PURPOSE: To compare the effect of fluticasone/salmeterol 250/50mcg BID (FSC) and salmeterol 50mcg BID (SAL) on the annual rate of moderate to severe COPD exacerbations.
METHODS: This was a randomized, double-blind, parallel-group study (Study Code SCO40043). Patients (N=782) were randomized to FSC and SAL for 1 year. During a 4-week run-in, patients received open-label FSC. Patients were ≥ 40 yrs of age with a diagnosis of COPD, an FEV1 of ≤; 50% predicted (mean=32.8%), an FEV1/FVC≤;0.7 and a history of ≥ 1 exacerbation in the past year. Moderate/severe exacerbations were defined as worsening symptoms requiring treatment with oral corticosteroids, antibiotics, or hospitalization.
RESULTS: FSC significantly reduced the annual rate of moderate/severe exacerbations by 30% vs. SAL (annual rates of 1.06 and 1.53, respectively, treatment ratio=0.695, p<0.001), reduced the risk of time to first moderate/severe exacerbation (hazard ratio=0.750, p=0.003) and reduced the annual rate of exacerbations requiring oral corticosteroids (treatment ratio=0.603, p<0.001). During run-in with open-label FSC, mean FEV1 increased by 114 and 118 mL in subjects randomized to FSC and SAL, respectively. During treatment, the mean (SE) difference in pre-dose FEV1 of 47 (22.7) mL significantly favored FSC over SAL (p=0.040 at Endpoint). Change in dyspnea symptom scores, albuterol use, and nighttime awakenings significantly favored FSC. Adverse events were reported for 88% of FSC and 86% of SAL subjects. Pneumonia-related events were reported for 7% and 4% of subjects with FSC and SAL, respectively. The incidence of bone and eye-related events was similar.
CONCLUSION: FSC demonstrated superior efficacy for reduction in moderate/severe COPD exacerbations compared with SAL in subjects with an FEV1 of ≤; 50% of predicted and a history of exacerbations. Over 1 year, FSC was more effective than SAL at maintaining lung function and symptoms. A higher incidence of pneumonias was observed with FSC.
CLINICAL IMPLICATIONS: Treatment with FSC 250/50mcg BID is significantly more effective than salmeterol at reducing the risk of a COPD exacerbation in patients with moderate to severe airway obstruction and a history of exacerbations.
DISCLOSURE: Gary Ferguson, No Product/Research Disclosure Information; Employee Employee of GlaxoSmithKline