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Single-Inhaler Combination Therapy for Asthma

A Review of Cost Effectiveness

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Abstract

Clinical studies have shown that the combination of an inhaled corticosteroid (ICS) and a long-acting ß2-adrenoceptor agonist (LABA) for patients with asthma is more effective than the use of ICS alone in equivalent or higher doses, as well as the use of other combinations. However, the relatively higher acquisition costs for the combination therapy require assessment of the value of the incremental costs, especially from a societal perspective. This review provides an overall assessment of the cost effectiveness of ICS plus LABA combination therapy for asthma. A systematic literature research was conducted in MEDLINE to identify studies published between January 1994 and September 2005.

Cost-effectiveness studies derived from 11 clinical studies were identified. The ICS plus LABA combination was compared with ICS alone in eight studies, ICS plus a leukotriene antagonist in two studies, and a leukotriene antagonist alone in one study. All studies focused on measuring direct medical costs in a total of six different healthcare systems, and three studies conducted sensitivity analyses, including productivity costs. Outcomes were measured in treatment success (changes in lung function), episode-free days, and symptom-free days by evaluating short-term follow-up.

The combination of ICS and LABA was found to be more efficacious and cost effective compared with ICS alone or alternative combinations of controller medications. Further considerations for measuring long-term outcomes and dose-response relationships might be required to provide further evidence on the cost effectiveness of combination therapy with ICS plus LABA.

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  1. The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. Greening AP, Ind PW, Northfield M, et al. Added salmeterol versus higher-dose corticosteroid in asthma patients with symptoms. Lancet 1994; 334: 219–224

    Article  Google Scholar 

  2. Woolcock A, Lundback B, Ringdal N, et al. Comparison of addition of salmeterol to inhaled steroids with doubling the dose of inhaled steroids. Am J Respir Crit Care Med 1996; 153: 1481–1488

    PubMed  CAS  Google Scholar 

  3. Shrewsbury S, Pyke S, Britton M. Meta-analysis of increased dose of inhaled steroid or addition of inhaled salmeterol in symptomatic asthma (MIASMA). BMJ 2000; 320: 1368–1373

    Article  PubMed  CAS  Google Scholar 

  4. Ind PW, Negro RD, Colman NC, et al. Addition of salmeterol to fluticasone propionate treatment in moderate-to-severe asthma. Respir Med 2003; 97: 555–562

    Article  PubMed  CAS  Google Scholar 

  5. Pauwels RA, Löfdahl C-G, Postma DS, et al. Effect of inhaled formoterol and budesonide on exacerbations of asthma. N Engl J Med 1997; 337: 1405–1411

    Article  PubMed  CAS  Google Scholar 

  6. O’Byrne PM, Barnes PJ, Rodriguez-Roisin R, et al. Low dose inhaled budesonide and formoterol in mild persistent asthma: the OPTIMA randomized trial. Am J Respir Crit Care Med 2001; 164: 1392–1397

    PubMed  Google Scholar 

  7. 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: 234–241

    Article  PubMed  CAS  Google Scholar 

  8. Nelson H, 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: 1088–1095

    Article  PubMed  CAS  Google Scholar 

  9. NIH. Guidelines for the diagnosis and management of asthma. Bethesda (MD): US Department of Health and Human Services, National Institutes of Health, 1997 Apr. NIH publication no. 97-4051

    Google Scholar 

  10. Global strategy for asthma management and prevention. National Institutes of Health and National Heart, Lung and Blood Institute, Revised 2002 [online]. Available from URL: http://www.ginasthma.com [Accessed 2006 Apr 16]

  11. Masoli M, Holt S, Weatherall M, et al. Dose-response relationship of inhaled budesonide in adult asthma: a meta-analysis. Eur Respir J 2004; 23: 552–558

    Article  PubMed  CAS  Google Scholar 

  12. Holt S, Suder A, Weatherall M, et al. Dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma: meta-analysis. BMJ 2001 Aug 4; 323 (7307): 253–256

    Article  PubMed  CAS  Google Scholar 

  13. NHLBI. Guidelines for the diagnosis and management of asthma. Bethesda (MD): National Asthma Education Program, National Heart, Lung and Blood Institute, 1991 Aug. Publication no. 91-3042

