A trial of zileuton versus mesalazine or placebo in the maintenance of remission of ulcerative colitis

Background & Aims: Leukotriene B-4 is a major neutrophil chemoattractant detected during relapse of inflammatory bowel disease and represents a potentional therapeutic target. The aim of this study was to compare the efficacy of zileuton, an active 5-lipoxygenase inhibitor, with mesalazine and placebo in the maintenance of remission in ulcerative colitis. Methods: A double-blind, parallel-group, multicenter, and multinational trial was conducted during a Q-month period in hospital-based patients with inflammatory bowel disease. Three hundred five evaluable patients with ulcerative colitis in remission at the start of the trial were randomized into groups to undergo oral treatment with zileuton (600 mg old; n = 113), mesalazine (400 mg old; n = 99), or placebo (n = 111). The primary efficacy outcome was maintenance of remission for 6 months. A multivariate analysis was used to investigate determinants of relapse. Safety was assessed by treatment discontinuation, adverse events, vital signs, and laboratory parameters. Results: After 6 months, 54% of patients receiving zileuton remained in remission compared with 43% receiving placebo (P = 0.094) and 63% on mesalazine (P = 0.266). Relapse rates on mesalazine were significantly lower than those for placebo (P = 0.017). All treatments were well tolerated. Conclusions: Zileuton (600 mg old) was not significantly better than placebo in the maintenance of remission of ulcerative colitis in this trial and may have limited potential in the treatment of this condition.