The response to 5-aminosalicylic acid (5-ASA) in mild and moderately active Crohn's disease localized in the small bowel was studied in a randomized, double-blind, placebo-controlled trial in four centres. Sixty-seven patients were included, of whom 30 were treated with 1500 mg slow-release 5-ASA/day (Pentasa) for a scheduled period of 16 weeks. In the 5-ASA group 40% of the patients improved, versus 30% of the placebo-treated group ('intent to treat' basis; p greater than 0.1). Four of the patients treated with 5-ASA left the study owing to disease deterioration, versus 10 of the placebo-treated patients (p greater than 0.2). Seventeen patients were secondarily excluded, and the remaining 50 patients (23 receiving 5-ASA) were reevaluated in greater detail. No statistically significant differences in outcome were shown. Three patients (one given 5-ASA) were withdrawn from the study because of presumed side effects, but no serious adverse reactions were recorded. The present results indicate that 5-ASA, at least in the dosage used, is not superior to placebo. Nevertheless, trends towards a beneficial effect in Crohn's disease in the small bowel justify further clinical trials with a larger dosage of 5-ASA.
Risk measured from this design can be shown to correlate strongly with the rate difference, a measure that is more clinically relevant than conventional relative risk estimates. Strong risk factors for NSAID-related ulcer complication are high age, male sex, ulcer history, and dyspepsia related to the NSAID therapy. Avoiding NSAID therapy in these high-risk patients, whenever possible, might prevent many adverse events.
SUMMARYThe role of arachidonic acid metabolites and the mode of action of 5-aminosalicylic acid, the active moiety of sulphasalazine and disodium azodisalicylate, in ulcerative colitis remain obscure. Therefore, experiments were performed in which the effects of medication on immunoreactive prostaglandin (PG) E2 concentrations in free faecal water were assessed using the equilibrium in vivo dialysis of faeces. Colonic PGE2 concentrations in patients with active ulcerative colitis (n= 11) ranged from 2035-18 000 pg/ml to be compared with a range of 103-188 pg/ml in healthy volunteers (n=10; p<0.001). In all healthy volunteers PGE2 concentrations decreased slightly (p<005) after disodium azodisalicylate intake 2 g/day, whereas low dose disodium azodisalicylate (0.25 g/day) caused no change. In patients with ulcerative colitis in complete clinical, sigmoidoscopic, and histologic remission withdrawal of sulphasalazine (2 g/day; n=6) increased PGE2 concentrations to values above normal levels (p<005) which returned to pretrial values (p<005) on disodium azodisalicylate (2 g/day; n=7). In conclusion, increased PGE2 in free faecal water indicates an abnormality in the colonic mucosa, even in the absence of conventional signs of inflammation. We could not confirm the hypothesis that sulphasalazine and 5-aminosalicylic acid exert their therapeutic effect through promotion of endogenous cytoprotective prostaglandins. In contrast, the observation that raised PGE2 concentrations were normalised by disodium azodisalicylate in patients with inactive ulcerative colitis suggests that subclinical disease activity was decreased by 5-aminosalicylic acid.Both cyclooxygenase and lipoxygenase products of arachidonic acid metabolism have been implicated in the pathogenesis of ulcerative colitis. The findings of increased amounts of prostanoids in faeces and rectal mucosa of patients with ulcerative colitisl-3 provided the hypothesis that prostaglandins may mediate the inflammatory response. The therapeutic effect of 5-aminosalicylic acid which is proved to be the major, though not necessarily the only active component of sulphasalazine,4 may be related to the anti-inflammatory activity of the substance which is a salicylate and a weak prostaglandin
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.