Skip to main content
PMC home page
Thorax logoLink to Thorax
. 2000 Jun;55(6):478–483. doi: 10.1136/thorax.55.6.478

Effect of leukotriene receptor antagonist therapy on the risk of asthma exacerbations in patients with mild to moderate asthma: an integrated analysis of zafirlukast trials

N Barnes 1, C Miller 1
PMCID: PMC1745774  PMID: 10817796

Abstract

BACKGROUND—Asthma exacerbations contribute substantially to morbidity, and their reduction is an important therapeutic objective. In this integrated analysis the risk of asthma exacerbations was assessed during treatment with the leukotriene receptor antagonist zafirlukast.
METHODS—Data were collected from all five double blind, multicentre, randomised, placebo controlled, 13 week trials of zafirlukast 20 mg twice daily performed in steroid-naive patients with mild to moderate asthma. Exacerbation data were collected prospectively during monitoring of adverse events and concomitant medication use. Pooled data were used to assess the relative risk of asthma exacerbations using three definitions: worsening of asthma leading to withdrawal from the study; requirement for additional anti-asthma therapy (excluding increased short acting β2 agonist use); and requirement for oral corticosteroid therapy.
RESULTS—The proportion of patients with an asthma exacerbation leading to withdrawal was consistently lower in the group treated with zafirlukast 20 mg twice daily than in the placebo group. Overall, the risk of an asthma exacerbation requiring withdrawal from zafirlukast therapy was approximately half that of placebo (odds ratio 0.45; 95% CI 0.26 to 0.76; p = 0.003). Similar results were observed for exacerbations requiring additional control medication (odds ratio = 0.47; 95% CI 0.30 to 0.74; p = 0.001) and oral corticosteroid rescue (odds ratio = 0.53; 95% CI 0.32 to 0.86; p = 0.010).
CONCLUSIONS—Zafirlukast in a dose of 20 mg twice daily reduces the risk of asthma exacerbations and the need for additional anti-asthma therapies, fulfilling an important goal of control medication in patients with mild to moderate asthma.



