Advertisement

Clinical Drug Investigation

, Volume 32, Issue 7, pp 439–449 | Cite as

Budesonide/Formoterol Maintenance and Reliever Therapy in Asian Patients (Aged ≥16 Years) with Asthma

A Sub-Analysis of the COSMOS Study
  • C. Vogelmeier
  • I. Naya
  • J. Ekelund
Original Research Article

Abstract

Background: The combination of an inhaled corticosteroid (ICS), budesonide, and a rapid long-acting β2-agonist (LABA), formoterol, in a single inhaler for use as maintenance and reliever therapy (Symbicort Turbuhaler SMART™) effectively achieves a high level of asthma control and reduces exacerbations and asthma-related hospitalizations. The COSMOS study, a multinational, 12-month study (N = 2143), compared budesonide/formoterol maintenance and reliever therapy with salmeterol/fluticasone propionate plus as-needed salbutamol, allowing physicians to modify maintenance doses of both combinations according to routine clinical practice.

Objective: The aim of this post hoc sub-group analysis of the COSMOS study is to provide focused data on budesonide/formoterol maintenance and reliever therapy compared with salmeterol/fluticasone propionate plus as-needed salbutamol in patients (aged ≥16 years) enrolled across Asian countries, specifically China, Korea, Taiwan and Thailand.

Methods: This sub-analysis of the COSMOS study concerns all 404 randomized patients ≥16 years of age (mean forced expiratory volume in 1 second [FEV1] 69.1%) who were recruited from Asian countries. Patients received either budesonide/formoterol (Symbicort Turbuhaler SMART™, n=198), starting dose 160 mg/4.5 mg two inhalations twice daily (bid) [plus additional as-needed inhalations], or salmeterol/fluticasone propionate (Seretide® Diskus®, n = 206), starting dose 50 mg/250 mg bid (plus salbutamol [Ventolin®] as needed). Maintenance doses could be titrated by clinicians after the first 4 weeks (budesonide/formoterol maintenance plus as needed, n= 198; salmeterol/fluticasone propionate plus salbutamol, n = 206). To allow for free adjustment in maintenance doses in both arms, the trial was performed open-label; maintenance doses could be titrated by clinicians after the first 4 weeks. The time to first severe exacerbation (defined as deterioration in asthma resulting in hospitalization/emergency room treatment, oral corticosteroids for ≥3 days or unscheduled visit leading to treatment change) was the primary variable.

Results: The time to first severe exacerbation was prolonged in patients using maintenance plus as-needed budesonide/formoterol compared with salmeterol/fluticasone propionate plus salbutamol (log-rank p = 0.024). The risk of a first exacerbation was reduced by 44% (hazard ratio 0.56; 95% confidence interval [CI] 0.32, 0.95; p = 0.033) in patients using the adjusted budesonide/formoterol regimen versus titrated salmeterol/fluticasone propionate. The overall exacerbation rates were 0.16 versus 0.26 events/patient-year, respectively, with a 38% reduction (rate ratio 0.62/patient/year; 95% CI 0.41, 0.94; p = 0.024) in favour of the budesonide/formoterol regimen. Compared with baseline, both regimens provided clinically relevant improvements in asthma control, quality of life and FEV1; no statistically significant differences between the treatment groups were observed. Mean adjusted (standard deviation) ICS dose (expressed as beclomethasone dose equivalents) during treatment, including as-needed budesonide doses, was 944 (281) and 1034 (394) mg/day, respectively, in patients using maintenance plus as-needed budesonide/formoterol compared with salmeterol/fluticasone propionate.

Conclusion: In patients (aged ≥16 years) enrolled from Asian countries as part of the COSMOS study, the budesonide/formoterol maintenance and reliever regimen was associated with a lower future risk of exacerbations versus the physicians’ free choice of salmeterol/fluticasone propionate dose plus salbutamol. Single inhaler combination treatment with maintenance plus as-needed budesonide/formoterol was also at least as efficacious as salmeterol/fluticasone propionate dose plus salbutamol in improving current asthma control.

Keywords

Salbutamol Budesonide Fluticasone Propionate Asthma Control Formoterol 
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.

Notes

Acknowledgements

C. Vogelmeier has given presentations at symposia sponsored by AstraZeneca, Boehringer, Chiesi, GlaxoSmithKline, Janssen-Cilag, Novartis, Nycomed, Pfizer and Talecris, and has received consulting fees from AstraZeneca, Boehringer, GlaxoSmithKline, Janssen-Cilag, Mundipharma, Novartis, Nycomed and Talecris. I. Naya and J. Ekelund are employed by AstraZeneca, Sweden. This study was financially supported by AstraZeneca. Medical writing support was provided by Claire Pouwels and Miriam Banner, inScience Communications, Springer Healthcare, which was funded by AstraZeneca.

