Is Health Status and Symptom Burden at Baseline Related to the Risk of Exacerbation in COPD?

Introduction

Chronic obstructive pulmonary disease (COPD) is a heterogenous disease and characterized by worsening of symptoms and persistent airflow limitation. The risk of exacerbation has been associated with symptom burden in terms of health status impairment, blood eosinophil levels, smoking status, bronchitis and dyspnea. Patients may respond differently to different therapies depending on the baseline symptoms.  

Aim

This study assessed the impact of baseline health status, symptom severity, key clinical characteristics, including dyspnea and bronchitis, eosinophil levels and smoking status on the risk of exacerbations and response to treatment in COPD patients.

Methods

Study Design

• Post hoc analysis from the landmark FLAME study

Treatment Strategy

• Patients included in FLAME study were aged ≥40 years, with symptomatic COPD
• Post-bronchodilator forced expiratory volume in 1 s (FEV₁) of ≥25 to < 60% of the predicted value, and a post-bronchodilator FEV₁/forced vital capacity < 0.70.
• Randomized to receive either indacaterol/glycopyrronium (IND/GLY) 110/50 ?g once daily or salmeterol/fluticasone (SFC) 50/500 ?g twice daily for 52 weeks
• Patients from the full analysis set of the FLAME study were divided into groups based on baseline symptoms, presence of disease, clinical characteristics and smoking status

Endpoints

• Health status measured by St. George’s Respiratory Questionnaire (SGRQ) score (higher ≥46.6 and lower < 46.6)
• COPD Assessment Test (CAT) score (higher ≥17 and lower < 17)
• Dyspnoea and bronchitis evaluated via an electronic diary (eDiary)
• Differential response to once-daily indacaterol/glycopyrronium (IND/GLY) 110/50 ?g versus twice-daily salmeterol/fluticasone (SFC) 50/500 ?g

Results

• The overall population of 3354 patients with a mean age of 65 years was analyzed.
• The risk of exacerbations was lower in patients with less severe health impairment demonstrated by lower baseline CAT (< 17) and SGRQ-C (< 46.6) scores (rate ratio [RR] for CAT: 0.85; p = 0.011 and SGRQ-C: 0.88; p = 0.037), regardless of treatment received
• Patients with lower baseline dyspnea had a lower annualized exacerbation rate than those with higher dyspnea (RR, 0.79; p < 0.001)
• IND/GLY group demonstrated greater reduction in exacerbation frequency as compared to SFC group in patients with lower dyspnea scores
• However, the efficacy of both IND/GLY and SFC was similar in patients with higher dyspnea scores
• Patients with bronchitis experienced a lower rate of exacerbations (RR, 0.77; p < 0.002), irrespective of treatment received
• The annualized exacerbation rate was lower in patients with bronchitis treated with IND/GLY
• The rate of exacerbations was not affected by the baseline blood eosinophil levels (RR, 1.03; p = 0.624) and total symptom burden
• The efficacy of IND/GLY was better than SFC in patients with lower blood eosinophil levels (< 300 cells/?L)
• However, in patients with higher blood eosinophil levels (≥300 cells/?L), the efficacy of both the treatments was comparable
• Baseline smoking status did not have any impact on the rate of exacerbation (RR, 1.03; p = 0.603)
• However, in both current and ex-smokers, IND/GLY demonstrated better efficacy in terms of reducing the rates of exacerbations

Conclusion

• The results of the FLAME study showed that COPD patients with more severe health impairment and greater symptom burden at baseline experienced more exacerbations.
• The efficacy of indacaterol/glycopyrronium in reducing exacerbations was better as compared to salmeterol/fluticasone.
• Patients with higher symptom burden at baseline in addition to history of previous exacerbations should be included in future studies on novel exacerbation therapies.

Respir Res 21, 93 (2020). Doi:10.1186/s12931-020-01354-8.