, Volume 28, Issue 7, pp 585–595 | Cite as

Cost Effectiveness of Leukotriene Receptor Antagonists versus Inhaled Corticosteroids for Initial Asthma Controller Therapy

A Pragmatic Trial
  • Edward C. F. WilsonEmail author
  • Erika J. Sims
  • Stanley D. Musgrave
  • Lee Shepstone
  • Annie Blyth
  • Jamie Murdoch
  • H. Miranda Mugford
  • Elizabeth F. Juniper
  • Jon G. Ayres
  • Stephanie Wolfe
  • Daryl Freeman
  • Richard F. T. Gilbert
  • Ian Harvey
  • Elizabeth V. Hillyer
  • David Price
Original Research Article Leukotriene Receptor Antagonists vs Inhaled Corticosteroids in Asthma


Background: Information is lacking on the relative effectiveness and cost effectiveness — in a primary-care setting — of leukotriene receptor antagonists (LTRAs) as an alternative to inhaled corticosteroids (ICS) for initial asthma controller therapy.

Objective: To compare the cost effectiveness of LTRAs versus ICS for patients initiating asthma controller therapy.

Methods: An economic evaluation was conducted alongside a 2-year, pragmatic, randomized controlled trial set in 53 primary-care practices in the UK. Patients aged 1280 years with asthma and symptoms requiring regular antiinflammatory therapy (n = 326) were randomly assigned to LTRAs (n = 162) or ICS (n = 164). The main outcome measures were the incremental costs per point improvement in the Mini Asthma Quality of Life Questionnaire, per point improvement in the Asthma Control Questionnaire and per QALY gained from the UK NHS and societal perspectives.

Results: Over 2 years, resource use was similar between the two treatment groups, but the cost to society per patient was significantly higher for the LTRA group, at £711 versus £433 for the ICS group (adjusted difference £204; 95% CI 74, 308) [year 2005 values]. Cost differences were driven primarily by differences in prescription drug costs, particularly study drug costs. There was a nonsignificant (imputed, adjusted) difference between treatment groups, favouring ICS, in QALYs gained at 2 years of −0.073 (95% CI −0.143, 0.010). Therapy with LTRAs was, on average, a dominated strategy, and, at a threshold for willingness to pay of £30 000 per QALY gained, the probability of LTRAs being cost effective compared with ICS was approximately 3% from both societal and NHS perspectives.

Conclusions: There is a very low probability of LTRAs being cost effective in the UK, at 2005 values, compared with ICS for initial asthma controller therapy.

Trial registration: UK National Research Register N0547145240; Controlled Clinical Trials ISRCTN99132811.


Asthma Fluticasone Propionate Montelukast Zafirlukast Supplemental Digital Content 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors thank all the patients and their families for their participation and support during the study. We gratefully acknowledge the support and assistance of many who have helped this study, including GPs, nurses and administrative staff in the participating practices; Julie Houghton, Emma Koro, Sasha Rust-Andrews and Carole Bull of the research team; Dr Alistair Lipp for advice on study design and delivery; Dr Mark L. Levy (Clinical Research Fellow: Allergy and Respiratory Research Group, Division of Community Health Sciences, University of Edinburgh, Scotland) for advice on the initial study design and implementation; Jon Bell for advice on peak flow measurement; and Linda Kemp of Respiratory Research Ltd for assistance with the analyses.

This project was funded by the Health Technology Assessment Programme (project number 98/34/05). The views and opinions expressed herein are those of the authors and do not necessarily reflect those of the Department of Health (UK). Additional support was provided for the implementation of the study from Clement-Clarke International and by unrestricted educational grants from Merck Sharpe and Dohme Ltd, AstraZeneca Ltd and Research in Real Life Ltd who contributed 9% of the total budget.

For a list of the contributions of the authors to the study and their conflicts of interest, see the Supplemental Digital Content 2,

Supplementary material

40273_2012_28070585_MOESM1_ESM.pdf (159 kb)
Supplementary material, approximately 163 KB.
40273_2012_28070585_MOESM2_ESM.pdf (82 kb)
Supplementary material, approximately 84 KB.


