Does Triple Therapy Benefit Patients With COPD?
Information sourced from NEJM Journal Watch:
Does Triple Therapy Benefit Patients with Chronic Obstructive Pulmonary Disease?
A randomized trial shows that adding an inhaled corticosteroid to a dual long-acting bronchodilator regimen limits COPD exacerbations.
Stepwise treatment for patients with chronic obstructive pulmonary disease (COPD), as recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD), consists of either a long-acting antimuscarinic antagonist (LAMA) or long-acting β-agonist (LABA) as the initial agent, followed by dual LAMA/LABA therapy, and, lastly, triple therapy with a LAMA, a LABA, and an inhaled corticosteroid (ICS; NEJM JW Gen Med Jun 15 2017 and Am J Respir Crit Care Med 2017; 195:557). Triple therapy is used widely, but its effectiveness compared with dual therapy has not been studied.
In an industry-funded, international multicenter trial, 1532 symptomatic COPD patients with forced expiratory volume in 1 second (FEV1) <50% of predicted and exacerbations in the past year were randomized to either triple therapy (twice-daily inhalations of beclomethasone, formoterol, and glycopyrrolate) or dual therapy (once-daily inhalation of indacaterol plus glycopyrrolate). During 1 year of treatment, patients in the triple-therapy group experienced significantly fewer moderate-to-severe exacerbations than did patients in the dual-therapy group (0.5 vs. 0.6 per patient annually; number needed to treat, 11). In subgroup analyses, benefit was most pronounced in patients with eosinophilia greater than 2% and in those with chronic bronchitis versus emphysema. Side effects were similar in both groups with no excess pneumonia cases. (However, another recent study showed a modest excess risk for fractures in COPD patients who receive long-term ICS; NEJM JW Gen Med Mar 15 2018 and Chest 2018; 153:321.)
This study affirms the current GOLD stepwise approach of reserving triple therapy for patients whose COPD is not controlled by LAMA/LABA dual therapy. Although the effect is modest, patients with eosinophilia, or chronic bronchitis or asthma/COPD overlap, seem to benefit most from adding an ICS, whereas it is probably less effective for those with noneosinophilic inflammation or emphysema.
David J. Amrol, MD reviewing Papi A et al. Lancet 2018 Feb 8.
Papi A et al. Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): A double-blind, parallel group, randomised controlled trial. Lancet 2018 Feb 8; [e-pub].
Agusti A. Filling the gaps in COPD: The TRIBUTE study. Lancet 2018 Feb 8; [e-pub].
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