A Double-Blind, Placebo Controlled, Multicentre Study of the Efficacy And Safety of 5-Aminosalicylic Acid Tablets in the Treatment of Ulcerative Colitis

This double-blind, placebo controlled, multicentre, parallel trialassessed the efficacy of two oral doses of a new formulation of 5-aminosalicylicacid (5-ASA) targeted to release in the cecum which was given for six weeks to136 patients with active ulcerative colitis. Seven centres participated (twoCanadian, five American). Patients were randomly assigned to one of threetreatment groups (4 g 5-ASA, 2 g 5-ASA or placebo). Medication wasdispensed as 250 mg identically appearing tablets containing either 5-ASA orplacebo to be taken four times a day. Subjects were assessed at baseline and afterthree and six weeks of treatment. Assessments included a disease activity index,physician's global assessment and flexible sigmoidoscopy. Compliance was assessedthrough pill count. A total of 136 patients participated ( 4 7 on 4 g 5-ASA,45 on 2 g 5-ASA, and 44 on placebo). The three groups were similar in terms ofage, weight, distribution of disease, extent of disease, and previous use of steroidsor sulphasalazine. Ninety patients completed the six week study. Of the 46dropouts, 38 (82.6%) left because of insufficient efficacy ( most on either place hoor 2 g 5-ASA), four (8.7%) had adverse reactions (all on 5-ASA), the remainingfour (8.7%) left for reasons not related to their ulcerative colitis. The diseaseactivity index represents a composite score ( maximum of 12) with categories fornumber of daily stools, presence of bleeding, abdominal pain and physician'sassessment of disease activity. Patients who received 4 g 5-ASA dailydemonstrated significant declines in disease activity index within three weeks oftherapy and maintained improvement until the end of the stuuy. Althoughdisease activity index declined for patients receiving 2 g 5-ASA daily, thesechanges did not reach statistical significance when compared to placebo-treatedpatients. On a five point scale (much improved, somewhat improved, unchanged,somewhat worse, much worse) the physician's global assessment mirrored thechanges in disease activity index. Patients randomized to receive 4 g 5-ASAtablets were consistently noted as being either much or somewhat improvedcompared to placebo-treated patients. Side effects were few and minor and52% (4 g 5-ASA), 42% (2 g 5-ASA) and 37% (placebo) of patients had nocomplaints. Headache was the most commonly cited adverse reaction for 6.9%(4 g 5-ASA) and 9.4% (2 g 5-ASA) of treated patients but 3.5% of placebo-treatedpatients also complained of headache. In conclusion in this randomizeddouble-blind, placebo controlled study, patients with active ulcerative colitisrandomized to 4 g 5-ASA per day noted improvement in disease activity asmeasured by disease activity index and physician's global assessment whencompared to placebo-treated patients. ln contrast, patients who received 2 g5-ASA daily did not demonstrate significant differences compared to theplacebo group