Selective 5-lipoxygenase inhibition by zileuton in the treatment of relapsing ulcerative colitis

Abstract

Objective To test the efficacy and safety of zileuton 800 mg twice daily for up to 4 weeks against placebo. Design and setting A randomized double-blind, placebo-controlled multicentre trial including 76 outpatients with relapsing mild to moderately active ulcerative colitis from seven specialist gastroenterological departments in three countries. Main outcome measures 'Clinical responsé as defined by the dichotomous end points, CR25 and CR10, to combine improvement in both symptom and endoscopy scores [50% or more decrease in stool character and rectal bleeding scores, stable or improved scores of abdominal/rectal pain or urgency, and a 25% (CR25) or 10% (CR10) decrease in total sigmoidoscopy score] and leukotriene B4 concentrations in rectal dialysis fluid. Results Forty patients were randomized to zileuton and 36 to placebo; 45 patients received concurrent sulphasalazine, while 31 received no such medication. A clinical response occurred more often in the zileuton group and significantly so (P <0.05) in patients without concurrent sulphasalazine. No adverse events or toxicity indicating an unfavourable affect on risk ratio were observed. The leukotriene B4 concentrations in rectal dialysis fluid were significantly inhibited by zileuton with a median inhibition of 72%. Conclusion More potent 5-lipoxygenase inhibition may reduce leukotriene B4 production further and improve clinical outcome. Hence, further studies of zileuton at higher doses and over a longer period of time seem worthwhile.