Indacaterol/glycopyrronium versus salmeterol/fluticasone in the prevention of clinically important deterioration in COPD: results from the FLAME study

Abstract

BackgroundChronic obstructive pulmonary disease (COPD) is a progressive disease and a composite endpoint could be an indicator of treatment effect on disease worsening. This post-hoc analysis assessed whether indacaterol/glycopyrronium (IND/GLY) 110/50 μg once daily reduced the risk of clinically important deterioration (CID) versus salmeterol/fluticasone (SFC) 50/500 μg twice daily in moderate-to-very severe COPD patients from the FLAME study.MethodsCID was defined as ≥100 mL decrease in forced expiratory volume in 1 s (FEV1) or ≥ 4-unit increase in St. George’s Respiratory Questionnaire (SGRQ) total score or a moderate-to-severe COPD exacerbation. Changes from baseline in the rate of moderate and severe exacerbations, time to first moderate-to-severe exacerbation, and change from baseline in the SGRQ score, measured after Week 12 up to Week 52, were assessed by presence of early CID (CID+) or absence of CID (CID−) at Week 12.ResultsIND/GLY significantly delayed the time to CID (hazard ratio [HR] (95% confidence interval [CI]), 0.72 [0.67–0.78]; P < 0.0001), and reduced the incidences of CID versus SFC. Additionally, IND/GLY delayed the time to CID in all patient subgroups. After 12 weeks until 52 weeks, CID+ patients had a significantly higher rate of moderate-to-severe exacerbations versus CID− patients (P < 0.0001); moreover, CID+ patients experienced moderate-to-severe exacerbations significantly earlier versus CID− patients (P < 0.0001). CID+ patients had a comparable change in the SGRQ total score versus CID− patients.ConclusionsIND/GLY reduced the risk of CID versus SFC. CID had a significant impact on long-term exacerbation outcomes in patients with moderate-to-very severe COPD and a history of ≥1 exacerbations in the previous year.Trial registrationClinicaltrials.gov NCT01782326.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0830-z) contains supplementary material, which is available to authorized users.

Current evidence for COPD management with dual long-acting muscarinic antagonist/long-acting β2-agonist bronchodilators

“…At the time of writing, there is limited evidence on the risk of a composite CID in studies comparing LAMA/LABA and ICS/ LABA. A post hoc analysis of data from the FLAME study showed a 28% reduction in the risk of a first short-term deterioration with LAMA/LABA compared with ICS/LABA (hazard ratio: 0.72; 95% CI: 0.67, 0.78; P < 0.001) [53]. The composite CID endpoint includes the occurrence of a moderate/severe exacerbation, and so the reduction in CID risk should be interpreted with caution due to the mixed evidence regarding the relative effects of LAMA/LABA and LABA/ICS on exacerbation risk.…”

Adherence of North-African Pulmonologists to the 2017-Global Initiative for Chronic Obstructive Lung Disease (GOLD) Pharmacological Treatment Guidelines (PTGs) of Stable Chronic Obstructive Pulmonary Disease (COPD)

“…Local spirometric norms were used [31]. COPD exacerbation was defined as an acute event characterized by a deterioration of the patient's respiratory symptoms that are beyond the normal day-to-day variations and which leads to treatment modification [32].…”

Reduced risk of clinically important deteriorations by ICS in COPD is eosinophil dependent: a pooled post-hoc analysis

“…In our study we found that the individual CID components contributed substantially to the total CID rate, with the effects of BUD/FORM versus FORM on CID generally reflected by the individual components. A post-hoc analysis of the FLAME study [16], in which the effect of indacaterol/glycopyrronium versus salmeterol/ fluticasone on CID was evaluated in patients with an exacerbation history, showed a greater effect of the dual bronchodilator on CID prevention. The largest effect was seen on FEV 1 deteriorations, consistent with other bronchodilator studies [1,[3][4][5][6].…”