood in both groups (olsalazine: 61% v 22%; p less than 0.001/sulphasalazine: 67% v 37%; p less than 0.001). Sigmoidoscopic and histological appearances and clinical activity improved significantly and to a similar extent in both groups. Intolerance was encountered in two patients on olsalazine and four on sulphasalazine; intolerance to sulphasalazine being even higher (five of seven patients) in a preliminary study using a dose of sulphasalazine releasing the same amount of 5-aminosalicylic acid as 2 g olsalazine. Olsalazine was at least as effective as sulphasalazine in the treatment of new patients with distal colitis, and in a dose releasing an equivalent amount of 5-aminosalicylic acid was better tolerated.

Olsalazine, consisting of two salicylate radicals linked by an azo-bond, is effective in the treatment of active ulcerative colitis. To test its effect in patients with mild to moderate attacks of Crohn's disease, the International Organization for the Study of Inflammatory Bowel Disease (IOIBD) designed a multicentre, randomised, double-blind, placebo-controlled study. Ninety-one patients from four centres were randomised to receive either olsalazine, 1 g b.i.d., or matching placebo tablets. Twenty-six patients had ileal disease; 43, ileocolonic; and 22, colonic. Thirty-five of 46 patients taking olsalazine and 24 of 45 patients taking placebo were withdrawn before the end of the 4-month study. Diarrhoea was the most common reason for withdrawal from the olsalazine group, accounting for 22% of the patients, as compared with 4% in the placebo group. No other side effects were reported. There was no difference in the remission rate or withdrawal rate for active disease in the two groups. However, when an intent-to-treat analysis was performed, only eight of the 46 (17%) olsalazine-treated patients were considered to have entered remission or improved their symptoms compared with 22 of the 45 (49%) placebo-treated patients (p < 0.03). This study was unable to show that patients with mild to moderate attacks of Crohn's disease were significantly improved by treatment with olsalazine at a dose of 1 g daily. However, the potential benefit of a higher dose cannot be excluded.

Fifty-six patients with ulcerative colitis of mild to moderate severity were entered into a randomized, double-dummy comparison of sulphasalazine, 3 g/day, with olsalazine, 3 g/day. Patients were assessed clinically, and by sigmoidoscopy and biopsy, on entry and at 5 weeks. Both agents produced a similar reduction in stool frequency and in the passage of blood and mucus. Improvements in sigmoidoscopic and histological appearances of the rectal mucosa were observed to a similar extent in both groups of patients. Two patients treated with olsalazine were withdrawn because of increased diarrhoea attributable to the medication. Two patients given sulphasalazine for the first time developed a skin rash. Other side-effects seen during the trial were mild. In this small short-term study, oral olsalazine appeared to be as effective as sulphasalazine in the treatment of mild to moderate ulcerative colitis.