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Acute and chronic effects of a 5-lipoxygenase inhibitor in asthma: a 6-month randomized multicenter trial. Zileuton Study Group.
J Allergy Clin Immunol. 1996 Nov; 98(5 Pt 1):859-71.JA

Abstract

BACKGROUND

Leukotrienes produced by the 5-lipoxygenase pathway of arachidonic acid metabolism may mediate bronchoconstriction and inflammatory changes important in the pathophysiology of asthma. Leukotriene inhibition may be effective in asthma management.

OBJECTIVE

This clinical trial was performed to assess the long-term efficacy and safety of zileuton, an inhibitor of 5-lipoxygenase.

METHODS

In this multicenter, double-blind, parallel-group, placebo-controlled trial, 600 mg of zileuton, 400 mg of zileuton, or placebo was given orally, each four times daily for 6 months. Patients with mild to moderate asthma (n = 373), 18 to 62 years of age, being managed with regularly inhaled beta-agonist alone, were randomized to the zileuton or placebo groups (n = 122 to 126). Outcome measures included serial spirometry, daily peak expiratory flow rates, daytime and nocturnal symptoms, frequency of beta-agonist use, and number of asthma exacerbations treated with systemic corticosteroids.

RESULTS

An acute bronchodilatory effect was observed 2 to 5 hours after the initial dose of medication in both 400 mg zileuton and 600 mg zileuton groups compared to the placebo group. Both zileuton groups had significantly greater improvements in FEV1 than did the placebo group by day 8. On day 36, FEV1 improved 16% and 12% from baseline for patients treated with 600 mg zileuton and 400 mg zileuton, respectively, compared with an improvement of 6% for the placebo-treated group (p < 0.01, zileuton 600 mg vs placebo). Blood eosinophil levels were significantly reduced in both zileuton-treated groups compared with the placebo group. In the group receiving 600 mg zileuton, morning peak expiratory flow rate improved by 7% to 10%; daytime and nocturnal symptoms decreased by 37% and 31%, respectively; beta-agonist use decreased by 31%; and the proportion of patients requiring steroid rescue medication during the study was reduced by 62% (p < 0.05 for all comparisons of zileuton, 600 mg, vs placebo). Improvements were sustained over 6 months. Adverse events were similar in the three groups with no apparent, dose-related side effects.

CONCLUSION

Zileuton produces objective and subjective improvements in patients with mild to moderate asthma and is well tolerated.

Authors+Show Affiliations

Department of Medicine, Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224-6801, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8939149

Citation

Liu, M C., et al. "Acute and Chronic Effects of a 5-lipoxygenase Inhibitor in Asthma: a 6-month Randomized Multicenter Trial. Zileuton Study Group." The Journal of Allergy and Clinical Immunology, vol. 98, no. 5 Pt 1, 1996, pp. 859-71.
Liu MC, Dubé LM, Lancaster J. Acute and chronic effects of a 5-lipoxygenase inhibitor in asthma: a 6-month randomized multicenter trial. Zileuton Study Group. J Allergy Clin Immunol. 1996;98(5 Pt 1):859-71.
Liu, M. C., Dubé, L. M., & Lancaster, J. (1996). Acute and chronic effects of a 5-lipoxygenase inhibitor in asthma: a 6-month randomized multicenter trial. Zileuton Study Group. The Journal of Allergy and Clinical Immunology, 98(5 Pt 1), 859-71.
Liu MC, Dubé LM, Lancaster J. Acute and Chronic Effects of a 5-lipoxygenase Inhibitor in Asthma: a 6-month Randomized Multicenter Trial. Zileuton Study Group. J Allergy Clin Immunol. 1996;98(5 Pt 1):859-71. PubMed PMID: 8939149.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Acute and chronic effects of a 5-lipoxygenase inhibitor in asthma: a 6-month randomized multicenter trial. Zileuton Study Group. AU - Liu,M C, AU - Dubé,L M, AU - Lancaster,J, PY - 1996/11/1/pubmed PY - 1996/11/1/medline PY - 1996/11/1/entrez SP - 859 EP - 71 JF - The Journal of allergy and clinical immunology JO - J. Allergy Clin. Immunol. VL - 98 IS - 5 Pt 1 N2 - BACKGROUND: Leukotrienes produced by the 5-lipoxygenase pathway of arachidonic acid metabolism may mediate bronchoconstriction and inflammatory changes important in the pathophysiology of asthma. Leukotriene inhibition may be effective in asthma management. OBJECTIVE: This clinical trial was performed to assess the long-term efficacy and safety of zileuton, an inhibitor of 5-lipoxygenase. METHODS: In this multicenter, double-blind, parallel-group, placebo-controlled trial, 600 mg of zileuton, 400 mg of zileuton, or placebo was given orally, each four times daily for 6 months. Patients with mild to moderate asthma (n = 373), 18 to 62 years of age, being managed with regularly inhaled beta-agonist alone, were randomized to the zileuton or placebo groups (n = 122 to 126). Outcome measures included serial spirometry, daily peak expiratory flow rates, daytime and nocturnal symptoms, frequency of beta-agonist use, and number of asthma exacerbations treated with systemic corticosteroids. RESULTS: An acute bronchodilatory effect was observed 2 to 5 hours after the initial dose of medication in both 400 mg zileuton and 600 mg zileuton groups compared to the placebo group. Both zileuton groups had significantly greater improvements in FEV1 than did the placebo group by day 8. On day 36, FEV1 improved 16% and 12% from baseline for patients treated with 600 mg zileuton and 400 mg zileuton, respectively, compared with an improvement of 6% for the placebo-treated group (p < 0.01, zileuton 600 mg vs placebo). Blood eosinophil levels were significantly reduced in both zileuton-treated groups compared with the placebo group. In the group receiving 600 mg zileuton, morning peak expiratory flow rate improved by 7% to 10%; daytime and nocturnal symptoms decreased by 37% and 31%, respectively; beta-agonist use decreased by 31%; and the proportion of patients requiring steroid rescue medication during the study was reduced by 62% (p < 0.05 for all comparisons of zileuton, 600 mg, vs placebo). Improvements were sustained over 6 months. Adverse events were similar in the three groups with no apparent, dose-related side effects. CONCLUSION: Zileuton produces objective and subjective improvements in patients with mild to moderate asthma and is well tolerated. SN - 0091-6749 UR - https://www.unboundmedicine.com/medline/citation/8939149/Acute_and_chronic_effects_of_a_5_lipoxygenase_inhibitor_in_asthma:_a_6_month_randomized_multicenter_trial__Zileuton_Study_Group_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091674996003077 DB - PRIME DP - Unbound Medicine ER -