Full Text

The Full Text of this article is available as a PDF (161.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Busse W., Nelson H., Wolfe J., Kalberg C., Yancey S. W., Rickard K. A. Comparison of inhaled salmeterol and oral zafirlukast in patients with asthma. J Allergy Clin Immunol. 1999 Jun;103(6):1075–1080. doi: 10.1016/s0091-6749(99)70182-x. [DOI] [PubMed] [Google Scholar]
  2. Chervinsky P., van As A., Bronsky E. A., Dockhorn R., Noonan M., LaForce C., Pleskow W. Fluticasone propionate aerosol for the treatment of adults with mild to moderate asthma. The Fluticasone Propionate Asthma Study Group. J Allergy Clin Immunol. 1994 Oct;94(4):676–683. doi: 10.1016/0091-6749(94)90174-0. [DOI] [PubMed] [Google Scholar]
  3. Drazen J. M., O'Brien J., Sparrow D., Weiss S. T., Martins M. A., Israel E., Fanta C. H. Recovery of leukotriene E4 from the urine of patients with airway obstruction. Am Rev Respir Dis. 1992 Jul;146(1):104–108. doi: 10.1164/ajrccm/146.1.104. [DOI] [PubMed] [Google Scholar]
  4. Fabbri L., Burge P. S., Croonenborgh L., Warlies F., Weeke B., Ciaccia A., Parker C. Comparison of fluticasone propionate with beclomethasone dipropionate in moderate to severe asthma treated for one year. International Study Group. Thorax. 1993 Aug;48(8):817–823. doi: 10.1136/thx.48.8.817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Finnerty J. P., Wood-Baker R., Thomson H., Holgate S. T. Role of leukotrienes in exercise-induced asthma. Inhibitory effect of ICI 204219, a potent leukotriene D4 receptor antagonist. Am Rev Respir Dis. 1992 Apr;145(4 Pt 1):746–749. doi: 10.1164/ajrccm/145.4_Pt_1.746. [DOI] [PubMed] [Google Scholar]
  6. Fish J. E., Kemp J. P., Lockey R. F., Glass M., Hanby L. A., Bonuccelli C. M. Zafirlukast for symptomatic mild-to-moderate asthma: a 13-week multicenter study. The Zafirlukast Trialists Group. Clin Ther. 1997 Jul-Aug;19(4):675–690. doi: 10.1016/s0149-2918(97)80092-6. [DOI] [PubMed] [Google Scholar]
  7. Haahtela T., Järvinen M., Kava T., Kiviranta K., Koskinen S., Lehtonen K., Nikander K., Persson T., Reinikainen K., Selroos O. Comparison of a beta 2-agonist, terbutaline, with an inhaled corticosteroid, budesonide, in newly detected asthma. N Engl J Med. 1991 Aug 8;325(6):388–392. doi: 10.1056/NEJM199108083250603. [DOI] [PubMed] [Google Scholar]
  8. Israel E., Cohn J., Dubé L., Drazen J. M. Effect of treatment with zileuton, a 5-lipoxygenase inhibitor, in patients with asthma. A randomized controlled trial. Zileuton Clinical Trial Group. JAMA. 1996 Mar 27;275(12):931–936. [PubMed] [Google Scholar]
  9. Kerrebijn K. F., van Essen-Zandvliet E. E., Neijens H. J. Effect of long-term treatment with inhaled corticosteroids and beta-agonists on the bronchial responsiveness in children with asthma. J Allergy Clin Immunol. 1987 Apr;79(4):653–659. doi: 10.1016/s0091-6749(87)80163-x. [DOI] [PubMed] [Google Scholar]
  10. Liu M. C., Dubé L. M., 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 Nov;98(5 Pt 1):859–871. doi: 10.1016/s0091-6749(96)80002-9. [DOI] [PubMed] [Google Scholar]
  11. Malmstrom K., Rodriguez-Gomez G., Guerra J., Villaran C., Piñeiro A., Wei L. X., Seidenberg B. C., Reiss T. F. Oral montelukast, inhaled beclomethasone, and placebo for chronic asthma. A randomized, controlled trial. Montelukast/Beclomethasone Study Group. Ann Intern Med. 1999 Mar 16;130(6):487–495. doi: 10.7326/0003-4819-130-6-199903160-00005. [DOI] [PubMed] [Google Scholar]
  12. Nathan R. A., Bernstein J. A., Bielory L., Bonuccelli C. M., Calhoun W. J., Galant S. P., Hanby L. A., Kemp J. P., Kylstra J. W., Nayak A. S. Zafirlukast improves asthma symptoms and quality of life in patients with moderate reversible airflow obstruction. J Allergy Clin Immunol. 1998 Dec;102(6 Pt 1):935–942. doi: 10.1016/s0091-6749(98)70331-8. [DOI] [PubMed] [Google Scholar]
  13. Nathan R. A., Minkwitz M. C., Bonuccelli C. M. Two first-line therapies in the treatment of mild asthma: use of peak flow variability as a predictor of effectiveness. Ann Allergy Asthma Immunol. 1999 May;82(5):497–503. doi: 10.1016/S1081-1206(10)62728-7. [DOI] [PubMed] [Google Scholar]
  14. Noonan M. J., Chervinsky P., Brandon M., Zhang J., Kundu S., McBurney J., Reiss T. F. Montelukast, a potent leukotriene receptor antagonist, causes dose-related improvements in chronic asthma. Montelukast Asthma Study Group. Eur Respir J. 1998 Jun;11(6):1232–1239. doi: 10.1183/09031936.98.11061232. [DOI] [PubMed] [Google Scholar]
  15. Pauwels R. A., Löfdahl C. G., Postma D. S., Tattersfield A. E., O'Byrne P., Barnes P. J., Ullman A. Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group. N Engl J Med. 1997 Nov 13;337(20):1405–1411. doi: 10.1056/NEJM199711133372001. [DOI] [PubMed] [Google Scholar]
  16. Reiss T. F., Chervinsky P., Dockhorn R. J., Shingo S., Seidenberg B., Edwards T. B. Montelukast, a once-daily leukotriene receptor antagonist, in the treatment of chronic asthma: a multicenter, randomized, double-blind trial. Montelukast Clinical Research Study Group. Arch Intern Med. 1998 Jun 8;158(11):1213–1220. doi: 10.1001/archinte.158.11.1213. [DOI] [PubMed] [Google Scholar]
  17. Spector S. L., Smith L. J., Glass M. Effects of 6 weeks of therapy with oral doses of ICI 204,219, a leukotriene D4 receptor antagonist, in subjects with bronchial asthma. ACCOLATE Asthma Trialists Group. Am J Respir Crit Care Med. 1994 Sep;150(3):618–623. doi: 10.1164/ajrccm.150.3.8087328. [DOI] [PubMed] [Google Scholar]
  18. Taylor I. K., O'Shaughnessy K. M., Fuller R. W., Dollery C. T. Effect of cysteinyl-leukotriene receptor antagonist ICI 204.219 on allergen-induced bronchoconstriction and airway hyperreactivity in atopic subjects. Lancet. 1991 Mar 23;337(8743):690–694. doi: 10.1016/0140-6736(91)90277-v. [DOI] [PubMed] [Google Scholar]
  19. Weiss K. B., Gergen P. J., Hodgson T. A. An economic evaluation of asthma in the United States. N Engl J Med. 1992 Mar 26;326(13):862–866. doi: 10.1056/NEJM199203263261304. [DOI] [PubMed] [Google Scholar]
  20. Wilding P., Clark M., Thompson Coon J., Lewis S., Rushton L., Bennett J., Oborne J., Cooper S., Tattersfield A. E. Effect of long-term treatment with salmeterol on asthma control: a double blind, randomised crossover study. BMJ. 1997 May 17;314(7092):1441–1446. doi: 10.1136/bmj.314.7092.1441. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES