Results of the FLAME study spark new discussion about the treatment of COPD

03.06.2016 10:31

In a head-to-head comparison, glycopyrronium/indacaterol (e.g. "Ulunar") was the only LAMA/LABA combination to date to show superiority over ICS/LABA (salmeterol/fluticasone) in reducing exacerbations. In the FLAME trial data published in the New England Journal of Medicine, the primary endpoint of non-inferiority was met and superiority was even demonstrated. Glycopyrronium/indacaterol - a drug combination of the long-acting anticholinergic glycopyrronium (LAMA) and the long-acting beta-2 sympathomimetic indacaterol (LABA) - was more effective than the combination of salmeterol and fluticasone in preventing exacerbations in patients with at least one exacerbation in the previous year .

The Flame study was a double-blind, double-dummy, active-controlled, non-inferiority study conducted for 52 weeks. The study involved 3,362 patients with moderate to very severe COPD. All had at least one exacerbation in the previous year that required treatment with an antibiotic and/or systemic corticosteroid. Participants were randomized 1:1 to receive either 50 μg glycopyrronium/110 μg indacaterol or 50 μg salmeterol/500 μg fluticasone for the duration of the study. The primary endpoint of the study was non-inferiority of glycopyrronium/indacaterol in the rate of exacerbations (mild, moderate, severe).

Superiority over ICS/LABA The results of the FLAME study, presented for the first time in May at the Annual Meeting of American Thoracic Society (ATS), demonstrated the superiority of glycopyrronium/indacaterol over the ICS/LABA combination salmeterol/fluticasone in reducing the COPD exacerbation rate.

The most important results of the FLAME study:

• All subpopulations benefited from a reduction in the exacerbation rate (mild, moderate, severe) with glycopyrronium/indacaterol compared to salmeterol/fluticasone.
• The rate of moderate or severe exacerbations was significantly reduced by 17 % (p<0.001).
• The time to first moderate or severe exacerbation was significantly increased by 22 % (p<0.001).
• The rate of all exacerbations was significantly reduced by 11 % (p=0.003) ; At the same time, the time to the first exacerbation increased significantly by 16 % (p<0.001).

Furthermore, from week 12 to week 52, the participants' quality of life improved significantly with glycopyrronium/indacaterol compared to salmeterol/fluticasone. Lung function was also better with glycopyrronium/indacaterol at week 52 than at baseline. However, the ICS/LABA combination resulted in a loss of lung function compared to baseline. The tolerability profiles of both treatments were comparable. However, the risk of pneumonia was significantly higher with salmeterol/fluticasone than with glycopyrronium/indacaterol (3.2 % versus 4.8%).

The effect of glycopyrronium/indacaterol on exacerbations was independent of baseline eosinophil concentration. Glycopyrronium/indacaterol significantly reduced the rate of moderate or severe exacerbations by 20 % in study participants with <2 % blood eosinophils at baseline and by 15 % in participants with ≥2 % blood eosinophil concentration at baseline compared to sameterol/fluticasone.

Goal: Reduction of exacerbations

Preventing new exacerbations is considered the primary goal in the treatment of COPD. The associated irreversible loss of lung function worsens the prognosis and has a significant impact on the quality of life and mortality of patients. The treatment of patients with frequent exacerbations with bronchodilator therapy in conjunction with an inhaled corticosteroid (ICS), which was previously recommended in the Gold guidelines, is once again under discussion due to the results of the FLAME study.