Early Clinically Important Improvement (ECII) and Exacerbation Outcomes in COPD Patients

• Published in: International journal of chronic obstructive pulmonary disease Vol. 15; pp. 1831 - 1838
• Main Authors: Kostikas, Konstantinos, Mackay, Alexander J, Vogelmeier, Claus F, Frent, Stefan-Marian, Gupta, Pritam, Banerji, Donald, Patalano, Francesco, Pfister, Pascal J, Wedzicha, Jadwiga A
• Format: Journal Article
• Language: English
• Published: London Dove Medical Press Limited 01-01-2020; Dove Medical Press Ltd; Dove; Dove Medical Press
• Subjects: Analysis; Antibiotics; Chronic obstructive lung disease; Chronic obstructive pulmonary disease; Demographics; ecii; exacerbations; Generalized linear models; indacaterol/glycopyrronium; lung function; Medical research; Original Research; Patient outcomes; Patients; Pharmaceutical industry; Prognosis; pros; Questionnaires; United States; United Kingdom
• ISSN: 1178-2005; 1176-9106; 1178-2005
• DOI: 10.2147/COPD.S247966

Background: Chronic obstructive pulmonary disease (COPD) exacerbations are difficult outcomes to measure in clinical trials. It would be valuable to be able to predict which patients are likely to benefit in terms of exacerbation prevention based on their early response in lung function and symptoms. Methods: This was a post-hoc analysis from the 52-week, randomized, double-blind, double-dummy, non-inferiority FLAME trial. Early clinically important improvement (ECII) was defined as achievement of minimal clinically important difference in trough forced expiratory volume in 1 second ([FEV.sub.1]; [greater than or equal to]100 mL increase) and one patient-reported outcome (PRO): either St. George's Respiratory Questionnaire for COPD ([greater than or equal to]4-unit reduction; D1), or COPD assessment test ([greater than or equal to]2-point reduction; D2) at Week 4 or 12. Results: Approximately 18-20% of patients achieved ECII at Week 4 or 12 post-randomization according to any of the two definitions. The rate of subsequent exacerbations was lower in patients who achieved ECII at Week 4 (D1: ratio of rates [95% CI], 0.85 [0.74 to 0.98]; D2, 0.88 [0.77 to 1.00]) or at Week 12 (D1, 0.85 [0.74 to 0.98]; D2, 0.86 [0.75 to 1.00]) versus patients not achieving ECII. Patients who achieved ECII experienced longer time-to-first exacerbation between Week 4 or 12 to end of study. More patients achieved ECII with indacaterol/glycopyrronium versus salmeterol/fluticasone according to both definitions at Week 4 (D1, odds ratio [95% CI], 1.69 [1.40 to 2.04]; D2, 1.61 [1.34 to 1.93]), and 12 (D1, 2.01 [1.66 to 2.44]; D2, 1.80 [1.48 to 2.18]). Conclusion: ECII is a novel composite endpoint, based on clinically relevant improvement in lung function and PROs in the early phase of treatment intervention that may predict subsequent exacerbation risk and may be used in clinical trials. Keywords: exacerbations, ECII, indacaterol/glycopyrronium, lung function, PROs