    Google Scholar 

  14. Jarjour N, Laviolette M, Moore W, et al. Control of airway inflammation and remodeling during a 60% reduction in ICS dose with fluticasone propionate/salmeterol (FSC): comparison with higher dose fluticasone propionate (FP) alone [abstract]. Am J Respir Crit Care Med 2004; 169 (7): A451

    Google Scholar 

  15. Kavuru M, Melamed J, Gross G, et al. Salmeterol and fluticasone propionate combined in a new powder inhalation device for the treatment of asthma: a randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol 2000; 105: 1108–1116

    Article  PubMed  CAS  Google Scholar 

  16. Shapiro G, Lumry W, Wolfe J, et al. Combined salmeterol 50μg and fluticasone propionate 250μg in the Diskus device for the treatment of asthma. Am J Respir Crit Care Med 2000; 161: 527–534

    PubMed  CAS  Google Scholar 

  17. Persson U, Ghatnekas O. Cost-effectiveness analysis of inhaled corticosteroids in asthma: a review of analytical standards. Respir Med 2003; 97: 1–11

    Article  PubMed  CAS  Google Scholar 

  18. Stempel DA, Fuhlbrigge AL. Defining the responder in asthma therapy. J Allergy Clin Immunol 2005; 115: 466–469

    Article  PubMed  Google Scholar 

  19. Donaldson C, Currie G, Mitton C. Cost effectiveness analysis in health care: contraindications. BMJ 2002; 325: 891–894

    Article  PubMed  Google Scholar 

  20. Johansson G, Price MJ, Sondhi S. Cost-effectiveness analysis of salmeterol/fluticasone propionate 50/100μg vs fluticasone propionate 100μg in adults and adolescents with asthma III: results. Pharmacoeconomics 1999; 16 Suppl. 2: 15–21

    Article  CAS  Google Scholar 

  21. Palmqvist M, Price MJ, Sondhi S. Cost-effectiveness analysis of salmeterol/fluticasone propionate 50/250μg vs fluticasone propionate 250μg in adults and adolescents with asthma IV: results. Pharmacoeconomics 1999; 16 Suppl. 2: 23–28

    Article  CAS  Google Scholar 

  22. Pieters WR, Lundbäck B, Sondhi S, et al. Cost-effectiveness analysis of salmeterol/fluticasone propionate 50/500μg vs fluticasone propionate 500μg in patients with corticosteroid-dependent asthma v: results. Pharmacoeconomics 1999; 16 Suppl. 2: 29–34

    Article  CAS  Google Scholar 

  23. Andersson F, Ståhl E, Barnes PJ, et al. Adding formoterol to budesonide in moderate asthma: health economic results from the FACET study. Respir Med 2001; 95 (6): 505–512

    Article  PubMed  CAS  Google Scholar 

  24. Jönsson B, Berggren F, Svensson K, et al. An economic evaluation of combination treatment with budesonide and formoterol in patients with mild-to-moderate persistent asthma. Respir Med 2004; 98 (11): 1146–1154

    Article  PubMed  Google Scholar 

  25. Price D, Haughney J, Lloyd A, et al. An economic evaluation of adjustable and fixed dosing with budesonide/formoterol via a single inhaler in asthma patients: the ASSURE study. Curr Med Res Opin 2004; 20 (10): 1671–1679

    Article  PubMed  Google Scholar 

  26. Brüggenjürgen B, Selim D, Kardos P, et al. Economic assessment of adjustable maintenance treatment with budesonide/formoterol in a single inhaler versus fixed treatment in asthma. Pharmacoeconomics 2005; 23 (7): 723–731

    Article  PubMed  Google Scholar 

  27. Lundbäck B, Jenkin C, Price MJ, et al. Cost-effectiveness of salmeterol/fluticasone propionate combination product 50/250μg twice daily and budesonide 800μg twice daily in the treatment of adults and adolescents with asthma. Respir Med 2000; 94 (7): 724–732