  1. 1.
    British Thoracic Society, Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma: a national clinical guideline. London: NHS Quality Improvement Scotland, 2008 May, updated 2009 Jun [online]. Available from URL: [Accessed 2010 Apr 23]Google Scholar
  2. 2.
    Global Initiative for Asthma. GINA report, global strategy for asthma management and prevention [online]. Available from URL: [Accessed 2010 Apr 23]
  3. 3.
    British National Formulary. 50th ed. London: British Medical Association and the Royal Pharmaceutical Society of Great Britain, 2005Google Scholar
  4. 4.
    Baumgartner RA, Martinez G, Edelman JM, et al. Distribution of therapeutic response in asthma control between oral montelukast and inhaled beclomethasone. Eur Respir J 2003; 21: 123–8PubMedCrossRefGoogle Scholar
  5. 5.
    Drazen JM, Silverman EK, Lee TH. Heterogeneity of therapeutic responses in asthma. Br Med Bull 2000; 56: 1054–70PubMedCrossRefGoogle Scholar
  6. 6.
    Jones C, Santanello NC, Boccuzzi SJ, et al. Adherence to prescribed treatment for asthma: evidence from pharmacy benefits data. J Asthma 2003; 40: 93–101PubMedCrossRefGoogle Scholar
  7. 7.
    Kelloway JS, Wyatt RA, Adlis SA. Comparison of patients’ compliance with prescribed oral and inhaled asthma medications. Arch Intern Med 1994; 154: 1349–52PubMedCrossRefGoogle Scholar
  8. 8.
    Lazarus SC, Chinchilli VM, Rollings NJ, et al. Smoking affects response to inhaled corticosteroids or leukotriene receptor antagonists in asthma. Am J Respir Crit Care Med 2007; 175: 783–90PubMedCrossRefGoogle Scholar
  9. 9.
    Herland K, Akselsen JP, Skjonsberg OH, et al. How representative are clinical study patients with asthma or COPD for a larger ‘real life’ population of patients with obstructive lung disease? Respir Med 2005; 99: 11–9PubMedCrossRefGoogle Scholar
  10. 10.
    Travers J, Marsh S, Williams M, et al. External validity of randomised controlled trials in asthma: to whom do the results of the trials apply? Thorax 2007; 62: 219–23PubMedCrossRefGoogle Scholar
  11. 11.
    Price D, Musgrave SD, Wilson E, et al. A pragmatic singleblind randomised controlled trial and economic evaluation of the use of leukotriene receptor antagonists in primary care at steps 2 and 3 of the national asthma guidelines. Health Technol Assess. In pressGoogle Scholar
  12. 12.
    NHS Connecting for Health. MIQUEST [online]. Available from URL: [Accessed 2010 Apr 28]
  13. 13.
    Apollo Medical Systems. SQL Suite [online]. Available from URL: [Accessed 2010 Apr 28]
  14. 14.
    Department of Health. NHS reference costs 2005 [online]. Available fromURL: [Accessed 2010 Apr 23]
  15. 15.
    Office for National Statistics. Annual Survey of Hours and Earnings (ASHE). 2005 [online]. Available from URL: [Accessed 2010 Apr 23]Google Scholar
  16. 16.
    Office for National Statistics. All items retail prices index (RPI): table RP02. London: Office for National Statistics [online]. Available from URL: [Accessed 2010 Apr 23]
  17. 17.
    HM Treasury. The green book: appraisal and evaluation in central government. London: HM Treasury: section 5.49 [online]. Available from URL: [Accessed 2010 Apr 23]
  18. 18.
    National Institute for Health and Clinical Excellence (NICE). Guide to the methods of technology appraisal. London: NICE, 2008 Jun: section 5.6 [online]. Available from URL: [Accessed 2010 Apr 23]Google Scholar
  19. 19.
    Juniper EF, Guyatt GH, Cox FM, et al. Development and validation of the Mini Asthma Quality of Life Questionnaire. Eur Respir J 1999; 14: 32–8PubMedCrossRefGoogle Scholar
  20. 20.
    Juniper EF, Svensson K, Mork AC, et al. Measurement properties and interpretation of three shortened versions of the Asthma Control Questionnaire. Respir Med 2005; 99: 553–8PubMedCrossRefGoogle Scholar
  21. 21.
    The EuroQol Group. EuroQol: a new facility for the measurement of health-related quality of life. Health Policy 1990; 16: 199–208CrossRefGoogle Scholar
  22. 22.
    Dolan P. Modeling valuations for EuroQol health states. Med Care 1997; 35: 1095–108PubMedCrossRefGoogle Scholar
  23. 23.
    Drummond MF, Sculpher MJ, Torrance GW, et al. Quality adjusted life years. In: Drummond MF, Sculpher MJ, Torrance GW, editors. Methods for the economic evaluation of health care programmes. 3rd ed. Oxford: Oxford University Press, 2005: 173–88Google Scholar
  24. 24.
    Rubin DB. Multiple imputation for nonresponse in surveys. Hoboken (NJ): John Wiley & Sons, 1987CrossRefGoogle Scholar
  25. 25.
