, Volume 28, Issue 7, pp 597–608 | Cite as

Cost Effectiveness of Leukotriene Receptor Antagonists versus Long-Acting Beta-2 Agonists as Add-On Therapy to Inhaled Corticosteroids for Asthma

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


Background: Information is lacking on the relative effectiveness and cost effectiveness — in a real-life primary-care setting — of leukotriene receptor antagonists (LTRAs) and long-acting β2 adrenergic receptor agonists (β2 agonists) as add-on therapy for patients whose asthma symptoms are not controlled on low-dose inhaled corticosteroids (ICS).

Objective: To estimate the cost effectiveness of LTRAs compared with longacting β2 agonists as add-on therapy for patients whose asthma symptoms are not controlled on low-dose ICS.

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 insufficiently controlled with ICS (n = 361) were randomly assigned to add-on LTRAs (n = 176) or long-acting β2 agonists (n = 185). The main outcome measures were the incremental cost per point improvement in the Mini Asthma Quality of Life Questionnaire (MiniAQLQ), per point improvement in the Asthma Control Questionnaire (ACQ) and per QALY gained from perspectives of the UK NHS and society.

Results: Over 2 years, the societal cost per patient receiving LTRAs was £1157 versus £952 for long-acting b2 agonists, a (significant, adjusted) increase of d214 (95%CI 2, 411) [year 2005 values]. Patients receiving LTRAs experienced a non-significant incremental gain of 0.009 QALYs (95% CI −0.077, 0.103). The incremental cost per QALY gained from the societal (NHS) perspective was £22 589 (£11 919). Uncertainty around this point estimate suggested that, given a maximum willingness to pay of £30 000 per QALY gained, the probability that LTRAs are a cost-effective alternative to long-acting β2 agonists as add-on therapy was approximately 52% from both societal and NHS perspectives.

Conclusions: On balance, these results marginally favour the repositioning of LTRAs as a cost-effective alternative to long-acting β2 agonists as add-on therapy to ICS for asthma. However, there is much uncertainty surrounding the incremental cost effectiveness because of similarity of clinical benefit and broad confidence intervals for differences in healthcare costs.

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


Asthma Montelukast Zafirlukast Supplemental Digital Content Point Improvement 
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 & Respiratory Research Group, Division of Community Health Sciences, University of Edinburgh) 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 Respiratory Research 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_28070597_MOESM1_ESM.pdf (248 kb)
Supplementary material, approximately 254 KB.


  1. 1.
    Masoli M, Fabian D, Holt S, et al. The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy 2004; 59: 469–78PubMedCrossRefGoogle Scholar
  2. 2.
    Barnes PJ, Jonsson B, Klim JB. The costs of asthma. Eur Respir J 1996; 9: 636–42PubMedCrossRefGoogle Scholar
  3. 3.
    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
  4. 4.
    Rabe KF, Adachi M, Lai CK, et al. Worldwide severity and control of asthma in children and adults: the global asthma insights and reality surveys. J Allergy Clin Immunol 2004; 114: 40–7PubMedCrossRefGoogle Scholar
  5. 5.
    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
  6. 6.
    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
  7. 7.
    Global Initiative for Asthma. GINA report, global strategy for asthma management and prevention [online]. Available from URL: [Accessed 2010 Apr 23]
  8. 8.
    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
  9. 9.
    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
  10. 10.
    Lemanske RF, Mauger DT, Sorkness C, et al. Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. N Engl J Med 2010; 362 (11): 975–85PubMedCrossRefGoogle Scholar
  11. 11.
    De Maeseneer JM, van Driel ML, Green LA, et al. The need for research in primary care. Lancet 2003; 362: 1314–9PubMedCrossRefGoogle Scholar
  12. 12.
    Price D, Thomas M. Breaking new ground: challenging existing asthma guidelines. BMC Pulm Med 2006; 6 Suppl. 1: S6CrossRefGoogle Scholar
  13. 13.
    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
  14. 14.
    British National Formulary. 50th ed. London: British Medical Association and the Royal Pharmaceutical Society of Great Britain, 2005Google Scholar
  15. 15.
    Department of Health. NHS reference costs 20042005: appendix 4 [online]. Available from URL: [Accessed 2010 Apr 23]
  16. 16.
    Office for National Statistics. Annual Survey of Hours and Earnings (ASHE). 2005 [online]. Available from URL: [Accessed 2010 Apr 23]Google Scholar
  17. 17.
    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]
  18. 18.
    HM Treasury. The green book: appraisal and evaluation in central government. London: HM Treasure: section 5.49 [online]. Available from URL: [Accessed 2010 Apr 23]
  19. 19.
    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
  20. 20.
    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
  21. 21.
    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
  22. 22.
    The EuroQol Group. EuroQol: a new facility for the measurement of health-related quality of life. Health Policy 1990; 16: 199–208CrossRefGoogle Scholar
  23. 23.
    Brooks R. EuroQol: the current state of play. Health Policy 1996; 37: 53–72PubMedCrossRefGoogle Scholar
  24. 24.
    Dolan P. Modeling valuations for EuroQol health states. Med Care 1997; 35: 1095–108PubMedCrossRefGoogle Scholar
  25. 25.
    Drummond MF, Sculpher MJ, Torrance GW, et al. Quality adjusted life years. In: Drummond MF, Sculpher MJ, Torrance GW, et al., editors. Methods for the economic evaluation of health care programmes. 3rd ed. Oxford: Oxford University Press, 2005: 173–88Google Scholar
  26. 26.
    Rubin DB. Multiple imputation for nonresponse in surveys. Hoboken (NJ): John Wiley & Sons, 1987CrossRefGoogle Scholar
  27. 27.
    Fenwick E, Claxton K, Sculpher M. Representing uncertainty: the role of cost-effectiveness acceptability curves. Health Econ 2001; 10: 779–87PubMedCrossRefGoogle Scholar
  28. 28.
    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
  29. 29.
    Lima JJ, Zhang S, Grant A, et al. Influence of leukotriene pathway polymorphisms on response to montelukast in asthma. Am J Respir Crit Care Med 2006; 173: 379–85PubMedCrossRefGoogle Scholar
  30. 30.
    Litonjua AA. The significance of beta2-adrenergic receptor polymorphisms in asthma. Curr Opin Pulm Med 2006; 12: 12–7PubMedCrossRefGoogle Scholar
  31. 31.
    Claxton K. The irrelevance of inference: a decision-making approach to the stochastic evaluation of health care technologies. J Health Econ 1999; 18: 341–64PubMedCrossRefGoogle Scholar
  32. 32.
    Briggs AH. New methods of analysing cost effectiveness. BMJ 2007; 335: 622–3PubMedCrossRefGoogle Scholar
  33. 33.
    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
  34. 34.
    Pieters WR, Wilson KK, Smith HC, et al. Salmeterol/fluticasone propionate versus fluticasone propionate plus montelukast: a cost-effective comparison for asthma. Treat Respir Med 2005; 4: 129–38PubMedCrossRefGoogle Scholar
  35. 35.
    O’Connor RD, Nelson H, Borker R, et al. Cost effectiveness of fluticasone propionate plus salmeterol versus fluticasone propionate plus montelukast in the treatment of persistent asthma. Pharmacoeconomics 2004; 22 (12): 815–25PubMedCrossRefGoogle Scholar
  36. 36.
    Storms W. Clinical trials: are these your patients? J Allergy Clin Immunol 2003; 112: S107–11CrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

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

Personalised recommendations