    Article  PubMed  Google Scholar 

  28. Sheth K, Borker R, Emmett A, et al. Cost-effectiveness comparison of salmeterol/fluticasone propionate versus montelukast in the treatment of adults with persistent asthma. Pharmacoeconomics 2002; 20 (13): 909–918

    Article  PubMed  Google Scholar 

  29. Pieters WR, Wilson KK, Smith HCE, et al. Salmeterol/fluticasone propionate versus fluticasone propionate plus montelukast: a cost-effective comparison for asthma. Treat Respir Med 2005; 4 (2): 129–138

    Article  PubMed  CAS  Google Scholar 

  30. 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): 815–825

    Article  PubMed  Google Scholar 

  31. 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: 433–439

    Article  PubMed  CAS  Google Scholar 

  32. 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: 1028–1035

    Article  PubMed  Google Scholar 

  33. 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 Feb; 42 (1): 35–40

    Article  PubMed  Google Scholar 

  34. Aubier M, Pieters WR, Schlösser NJJ, et al. Salmeterol/fluticasone propionate (50/500μg) in combination in a Diskus inhaler (Seretide) is effective and safe in the treatment of steroid-dependent asthma. Respir Med 1999; 93: 876–884

    Article  PubMed  CAS  Google Scholar 

  35. Ind PW, Haughney J, Price D, et al. Adjustable and fixed dosing with budesonide/formoterol via a single inhaler in asthma patients: the ASSURE study. Respir Med 2004; 98: 464–475

    Article  PubMed  CAS  Google Scholar 

  36. Buhl R, Kardos P, Baare A, et al. Adjustable dosing with budesonide/formoterol in asthma maintains HRQL at a lower drug load than fixed dosing. Curr Med Res Opin 2004; 20: 1209–1220

    Article  PubMed  CAS  Google Scholar 

  37. Jenkins C, Woolcock AJ, Saarelainen P, et al. Salmeterol/fluticasone propionate combination therapy 50/250μg twice daily is more effective than budesonide 800μg twice daily in treating moderate to severe asthma. Respir Med 2000; 94: 715–723

    Article  PubMed  CAS  Google Scholar 

  38. Calhoun WJ, Nelson HS, Nathan RA, et al. Comparison of fluticasone propionate-salmeterol combination therapy and montelukast in patients who are symptomatic on short acting â2 agonists alone. Am J Respir Crit Care Med 2001; 164: 759–763

    PubMed  CAS  Google Scholar 

  39. Nelson HS, Chapman KR, Pyke SD, et al. Enhanced synergy between fluticasone propionate and salmeterol inhaled from a single inhaler versus separate inhalers. J Allergy Clin Immunol 2003; 112: 29–36

    Article  PubMed  CAS  Google Scholar 

  40. Stempel DA, Stoloff SW, Carranza Rosenzweig JR, et al. Adherence to asthma controller medication regimens. Respir Med 2005; 99: 1263–1267

    Article  PubMed  CAS  Google Scholar 

  41. Stoloff SW, Stempel DA, Meyer J, et al. Improved refill persistence with fluticasone propionate and salmeterol in a single inhaler compared with other controller therapies. J Allergy Clin Immunol 2004; 113: 245–251

    Article  PubMed  Google Scholar 

  42. Reddel HK, Jenkins CR, Marks GB, et al. Optimal asthma control, starting with high doses of inhaled budesonide. Eur Respir J 2000; 16: 226–235

    Article  PubMed  CAS  Google Scholar 

  43. The Childhood Asthma Management Program Research Group. The long-term effects of budesonide or nedocromil in children with asthma. N Engl J Med 2000; 343: 1054–1063

    Article  Google Scholar 

  44. Pauwels RA, Pedersen S, Busse WW, et al. Early intervention with budesonide in mild persistent asthma: a randomized, double-blind trial. Lancet 2003; 361: 1071–1076

    Article  PubMed  CAS  Google Scholar 

  45. Bateman ED, Boushey HA, Bousquet J, et al. Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma controL study. Am J Respir Crit Care Med 2004; 170 (8): 836–844