    Fenwick E, Claxton K, Sculpher M. Representing uncertainty: the role of cost-effectiveness acceptability curves. Health Econ 2001; 10: 779–87PubMedCrossRefGoogle Scholar
  26. 26.
    National Institute for Health and Clinical Excellence (NICE). Guide to the methods of technology appraisal. London: NICE, 2008 Jun: sections [online]. Available from URL: [Accessed 2010 Apr 23]Google Scholar
  27. 27.
    Malmstrom K, Rodriguez-Gomez G, Guerra J, et al. Oral montelukast, inhaled beclomethasone, and placebo for chronic asthma: a randomized, controlled trial. Montelukast/Beclomethasone Study Group. Ann Intern Med 1999; 130: 487–95PubMedGoogle Scholar
  28. 28.
    Zeiger RS, Szefler SJ, Phillips BR, et al. Response profiles to fluticasone and montelukast in mild-to-moderate persistent childhood asthma. J Allergy Clin Immunol 2006; 117: 45–52PubMedCrossRefGoogle Scholar
  29. 29.
    Donders AR, van der Heijden GJ, Stijnen T, et al. Review: a gentle introduction to imputation of missing values. J Clin Epidemiol 2006; 59 (10): 1087–91PubMedCrossRefGoogle Scholar
  30. 30.
    Rice DP, Cooper BS. The economic value of human life. Am J Public Health Nations Health 1967; 57 (11): 1954–66PubMedCrossRefGoogle Scholar
  31. 31.
    Koopmanschap MA, Rutten FF, van Ineveld BM, et al. The friction costmethod for measuring indirect costs of disease. J Health Econ 1995; 14 (2): 171–89PubMedCrossRefGoogle Scholar
  32. 32.
    Johannesson M, Karlsson G. The friction cost method: a comment. J Health Econ 1997; 16 (2): 249–55PubMedCrossRefGoogle Scholar
  33. 33.
    Koopmanschap MA, Rutten FF, van Ineveld BM, et al. Reply to Johannesson’s and Karlsson’s comment. J Health Econ 1997; 16 (2): 257–59CrossRefGoogle Scholar
  34. 34.
    Pickard AS, Wilke C, Jung E, et al. Use of a preferencebased measure of health (EQ-5D) in COPD and asthma. Respir Med 2008; 102: 519–36PubMedCrossRefGoogle Scholar
  35. 35.
    Szende A, Leidy NK, Stahl E, et al. Estimating health utilities in patients with asthma and COPD: evidence on the performance of EQ-5D and SF-6D. Qual Life Res 2009; 18: 267–72PubMedCrossRefGoogle Scholar
  36. 36.
    Szende A, Svensson K, Stahl E, et al. Psychometric and utility-based measures of health status of asthmatic patients with different disease control level. Pharmacoeconomics 2004; 22 (8): 537–47PubMedCrossRefGoogle Scholar
  37. 37.
    Heaton PC. Cost effectiveness of leukotriene modifiers in adults with asthma. Pharmacoeconomics 2006; 24 (8): 727–42PubMedCrossRefGoogle Scholar
  38. 38.
    Bukstein DA, Henk HJ, Luskin AT. A comparison of asthma-related expenditures for patients started on montelukast versus fluticasone propionate as monotherapy. Clin Ther 2001; 23: 1589–600PubMedCrossRefGoogle Scholar
  39. 39.
    Stempel DA, Mauskopf J, McLaughlin T, et al. Comparison of asthma costs in patients starting fluticasone propionate compared to patients starting montelukast. Respir Med 2001; 95: 227–34PubMedCrossRefGoogle Scholar
  40. 40.
    Allen-Ramey FC, Anstatt DT, Sajjan SG, et al. Asthmarelated health care resource use among patients starting fluticasone or montelukast therapy. Pharmacotherapy 2005; 25: 1752–60PubMedCrossRefGoogle Scholar
  41. 41.
    Balkrishnan R, Nelsen LM, Kulkarni AS, et al. Outcomes associated with initiation of different controller therapies in a Medicaid asthmatic population: a retrospective data analysis. J Asthma 2005; 42: 35–40PubMedCrossRefGoogle Scholar
  42. 42.
    Stempel DA, Meyer JW, Stanford RH, et al. One-year claims analysis comparing inhaled fluticasone propionate with zafirlukast for the treatment of asthma. J Allergy Clin Immunol 2001; 107: 94–8PubMedCrossRefGoogle Scholar
  43. 43.
    Colice GL, Yu AP, Ivanova JI, et al. Costs and resource use of mild persistent asthma patients initiated on controller therapy. J Asthma 2008; 45: 293–9PubMedCrossRefGoogle Scholar
  44. 44.
    O’Connor RD, Parasuraman B, Roberts C, et al. Inhaled corticosteroids vs leukotriene receptor antagonists: health care costs across varying asthma severities. Ann Allergy Asthma Immunol 2006; 97: 236–43PubMedCrossRefGoogle Scholar
  45. 45.
    Barnes PJ, Jonsson B, Klim JB. The costs of asthma. Eur Respir J 1996; 9: 636–42PubMedCrossRefGoogle Scholar
  46. 46.
    Van Ganse E, Laforest L, Pietri G, et al. Persistent asthma: disease control, resource utilisation and direct costs. Eur Respir J 2002; 20: 260–7PubMedCrossRefGoogle Scholar
  47. 47.
    Weiss KB, Sullivan SD. The health economics of asthma and rhinitis: I. Assessing the economic impact. J Allergy Clin Immunol 2001; 107: 3–8PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

