, Volume 63, Supplement 2, pp 21–33

Long-Acting β2-Agonists or Leukotriene Receptor Antagonists as Add-On Therapy to Inhaled Corticosteroids for the Treatment of Persistent Asthma

Review Article


It is well accepted that the combination of inhaled corticosteroids (ICSs) and long-acting β2-agonists (LABAs) is effective in achieving asthma control, as it treats both components of asthma pathophysiology, namely inflammation and smooth muscle dysfunction of the airways. Leukotriene receptor antagonists (LTRAs) can also be used as add-ons to ICS therapy in patients whose asthma is not controlled by ICSs alone. The purpose of this review is to compare the effectiveness of ICSs plus LABAs with that of ICSs plus LTRAs for the treatment of persistent asthma that is not controlled by ICSs alone.

Several studies have shown that, in comparison with an ICS plus an LTRA, the addition of an LABA to ICS therapy provides greater improvements in pulmonary function and overall control of asthma as measured by use of rescue medication and the number of exacerbations of the asthma, symptom-free days and symptom-free nights. The greater improvements in pulmonary function observed with an ICS plus the LABA, salmeterol, occurred within the first week of treatment (at first treatment assessment), and remained significantly greater than those achieved with an ICS plus an LTRA over the duration of the treatment. Moreover, the salmeterol-fluticasone propionate combination (SFC) produces consistently greater improvements in pulmonary lung function and control of asthma than does the addition of an LTRA to fluticasone propionate. In addition, SFC is a more cost-effective treatment option than fluticasone propionate plus montelukast for patients with asthma that is uncontrolled by ICSs alone. Important cost savings can be made with SFC in clinical practice compared with other combinations of ICSs plus salmeterol or ICSs plus LTRAs.