    Article  PubMed  Google Scholar 

  46. Fitzgerald JM, Boulet LP, Fellows RMA. The CONCEPT trial: a 1-year, multicenter, randomized, double-blind, double-dummy comparison of a stable dosing regimen of salmeterol/ fluticasone propionate with an adjustable dosing regimen of formoterol/budesonide in adults with persistent asthma. Clin Ther 2005; 27: 393–406

    Article  PubMed  CAS  Google Scholar 

  47. Goetzel RZ, Long SR, Ozminkowski RJ, et al. Health, absence, disability, and presenteeism cost estimates of certain physical and mental health conditions affecting U.S. employers. J Occup Environ Med 2004; 46: 398–412

    Article  PubMed  Google Scholar 

  48. Boushey HA, Sorkness CA, King TS, et al. Daily versus as-needed corticosteroids for mild persistent asthma. N Engl J Med 2005; 352: 1519–1528

    Article  PubMed  CAS  Google Scholar 

  49. National Compensation Survey. Occupational wages in the United States, July 2004 [online]. Available from URL: http://www.bls.gov/ncs/ocs/sp/ncbl0727.pdf [Accessed2005 Sep 9]

  50. Buxton M, Sullivan SD, Andersson LF, et al. Country-specific cost-effectiveness of early intervention with budesonide in mild asthma. Eur Respir J 2004; 24: 568–574

    Article  PubMed  CAS  Google Scholar 

  51. Sullivan SD, Buxton M, Andersson LF, et al. Cost-effectiveness analysis of early intervention with budesonide in mild persistent asthma. J Allergy Clin Immunol 2003; 112 (6): 1229–1236

    Article  PubMed  Google Scholar 

  52. Boushey HA. Daily inhaled corticosteroid treatment should not be prescribed for mild persistent asthma. Am Rev Respir Dis 2005; 172: 412–414

    Article  Google Scholar 

  53. Lim, Jatyakanon A, Gordon D, et al. Comparison of high dose inhaled steroids, low dose inhaled steroids plus theophylline, and low dose inhaled corticosteroids alone in chronic asthma in general practice. Thorax 2000; 55: 837–841

    Article  PubMed  CAS  Google Scholar 

  54. Price D, Hernandez D, Magyar P, et al. Randomized controlled trial of montelukast plus inhaled budesonide versus double dose inhaled budesonide in adult patients with asthma. Thorax 2003; 58: 211–216

    Article  PubMed  CAS  Google Scholar 

  55. Yildirim Z, Ozlu T, Bulbul Y, et al. Addition of montelukast versus double dose of inhaled budesonide in moderate persistent asthma. Respirology 2004; 9: 243–248

    Article  PubMed  Google Scholar 

  56. Fitzgerald JM, Becker A, Sear MR, et al. Doubling the dose of budesonide versus maintenance treatment in asthma exacerbations. Thorax 2004; 59: 550–556

    Article  PubMed  CAS  Google Scholar 

  57. Harrison TW, Osborn J, Newton S, et al. Doubling the dose of inhaled corticosteroid toprevent asthma exacerbations: randomized controlled trials. Lancet 2004; 363: 271–275

    Article  PubMed  CAS  Google Scholar 

  58. O’Byrne PM, Bisgaard H, Godard PP, et al. Budesonide/ formoterol combination therapy as both maintenance and reliever medication in asthma. Am J Respir Crit Care Med 2005; 17: 129–136

    Google Scholar 

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Acknowledgements

David A. Stempel is a consultant and on the speaker’s bureau for GlaxoSmithKline, Research Triangle Park, NC, USA. Manabu Akazawa is a Fellow, Global Health Outcomes at GlaxoSmithKline. Both authors made substantial contributions to the intellectual content of the paper.

No sources of funding were used to assist in the preparation of this review.

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Authors and Affiliations

  1. Department of Health Policy and Administration, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

    Manabu Akazawa

  2. Infomed Northwest, Bellevue, Washington, 98004, USA

    David A. Stempel

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  1. Manabu Akazawa
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  2. David A. Stempel
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Correspondence to David A. Stempel.

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Akazawa, M., Stempel, D.A. Single-Inhaler Combination Therapy for Asthma. Pharmacoeconomics 24, 971–988 (2006). https://doi.org/10.2165/00019053-200624100-00005

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