  • Edward C. F. Wilson
    • 1
    Email author
  • Erika J. Sims
    • 1
  • Stanley D. Musgrave
    • 1
  • Lee Shepstone
    • 1
  • Annie Blyth
    • 1
  • Jamie Murdoch
    • 1
  • H. Miranda Mugford
    • 1
  • Elizabeth F. Juniper
    • 2
  • Jon G. Ayres
    • 3
  • Stephanie Wolfe
    • 4
  • Daryl Freeman
    • 5
    • 6
  • Richard F. T. Gilbert
    • 7
  • Ian Harvey
    • 1
  • Elizabeth V. Hillyer
    • 8
  • David Price
    • 1
    • 5
  1. 1.Health Economics Group, Faculty of HealthUniversity of East AngliaNorwichUK
  2. 2.Department of Clinical Epidemiology and BiostatisticsMcMaster UniversityHamiltonCanada
  3. 3.Institute of Occupational and Environmental MedicineDivision of Public Health and Epidemiology, University of BirminghamBirminghamUK
  4. 4.Thorpewood SurgeryNorwichUK
  5. 5.Centre of Academic Primary CareUniversity of AberdeenAberdeenUK
  6. 6.Sheringham Medical PracticeSheringhamUK
  7. 7.Castle PartnershipNorwichUK
  8. 8.Research in Real Life LtdCawstonUK

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