  1. 1.
    Bousquet J, Jeffery PK, Busse WW, et al. Asthma. From bronchoconstriction to airways inflammation and remodeling. Am J Respir Crit Care Med 2000; 161: 1720–45PubMedGoogle Scholar
  2. 2.
    British Thoracic Society. The British Guidelines on Asthma Management: 1995 review and position statement. Thorax 1997; 52 Suppl. 1: 1–21CrossRefGoogle Scholar
  3. 3.
    Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. Bethesda (MD): National Institutes of Health, National Heart, Lung, and Blood Institute; 2002. NIH Publication No. 02-3659Google Scholar
  4. 4.
    National Asthma Education and Prevention Program. Expert Panel Report 2. Guidelines for the Diagnosis and Management of Asthma. Bethesda (MD): National Institutes of Health, National Heart, Lung, and Blood Institute; 1997. NIH Publication No. 97-4051Google Scholar
  5. 5.
    Pauwels RA, Lofdahl CG, Postma DS, et al. Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group. N Engl J Med 1997; 337: 1405–11Google Scholar
  6. 6.
    Greening AP, Ind PW, Northfield M, et al. Added salmeterol versus higher-dose corticosteroid in asthma patients with symptoms on existing inhaled corticosteroid. Allen & Hanburys Limited UK Study Group. Lancet 1994; 344: 219–24PubMedCrossRefGoogle Scholar
  7. 7.
    Woolcock A, Lundback B, Ringdal N, et al. Comparison of addition of salmeterol to inhaled steroids with doubling of the dose of inhaled steroids. Am J Respir Crit Care Med 1996; 153: 1481–8PubMedGoogle Scholar
  8. 8.
    Davies B, Brooks G, Devoy M. The efficacy and safety of salmeterol compared to theophylline: meta-analysis of nine controlled studies. Respir Med 1998; 92: 256–63PubMedCrossRefGoogle Scholar
  9. 9.
    Wilson AJ, Gibson PG, Coughlan J. Long acting beta-agonists versus theophylline for maintenance treatment of asthma. Cochrane Database Syst Rev 2000; (2): CD001281Google Scholar
  10. 10.
    Simons FE, Villa JR, Lee BW, et al. Montelukast added to budesonide in children with persistent asthma: a randomized, double-blind, crossover study. J Pediatr 2001; 138: 694–8PubMedCrossRefGoogle Scholar
  11. 11.
    Laviolette M, Malmstrom K, Lu S, et al. Montelukast added to inhaled beclomethasone in treatment of asthma. Montelukast/Beclomethasone Additivity Group. Am J Respir Crit Care Med 1999; 160: 1862–8PubMedGoogle Scholar
  12. 12.
    Christian Virchow J, Prasse A, Naya I, et al. Zafirlukast improves asthma control in patients receiving high-dose inhaled corticosteroids. Am J Respir Crit Care Med 2000; 162 (2 Pt 1): 578–85Google Scholar
  13. 13.
    Lofdahl CG, Reiss TF, Leff JA, et al. Randomised, placebo controlled trial of effect of a leukotriene receptor antagonist, montelukast, on tapering inhaled corticosteroids in asthmatic patients. BMJ 1999; 319: 87–90PubMedCrossRefGoogle Scholar
  14. 14.
    Robinson DS, Campbell D, Barnes PJ. Addition of leukotriene antagonists to therapy in chronic persistent asthma: a randomised double-blind placebo-controlled trial. Lancet 2001; 357: 2007–11PubMedCrossRefGoogle Scholar
  15. 15.
    Ducharme FM. Anti-leukotrienes as add-on therapy to inhaled glucocorticoids in patients with asthma: systematic review of current evidence. BMJ 2002; 324: 1545PubMedCrossRefGoogle Scholar
  16. 16.
    Fish JE, Israel E, Murray JJ, et al. Salmeterol powder provides significantly better benefit than montelukast in asthmatic patients receiving concomitant inhaled corticosteroid therapy. Chest 2001; 120: 423–30PubMedCrossRefGoogle Scholar
  17. 17.
    Nelson HS, Nathan RA, Kalberg C, et al. Comparison of inhaled salmeterol and oral zafirlukast in asthmatic patients using concomitant inhaled corticosteroids. MedGenMed 2001; 3: 3PubMedGoogle Scholar
  18. 18.
    Busse W, Nelson H, Wolfe J, et al. Comparison of inhaled salmeterol and oral zafirlukast in patients with asthma. J Allergy Clin Immunol 1999; 103: 1075–80PubMedCrossRefGoogle Scholar
  19. 19.
    American Thoracic Society. Lung function testing: selection of reference values and interpretative strategies. Am Rev Respir Dis 1991; 144: 1202–18CrossRefGoogle Scholar
  20. 20.
    Wilson AM, Dempsey OJ, Sims EJ, et al. Evaluation of salmeterol or montelukast as second-line therapy for asthma not controlled with inhaled corticosteroids. Chest 2001; 119: 1021–6PubMedCrossRefGoogle Scholar
  21. 21.
    Ringdal N, Eliraz A, Pruzinec P, et al. The salmeterol/ fluticasone combination is more effective than fluticasone plus oral montelukast in asthma. Respir Med 2003; 97: 234–41PubMedCrossRefGoogle Scholar
  22. 22.
    Nelson HS, Busse WW, Kerwin E, et al. Fluticasone propionate/salmeterol combination provides more effective asthma control than low-dose inhaled corticosteroid plus montelukast. J Allergy Clin Immunol 2000; 106: 1088–95PubMedCrossRefGoogle Scholar
  23. 23.
    Yurdakul AS, Calisir HC, Tunctan B, et al. Comparison of second controller medications in addition to inhaled corticosteroid in patients with moderate asthma. Respir Med 2002; 96: 322–9PubMedCrossRefGoogle Scholar
  24. 24.
    Pieters WR, Wilson KK, Smith HCE, et al. Cost-effectiveness of fluticasone propionate/salmeterol combination product and fluticasone propionate/montelukast in asthma [abstract]. Am J Respir Crit Care Med 2001; 163 (5 Pt 2): A643Google Scholar
  25. 25.
    Leibman AK, Stanford RH, Emmett A, et al. Cost-effectiveness of fluticasone propionate/salmeterol combination versus fluticasone + montelukast in the treatment of persistent asthma [poster C9]. The 98th International Conference of the American Thoracic Society; 2002 May 17–22; AtlantaGoogle Scholar
  26. 26.
    Booth PC, Capsey LJ, Langdon CG, et al. A comparison of the cost-effectiveness of alternative prophylactic therapies in the treatment of adult asthma. Br J Med Econ 1995; 8: 65–72Google Scholar
  27. 27.
    Santanello NC, Zhang J, Seidenberg B, et al. What are minimal important changes for asthma measures in a clinical trial? Eur Respir J 1999; 14: 23–7PubMedCrossRefGoogle Scholar
  28. 28.
    Stempel DA, O'Donnell JC, Meyer JW Inhaled corticosteroids plus salmeterol or montelukast: effects on resource utilization and costs. J Allergy Clin Immunol 2002; 109: 433–9PubMedCrossRefGoogle Scholar
  29. 29.
    O'Connor RD, O'Donnell JC, Pinto LA, et al. Two-year retrospective economic evaluation of three dual-controller therapies used in the treatment of asthma. Chest 2002; 121: 1028–35PubMedCrossRefGoogle Scholar
  30. 30.
    Ollendorf DA, Pozniak AS, Bowers BW, et al. Economic impact of salmeterol versus leukotriene modifiers in patients with chronic asthma. Chest 2000; 118: 185–6SGoogle Scholar
  31. 31.
    Gothard LR, O'Donnell JC, Johnson BA, et al. Cost consequences of dual controller therapy for asthma: inhaled corticosteroids used concurrently with either salmeterol or leukotriene modifiers. J Manag Care Pharm 2000; 6: 358–64Google Scholar

Copyright information

© Adis Data Information BV 2003

Authors and Affiliations

  1. 1.Molde Internal Medicine CentreMoldeNorway

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