Stefan M Frent1,2, Kenneth R Chapman3, Michael Larbig4, Alexander Mackay2,5, Robert Fogel6, Florian S Gutzwiller4, Steven Shen6, Francesco Patalano4, Donald Banerji6, Konstantinos Kostikas4, Jadwiga A Wedzicha5,7. 1. 1 Department of Pulmonology, University of Medicine and Pharmacy Timisoara, Timisoara, Romania. 2. 2 European Respiratory Society Fellow at Novartis Pharma AG, Basel, Switzerland. 3. 3 Department of Medicine, Asthma and Airway Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada. 4. 4 Novartis Pharma AG, Basel, Switzerland. 5. 5 National Heart and Lung Institute, Imperial College London, London, United Kingdom. 6. 6 Novartis Pharmaceuticals Corporation, East Hanover, New Jersey; and. 7. 7 Editor-In-Chief, AJRCCM.
Abstract
RATIONALE: Chronic obstructive pulmonary disease exacerbations accelerate lung function decline, reduce quality of life, and increase mortality. A subset of patients (n = 457) from the FLAME (Effect of Indacaterol Glycopyrronium vs. Fluticasone Salmeterol on COPD Exacerbations) study used the Exacerbations of COPD Tool (EXACT) to capture symptom-defined exacerbations. OBJECTIVES: To evaluate the effect of indacaterol/glycopyrronium versus salmeterol/fluticasone on symptom-defined exacerbations measured using EXACT, and to assess differences between these events and exacerbations requiring healthcare resource use (HCRU). METHODS: All patients in FLAME used an electronic diary to record and detect symptom deteriorations; HCRU-related exacerbations were confirmed by investigators. In patients using the EXACT questionnaire, the onset, recovery, and magnitude of symptom-defined exacerbations were identified by changes in total scores relative to baseline. We analyzed the annualized rate and time to first symptom-defined (EXACT) exacerbation and assessed differences between symptom-defined and HCRU events in terms of number, severity, and concordance. MEASUREMENTS AND MAIN RESULTS: A nonsignificant 17% reduction in the annualized rate of symptom-defined (EXACT) exacerbations (rate ratio, 0.83; 95% confidence interval [CI], 0.60-1.14; P = 0.242) and a numerically longer time to first symptom-defined exacerbation were observed with indacaterol/glycopyrronium versus salmeterol/fluticasone (hazard ratio, 0.76; 95% CI, 0.56-1.03; P = 0.075). These results were consistent with data from the overall FLAME population. Of the symptom-defined (EXACT) events, 23.5% corresponded to HCRU events, and 22.2% of HRCU events were captured by EXACT (κ index, 0.24; 95% CI, 0.15-0.33). CONCLUSIONS: Regardless of the exacerbation definition used, our findings support the use of long-acting β2 agonists/long-acting muscarinic receptor antagonists as the preferred treatment option for patients at risk of future exacerbations. Clinical trial registered with www.clinicaltrials.gov (NCT01782326).
RCT Entities:
RATIONALE: Chronic obstructive pulmonary disease exacerbations accelerate lung function decline, reduce quality of life, and increase mortality. A subset of patients (n = 457) from the FLAME (Effect of Indacaterol Glycopyrronium vs. Fluticasone Salmeterol on COPD Exacerbations) study used the Exacerbations of COPD Tool (EXACT) to capture symptom-defined exacerbations. OBJECTIVES: To evaluate the effect of indacaterol/glycopyrronium versus salmeterol/fluticasone on symptom-defined exacerbations measured using EXACT, and to assess differences between these events and exacerbations requiring healthcare resource use (HCRU). METHODS: All patients in FLAME used an electronic diary to record and detect symptom deteriorations; HCRU-related exacerbations were confirmed by investigators. In patients using the EXACT questionnaire, the onset, recovery, and magnitude of symptom-defined exacerbations were identified by changes in total scores relative to baseline. We analyzed the annualized rate and time to first symptom-defined (EXACT) exacerbation and assessed differences between symptom-defined and HCRU events in terms of number, severity, and concordance. MEASUREMENTS AND MAIN RESULTS: A nonsignificant 17% reduction in the annualized rate of symptom-defined (EXACT) exacerbations (rate ratio, 0.83; 95% confidence interval [CI], 0.60-1.14; P = 0.242) and a numerically longer time to first symptom-defined exacerbation were observed with indacaterol/glycopyrronium versus salmeterol/fluticasone (hazard ratio, 0.76; 95% CI, 0.56-1.03; P = 0.075). These results were consistent with data from the overall FLAME population. Of the symptom-defined (EXACT) events, 23.5% corresponded to HCRU events, and 22.2% of HRCU events were captured by EXACT (κ index, 0.24; 95% CI, 0.15-0.33). CONCLUSIONS: Regardless of the exacerbation definition used, our findings support the use of long-acting β2 agonists/long-acting muscarinic receptor antagonists as the preferred treatment option for patients at risk of future exacerbations. Clinical trial registered with www.clinicaltrials.gov (NCT01782326).
Entities:
Keywords:
concordance; defined symptom; exacerbation; treatment
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