Leukotrienes in ulcerative colitis: Results of a multicenter trial of a leukotriene biosynthesis inhibitor, MK-591

W. G. Roberts*, T. J. Simon, R. G. Berlin, R. C. Haggitt, E. S. Snyder, W. F. Stenson, S. B. Hanauer, J. E. Reagan, A. Cagliola, W. K. Tanaka, S. Simon, M. L. Berger

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

Background and Aims: Leukotrienes (LTs) are believed to be important in the pathogenesis of ulcerative colitis (UC). The aim of this study was to determine whether inhibition of LT biosynthesis with a 5-lipoxygenase inhibitor (MK-591) induces remission in patients with mild to moderate UC. Methods: One hundred eighty-three patients with mild to moderately active UC enrolled in this randomized parallel group, double-blind study. Patients received placebo or MK-591 at a dose of 12.5, 50, or 100 mg twice daily for 8 weeks. A subset of patients underwent rectal dialysis to determine LTB4 concentration. Results: MK-591 reduced LTB4 concentrations in rectal dialysate at the final determination. The median percent of baseline LTB4 concentration for 100 mg taken twice daily was 1.4% (n = 4); for 50 mg taken twice daily, 16.5% (n = 6); for 12.5 mg taken twice daily, 12% (n = 6); and for placebo, 78% (n = 6). There was no correlation between reduction of LTB4 and remission. Patients in remission at week 8 were as follows: placebo, 9 of 44 (20.5%); 100 mg taken twice daily, 11 of 43 (25.6%); 50 mg taken twice daily, 8 of 49 (16.3%); and 12.5 mg taken twice daily, 4 of 47 (8.5%) (P > 0.10). Conclusions: MK-591 markedly inhibited LT biosynthesis, but it did not differ significantly from placebo in clinical efficacy. Inhibition of LT biosynthesis was not effective as a single therapeutic modality in active UC.

Original languageEnglish (US)
Pages (from-to)725-732
Number of pages8
JournalGastroenterology
Volume112
Issue number3
DOIs
StatePublished - 1997

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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