Donald A Mahler1, Edward Kerwin2, Lindsey Murray3, Carole Dembek4. 1. Geisel School of Medicine at Dartmouth, Hanover, New Hampshire. 2. Clinical Research Institute of Southern Oregon, Medford, Oregon. 3. Evidera, Bethesda, Maryland. 4. Sunovion Pharmaceuticals Inc., Marlborough, Massachusetts.
Abstract
BACKGROUND: Chronic cough, dyspnea, and excessive sputum production, the characteristic symptoms of chronic obstructive pulmonary disease (COPD), can negatively affect patients' health-related quality of life (HRQoL). The fixed-dose combination of a long-acting beta2-adrenergic agonist and a long-acting muscarinic antagonist (LABA/LAMA) have been shown to improve HRQoL and COPD symptoms as measured by the St George's Respiratory Questionnaire (SGRQ) and the Transition Dyspnea Index (TDI) total scores. However, the impact of a LABA/LAMA on the individual components of HRQoL and dyspnea with daily activities is unknown. METHODS: Secondary analysis of pooled data from 2 replicate, phase 3, 12-week, randomized, placebo, and active-controlled trials of twice-daily indacaterol/glycopyrrolate (IND/GLY) were analyzed. Change from baseline in HRQoL and dyspnea was measured by SGRQ and TDI, respectively. Total and component scores were evaluated using linear mixed models. Logistic regression was used to analyze the proportion of patients achieving minimum clinically important difference. Study outcomes were further explored in patient subgroups. RESULTS: A total of 2038 patients from FLIGHT1/FLIGHT2 studies were evaluated. IND/GLY significantly improved SGRQ component scores (symptoms [-7.3], activity [-3.6], and impacts [-5.0]); all P < 0.001 compared with placebo. IND/GLY also significantly improved symptoms scores compared with IND and GLY (-3.5 and -3.7, respectively; both P < 0.001). Patients treated with IND/GLY also had significant improvements in TDI component scores compared with placebo: functional impairment (0.48), magnitude of task (0.61), and magnitude of effort (0.54); all P < 0.001. All component scores were significantly higher for IND/GLY compared with IND and GLY (P ≤ 0.002 for all). CONCLUSIONS: Twice-daily IND/GLY significantly improved total scores as well as components of HRQoL and dyspnea in patients with COPD. These data demonstrate multiple clinical benefits of LABA/LAMA maintenance therapy in the COPD population. ClinicalTrials.gov: NCT01727141 and NCT01712516. JCOPDF
BACKGROUND: Chronic cough, dyspnea, and excessive sputum production, the characteristic symptoms of chronic obstructive pulmonary disease (COPD), can negatively affect patients' health-related quality of life (HRQoL). The fixed-dose combination of a long-acting beta2-adrenergic agonist and a long-acting muscarinic antagonist (LABA/LAMA) have been shown to improve HRQoL and COPD symptoms as measured by the St George's Respiratory Questionnaire (SGRQ) and the Transition Dyspnea Index (TDI) total scores. However, the impact of a LABA/LAMA on the individual components of HRQoL and dyspnea with daily activities is unknown. METHODS: Secondary analysis of pooled data from 2 replicate, phase 3, 12-week, randomized, placebo, and active-controlled trials of twice-daily indacaterol/glycopyrrolate (IND/GLY) were analyzed. Change from baseline in HRQoL and dyspnea was measured by SGRQ and TDI, respectively. Total and component scores were evaluated using linear mixed models. Logistic regression was used to analyze the proportion of patients achieving minimum clinically important difference. Study outcomes were further explored in patient subgroups. RESULTS: A total of 2038 patients from FLIGHT1/FLIGHT2 studies were evaluated. IND/GLY significantly improved SGRQ component scores (symptoms [-7.3], activity [-3.6], and impacts [-5.0]); all P < 0.001 compared with placebo. IND/GLY also significantly improved symptoms scores compared with IND and GLY (-3.5 and -3.7, respectively; both P < 0.001). Patients treated with IND/GLY also had significant improvements in TDI component scores compared with placebo: functional impairment (0.48), magnitude of task (0.61), and magnitude of effort (0.54); all P < 0.001. All component scores were significantly higher for IND/GLY compared with IND and GLY (P ≤ 0.002 for all). CONCLUSIONS: Twice-daily IND/GLY significantly improved total scores as well as components of HRQoL and dyspnea in patients with COPD. These data demonstrate multiple clinical benefits of LABA/LAMA maintenance therapy in the COPD population. ClinicalTrials.gov: NCT01727141 and NCT01712516. JCOPDF
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