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


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.


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.



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.


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Copyright information

© Springer International Publishing AG 2012

Authors and Affiliations

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

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