PURPOSE: Fluticasone Propionate/Salmeterol Combination (FSC) and Tiotropium (Tio) are frequently co-prescribed in clinical practice in COPD. However, few studies have examined the effects of combining these medications. This study is the first to examine the effects of FSC (250/50) combined with Tio on outcomes in subjects with COPD.
METHODS: Subjects with COPD with an FEV1 of 40-80% predicted received open-label Tio during a 4-week run-in period. A modified Medical Research Council (mMRC) dyspnea score of 2 or greater was required before subjects could continue on open-label Tio and were randomized to blinded FSC or blinded placebo and open-label Tio for 24 weeks. Outcomes assessed included morning pre-dose FEV1, 2-hour post-dose FEV1, morning pre-dose FVC, 2-hour post-dose FVC, morning pre-dose IC, and scores on the Chronic Respiratory Disease-Self-Administered Standardized (CRQ-SAS).
RESULTS: 342 subjects were randomized (mean post-albuterol FEV1 of 56.7%, mean age of 61.2 years, 47% males, mean mMRC score of 2.5). Triple therapy resulted in a statistically significant improvement in morning pre-dose FEV1 compared to Tio alone (least squares [LS] mean difference of 115 mL, p<0.001) and 2-hour post-dose FEV1 (LS mean difference 154 mL, p<0.001). Other lung function measures were also significantly improved. Health related quality of life (QoL) revealed mild impairment in these groups at baseline (FSC plus Tio group mean baseline domain scores were 4.98 for mastery, 3.91 for fatigue, 4.59 for emotional function, and 4.72 for dyspnea compared to scores of 5.05 for mastery, 3.82 for fatigue, 4.56 for emotional function, and 4.66 for dyspnea in the Tio group) that did not change with treatment.
CONCLUSION: Triple therapy with FSC 250/50 plus Tio was superior to Tio alone in improving a variety of lung function parameters but did not statistically improve QoL.
CLINICAL IMPLICATIONS: Patients with moderate COPD may attain significant physiologic benefits when treatment with FSC 250/50 is added to Tio compared to treatment with Tio alone. (Study ADC111114, NCT 00784550 funded by GlaxoSmithKline).
DISCLOSURE: Nicola Hanania, Shareholder Mike Cicale, Glenn Crater, Dianne O’ Dell, and Amanda Emmett hold shares in GlaxoSmithKline; Employee Mike Cicale, Glenn Crater, Dianne O’ Dell and Amanad Emmett are employees of GlaxoSmithKline; Consultant fee, speaker bureau, advisory committee, etc. N. Hanania has received research grant support/ consultant fees, and is a speaker for GSK, Novartis, Astra Zenecca, Pfizer and Boehringer Ingelheim. D.Niewoehner has received consulting fees from Boehringer Ingelheim, Adams Respiratory Therapeutics, GlaxoSmithKline, AstraZeneca, Nycomed, and Forest Research Institute and speaking fees from Boehringer Ingelheim, Pfizer, Sepracor, and Nycomed.; No Product/Research Disclosure Information