References

  1. 1.
    Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. 2011Google Scholar
  2. 2.
    Bateman ED, Bousquet J, Braunstein GL. Is overall asthma control being achieved? A hypothesis-generating study. Eur Respir J 2001; 17 (4): 589–95PubMedCrossRefGoogle Scholar
  3. 3.
    Ind PW, Dal Negro R, Colman NC, et al. Addition of salmeterol to fluticasone propionate treatment in moderate-to-severe asthma. Respir Med 2003; 97 (5): 555–62PubMedCrossRefGoogle Scholar
  4. 4.
    Edwards SJ, von Maltzahn R, Naya IP, et al. Budesonide/formoterol for maintenance and reliever therapy of asthma: a meta analysis of randomised controlled trials. Int J Clin Pract 2010; 64 (5): 619–27PubMedCrossRefGoogle Scholar
  5. 5.
    Gibson PG, Powell H, Ducharme FM. Differential effects of maintenance long-acting beta-agonist and inhaled corticosteroid on asthma control and asthma exacerbations. J Allergy Clin Immunol 2007; 119 (2): 344–50PubMedCrossRefGoogle Scholar
  6. 6.
    Palmqvist M, Persson G, Lazer L, et al. Inhaled dry-powder formoterol and salmeterol in asthmatic patients: onset of action, duration of effect and potency. Eur Respir J 1997; 10 (11): 2484–9PubMedCrossRefGoogle Scholar
  7. 7.
    Pauwels RA, Sears MR, Campbell M, et al. Formoterol as relief medication in asthma: a worldwide safety and effectiveness trial. Eur Respir J 2003; 22 (5): 787–94PubMedCrossRefGoogle Scholar
  8. 8.
    Kuna P, Peters MJ, Manjra AI, et al. Effect of budesonide/formoterol maintenance and reliever therapy on asthma exacerbations. Int J Clin Pract 2007; 61 (5): 725–36PubMedCrossRefGoogle Scholar
  9. 9.
    Bousquet J, Boulet LP, Peters MJ, et al. Budesonide/formoterol for maintenance and relief in uncontrolled asthma vs. high-dose salmeterol/fluticasone. Respir Med 2007; 101 (12): 2437–46CrossRefGoogle Scholar
  10. 10.
    Demoly P, Louis R, Soes-Petersen U, et al. Budesonide/formoterol maintenance and reliever therapy versus conventional best practice. Respir Med 2009; 103 (11): 1623–32PubMedCrossRefGoogle Scholar
  11. 11.
    Vogelmeier C, D’Urzo A, Pauwels R, et al. Budesonide/formoterol maintenance and reliever therapy: an effective asthma treatment option? Eur Respir J 2005; 26 (5): 819–28PubMedCrossRefGoogle Scholar
  12. 12.
    Juniper EF, O’Byrne PM, Guyatt GH, et al. Development and validation of a questionnaire to measure asthma control. Eur Respir J 1999; 14 (4): 902–7PubMedCrossRefGoogle Scholar
  13. 13.
    Juniper EF, Buist AS, Cox FM, et al. Validation of a standardized version of the Asthma Quality of Life Questionnaire. Chest 1999; 115 (5): 1265–70PubMedCrossRefGoogle Scholar
  14. 14.
    Pedersen SE, Bateman ED, Bousquet J, et al. Determinants of response to fluticasone propionate and salmeterol/fluticasone propionate combination in the Gaining Optimal Asthma controL study. J Allergy Clin Immunol 2007; 120 (5): 1036–42PubMedCrossRefGoogle Scholar
  15. 15.
    Rabe KF, Atienza T, Magyar P, et al. Effect of budesonide in combination with formoterol for reliever therapy in asthma exacerbations: a randomised controlled, double-blind study. Lancet 2006; 368 (9537): 744–53PubMedCrossRefGoogle Scholar
  16. 16.
    Tattersfield AE, Lofdahl CG, Postma DS, et al. Comparison of formoterol and terbutaline for as-needed treatment of asthma: a randomised trial. Lancet 2001; 357 (9252): 257–61PubMedCrossRefGoogle Scholar
  17. 17.
    Cates CJ, Lasserson TJ. Combination formoterol and budesonide as maintenance and reliever therapy versus inhaled steroid maintenance for chronic asthma in adults and children. Cochrane Database Syst Rev 2009; (2): CD007313Google Scholar
  18. 18.
    Chapman KR, Barnes NC, Greening AP, et al. Single maintenance and reliever therapy (SMART) of asthma: a critical appraisal. Thorax 2010; 65 (8): 747–52PubMedCrossRefGoogle Scholar
  19. 19.
    Riemersma RA, Postma D, van der Molen T. Budesonide/formoterol maintenance and reliever therapy in primary care asthma management: effects on bronchial hyperresponsiveness and asthma control. Prim Care Respir J 2012; 21 (1): 50–6PubMedCrossRefGoogle Scholar
  20. 20.
    Bateman ED, Harrison TW, Quirce S, et al. Overall asthma control achieved with budesonide/formoterol maintenance and reliever therapy for patients on different treatment steps. Respir Res 2011; 12 (38)Google Scholar
  21. 21.
    Quirce S, Barcina C, Plaza V, et al. A comparison of budesonide/formoterol maintenance and reliever therapy versus conventional best practice in asthma management in Spain. J Asthma 2011; 48 (8): 839–47PubMedCrossRefGoogle Scholar
  22. 22.
    Kuna P. Treatment comparison of budesonide/formoterol with salmeterol/fluticasone propionate in adults aged ≥16 years with asthma: post hoc analysis of a randomized, double-blind study. Clin Drug Investig 2010; 30 (9): 565–79PubMedCrossRefGoogle Scholar
  23. 23.
    Aalbers R. Fixed or adjustable maintenance-dose budesonide/formoterol compared with fixed maintenance-dose salmeterol/fluticasone propionate in asthma patients aged ≥16 years: post hoc analysis of a randomized, double-blind/open-label extension, parallel-group study. Clin Drug Investig 2010; 30 (7): 439–51PubMedCrossRefGoogle Scholar
  24. 24.
    Currie GP, Lee DK. The GOAL study: designed to favor a long-acting beta2-agonist? Am J Respir Crit Care Med 2005; 171 (9): 1060–1; author reply 1PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2012

Authors and Affiliations

  1. 1.Marburg University Hospital, BaldingerstrasseMarburgGermany
  2. 2.AstraZenecaMacclesfieldUK
  3. 3.AstraZeneca R&DMölndalSweden

Personalised recommendations