Impact of baseline symptoms and health status on COPD exacerbations in the FLAME study

Alexander J Mackay, Konstantinos Kostikas, Nicolas Roche, Stefan-Marian Frent, Petter Olsson, Pascal Pfister, Pritam Gupta, Francesco Patalano, Donald Banerji, Jadwiga A Wedzicha, Alexander J Mackay, Konstantinos Kostikas, Nicolas Roche, Stefan-Marian Frent, Petter Olsson, Pascal Pfister, Pritam Gupta, Francesco Patalano, Donald Banerji, Jadwiga A Wedzicha

Abstract

Background: COPD is a heterogeneous disease and patients may respond differently to therapies depending on baseline symptom burden.

Methods: This post-hoc analysis from the 52-week FLAME study investigated the impact of baseline symptom burden in terms of health status, dyspnoea, bronchitis status, eosinophil levels and smoking status on the subsequent risk of moderate or severe exacerbations. Health status was measured by St. George's Respiratory Questionnaire (SGRQ) score (higher ≥46.6 and lower < 46.6) and COPD Assessment Test (CAT) score (higher ≥17 and lower < 17); dyspnoea and bronchitis were assessed via an electronic diary (eDiary). Differential response to once-daily indacaterol/glycopyrronium (IND/GLY) 110/50 μg versus twice-daily salmeterol/fluticasone (SFC) 50/500 μg was assessed.

Results: Data from 3354 patients was analysed. The risk of exacerbations was lower in patients who had less severe health impairment (rate ratio [RR] [95% CI]): SGRQ-C, (0.88 [0.78, 0.99]); CAT, 0.85 [0.75, 0.96]) and lower dyspnoea (0.79 [0.69, 0.90]) at baseline versus those with more severe health impairment and higher dyspnoea, respectively. Compared with SFC, IND/GLY led to better prevention of moderate-to-severe exacerbations in the majority of groups studied.

Conclusion: Patients with more severe health status impairment and greater symptom burden at baseline subsequently experienced more exacerbations in the FLAME study. IND/GLY was overall more effective in preventing exacerbations versus SFC, regardless of baseline symptom burden. Our results suggest that future studies on novel exacerbation therapies should consider targeting patients with higher symptom burden at baseline.

Clinical trial identifier: NCT01782326.

Keywords: Bronchitis; COPD burden; Dyspnoea; Health status; Indacaterol/glycopyrronium.

Conflict of interest statement

AJM and SMF were ERS fellows with Novartis Pharma AG during this work. AJM is now an employee of AstraZeneca. KK, PP and FP are employees and shareholders of Novartis Pharma AG, and DB is employees and shareholders of Novartis Pharmaceutical Corporation. PG is an employee of Novartis Healthcare Pvt. Ltd. PO is an employee of Novartis AB and shareholder of Novartis Pharma AG. NR reports grants from Boehringer Ingelheim, Pfizer and Novartis, and personal fees from Boehringer Ingelheim, Novartis, Teva, GSK, AstraZeneca, Chiesi, Mundipharma, Pfizer, Sanofi, Sandoz, 3 M, Zambon. JAW reports grants from GSK, Johnson and Johnson, Novartis, Boehringer Ingelheim, AstraZeneca and Chiesi, outside the submitted work.

Figures

Fig. 1
Fig. 1
Annualised rate of COPD exacerbations by baseline. (a) CAT and (b) SGRQ-C total scores. n, number of patients assessed in this analysis. CAT, COPD Assessment Test; CI, confidence interval; IND/GLY, indacaterol/glycopyrronium 110/50 μg once daily; SFC, salmeterol/fluticasone 50/500 μg twice daily; SGRQ-C, St. George’s Respiratory Questionnaire for COPD
Fig. 2
Fig. 2
Annualised rate of COPD exacerbations by baseline dyspnoea level measured via eDiary. n, number of patients assessed in this analysis. Dyspnoea was measured via eDiary based on median split of daily highest dyspnoea scores averaged over the run-in period. CI, confidence interval; COPD, chronic obstructive pulmonary disease; eDiary, electronic diary; IND/GLY, indacaterol/glycopyrronium 110/50 μg once daily; SFC, salmeterol/fluticasone 50/500 μg twice daily
Fig. 3
Fig. 3
Annualised rate of COPD exacerbations by baseline bronchitis status measured via eDiary. n, number of patients assessed in this analysis. Bronchitis was evaluated based on patients’ response to a specific question in the eDiary. Bronchitis and non-bronchitis patients were defined as those with daily highest sputum volume score of ≥1 (bronchitis) or 

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