Once-daily indacaterol/glycopyrronium reduces the rate and risk of moderate or severe exacerbations compared with twice-daily salmeterol/fluticasone in a subset of gold froup D COPD patients with a history of >= 2 exacerbations or 1 hospitalization: the FLAME study

Introduction:

One of the major goals of COPD treatment is to reduce the severity and frequency of exacerbations.¹ Patients categorized into Global Initiative for Chronic Obstructive Lung Disease (GOLD) Group D have severe-to-very severe airflow limitation, and/or exacerbations, and significant symptoms.¹ LABA/ICS or/and a LAMA are recommended as the first choice treatment for Group D patients.¹ FLAME was the first study that demonstrated the superiority of indacaterol/glycopyrronium (IND/GLY), a LABA/LAMA combination, in reducing exacerbations, improving lung function, and health status versus salmeterol/fluticasone (SAL/FLU), a LABA/ICS combination, in moderate-to-very severe COPD patients with a history of exacerbations.² Here, we present a subset analysis of GOLD Group D patients who had a history of ≥2 exacerbations or 1 hospitalization for exacerbation. Effects of IND/GLY vs. SAL/FLU on the rate and risk of moderate or severe exacerbations were compared.

Methods:

FLAME was a 52-week, randomized, double-blind, double-dummy, parallel-group study. 3362 patients with moderate-to-very severe COPD, post-bronchodilator FEV₁ ≥25% to < 60% of the predicted normal, and a history of ≥1 exacerbation in the previous year were randomized (1:1) to receive either IND/GLY (110/50 µg) once daily or SAL/FLU (50/500 µg) twice daily. The rate and time to moderate or severe exacerbations were analyzed in the subset of GOLD Group D patients with a history of ≥2 exacerbations or 1 hospitalization.

Results:

IND/GLY demonstrated superior efficacy over SAL/FLU in reducing the rate of moderate or severe exacerbations (rate ratio, 0.86; Table). IND/GLY delayed the time-to-first moderate or severe exacerbation compared with SAL/FLU (median days: 291 vs. 215; Table). The patients treated with IND/GLY had a 19% lower risk of a moderate or severe exacerbation compared with SAL/FLU.

Tab. 1:

Effect of IND/GLY versus SAL/FLU on moderate or severe exacerbations in the subset of GOLD Group D patients with a history of ≥2 exacerbations or 1 hospitalization for exacerbation

Annualized rate
	Indacaterol/glycopyrronium (n = 531)	Salmeterol/fluticasone (n = 503)
Rate (95% CI)	1.26 (1.06 to 1.51)	1.47 (1.24 to 1.75)
Rate ratio* (95% CI)	0.86 (0.74 to 1.00)
P value	0.05
Time-to-first exacerbation
	Indacaterol/glycopyrronium (n = 536)	Salmeterol/fluticasone (n = 511)
Patients with event, n (%)	281 (52.4)	299 (58.5)
Patients without event, n (%)	255 (47.6)	212 (41.5)
Time at risk (days), median (range)	247.5 (1 to 419)	181 (2 to 386)
Time-to-event (days), median (95% CI)	291 (254 to 352)	215 (175 to 261)
Hazard ratio* (95% CI)	0.81 (0.69 to 0.96)
P value	0.013
* indacaterol/glycopyrronium versus salmeterol/fluticasone

Conclusions:

IND/GLY was superior to SAL/FLU in reducing the rate and risk of moderate or severe exacerbations in a subset of GOLD Group D patients who had a history of ≥2 exacerbations or 1 hospitalization for exacerbation. Our results confirm the use of IND/GLY as a preferred treatment option for COPD patients at high risk of exacerbations.

References:

[1] GOLD 2016. Available from: www.goldcopd.org

[2] Wedzicha JA et al. N Engl J Med. 2016;374(23):2222 – 2234