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Unraveling Triple Therapy in Chronic Obstructive Pulmonary Disease

Wedzicha JA.

RDD Europe 2019. Volume 1, 2019: 1-6.

Abstract:

Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and health burden, and exacerbations are one of the most frequent causes of hospital admission. The last few years has seen the introduction of novel single inhalers mainly once-daily dual bronchodilators comprising long acting beta agonists (LABA) and antimuscarinic agents (LAMA), that are effective in reducing dyspnea and also play an important role in exacerbation prevention. The FLAME study showed that a dual bronchodilator is more effective than a LABA and inhaled corticosteroid (ICS) combination on exacerbation prevention in COPD patients with medium risk of developing exacerbations (one or more exacerbations/year). ICS are used for exacerbation prevention and to date have no other role in COPD management. 

Over the last 12 months, the first studies have been published of “closed” triple therapy (LABA/LAMA/ICS in a single inhaler) for exacerbation prevention in COPD. The TRIBUTE study compared triple therapy to LABA/LAMA, but the patients studied had mainly one exacerbation in the previous year and were similar in exacerbation risk to the FLAME trial cohort. The IMPACT study compared triple therapy to LABA/LAMA and LABA/ICS and showed benefits of triple over both dual combinations in a cohort of patients at greater risk of developing exacerbations. There is also emerging data on the role of blood eosinophils in predicting ICS response, but the origin of raised blood eosinophils in COPD is not understood. However, blood eosinophil levels above 300 cells/μL may indicate which patients with COPD and low risk of exacerbations may be withdrawn from triple therapy, as seen in the SUNSET withdrawal study of ICS.

COPD exacerbation frequencies may also change over time and it is important to understand how escalation and de-escalation of COPD therapy needs to be performed to optimize therapy and minimize adverse effects.