Budesonide/Formoterol Maintenance and Reliever Therapy in Asian Patients (Aged ≥16 Years) with Asthma: A Sub-Analysis of the COSMOS Study

Clinical Drug Investigation, 06/12/2012

Vogelmeier C et al. – 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.

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) μg/day, respectively, in patients using maintenance plus as–needed budesonide/formoterol compared with salmeterol/fluticasone propionate.

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