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

Antonio R Anzueto, Konstantinos Kostikas, Karen Mezzi, Steven Shen, Michael Larbig, Francesco Patalano, Robert Fogel, Donald Banerji, Jadwiga A Wedzicha, Antonio R Anzueto, Konstantinos Kostikas, Karen Mezzi, Steven Shen, Michael Larbig, Francesco Patalano, Robert Fogel, Donald Banerji, Jadwiga A Wedzicha

Abstract

Background: Chronic 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.

Methods: CID 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.

Results: IND/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.

Conclusions: IND/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 registration: Clinicaltrials.gov NCT01782326 .

Keywords: CID; COPD; Chronic obstructive pulmonary disease; Clinically important deterioration; FLAME; Indacaterol/glycopyrronium; LABA/LAMA; Salmeterol/fluticasone.

Conflict of interest statement

Ethics approval and consent to participate

The study complied with the Declaration of Helsinki and the International Conference on Harmonisation and Good Clinical Practice guidelines. The protocol was approved by the regulatory authority for each country (where applicable) and an independent ethics committee at each center. All patients provided written informed consent.

Consent for publication

Not applicable.

Competing interests

AA has received honoraria for consultant services and speaking from Novartis, AstraZeneca, Boehringer Ingelheim, Sunovion Pharma, and GlaxoSmithKline. JAW has received no honoraria for lectures, consultant services and/or advisory boards. She has received research grants from Novartis, AstraZeneca, Boehringer Ingelheim, Johnson and Johnson, Sunovion Pharma, GlaxoSmithKline. KK is an employee and shareholder at Novartis Pharma AG. KK has previously received honoraria for speeches and consulting services from AstraZeneca, Boehringer Ingelheim, Chiesi, ELPEN and Takeda, outside the submitted work. None of the authors received any compensation for the development of the manuscript.

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Figures

Fig. 1
Fig. 1
Study design. b.i.d., twice daily; IND/GLY, indacaterol/glycopyrronium; o.d., once daily; OL, open-label; SFC, salmeterol/fluticasone; TIO, tiotropium
Fig. 2
Fig. 2
Kaplan–Meier curves and Cox proportional hazard-model for time-to CID during 52 weeks of treatment. b.i.d., twice daily; CID, clinically important deterioration; IND/GLY, indacaterol/glycopyrronium; o.d., once daily; SFC, salmeterol/fluticasone
Fig. 3
Fig. 3
Hazard ratios and respective 95% CI for time-to CID by subgroup during 52 weeks of treatment. b.i.d., twice daily; CI, confidence interval; CID, clinically important deterioration; COPD, chronic obstructive pulmonary disease; HR, hazard ratio; IND/GLY, indacaterol/glycopyrronium 110/50 μg o.d.; o.d., once daily; SFC, salmeterol/fluticasone 50/500 μg b.i.d

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