Gastroenterology

Gastroenterology

Volume 112, Issue 3, March 1997, Pages 718-724
Gastroenterology

A trial of zileuton versus mesalazine or placebo in the maintenance of remission of ulcerative colitis. The European Zileuton Study Group For Ulcerative Colitis

https://doi.org/10.1053/gast.1997.v112.pm9041232Get rights and content

Abstract

BACKGROUND & AIMS: Leukotriene B4 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 6-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 qid; n = 113), mesalazine (400 mg qid; 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 qid) 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.

(Gastroenterology 1997 Mar;112(3):718-24)

References (0)

Cited by (117)

  • AGA Technical Review on the Management of Mild-to-Moderate Ulcerative Colitis

    2019, Gastroenterology
    Citation Excerpt :

    We identified 11 trials comparing different doses of mesalamine with each other or placebo for maintenance of remission, all of which enrolled patients in clinical and endoscopic remission, with or without histologic remission, for varying time periods of 6–12 months; outcome was reported as combined clinical and endoscopic remission based on validated disease activity indices. Standard-dose (2 RCTs, 510 patients; RR of failure to achieve remission, 0.55; 95% CI, 0.43–0.70)55,56 and low-dose (3 RCTs, 579 patients; RR, 0.63; 95% CI, 0.51–0.79)57–59 mesalamine were superior to placebo in maintaining remission in patients with mild–moderate UC (Supplementary Figure 4). With estimated placebo rates of maintenance of remission of 58%, 76.9%, and 73.5% patients treated with standard- and low-dose mesalamine maintained remission, respectively.

  • Comparative efficacy and tolerability of pharmacological agents for management of mild to moderate ulcerative colitis: a systematic review and network meta-analyses

    2018, The Lancet Gastroenterology and Hepatology
    Citation Excerpt :

    One trial covered intervention for both induction and maintenance of remission, and was thus considered in both groups. We therefore included 48 randomised trials (8020 participants, including 1380 placebo-treated patients) comparing eight active interventions for induction of remission,23–70 and 28 randomised trials (4218 participants, including 575 placebo-treated patients) comparing six active interventions for maintenance of remission.23,71–97 The available direct comparisons and network of trials for induction and maintenance of clinical remission are shown in figure 2.

  • Use of a balanced dual cyclooxygenase-1/2 and 5-lypoxygenase inhibitor in experimental colitis

    2016, European Journal of Pharmacology
    Citation Excerpt :

    Since the inhibition of one or both COX enzymes may shunt arachidonic acid metabolism to the 5-LOX pathway, zileuton, an active 5-lipoxygenase inhibitor, was compared in a trial versus mesalazine and placebo. However, zileuton was not superior to placebo in maintaining remission of symptoms in ulcerative colitis (Hawkey et al., 1997). Thus, it appears that a targeted inhibition of either COX or 5-LOX does not represent the proper therapeutic strategy to block the inflammatory response in IBDs.

View all citing articles on Scopus
View full text