A 'Triple' for COPD?

Nicholas Gross, MD, PhD


October 10, 2017

We cannot cure chronic obstructive pulmonary disease (COPD). However, because advanced COPD causes much disability, acute exacerbations, and mortality and is associated with high cost, we strive to limit those aspects of the condition. To that end, we use all of the pharmaceuticals at our disposal within the limits of avoiding toxic effects.

It has been shown that long-acting beta-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) separately provide symptom relief and reduce acute exacerbations. The addition of an inhaled corticosteroid (ICS) to a LABA provides further relief. These agents bring about benefits in different ways and work at different receptors. It is logical, then, to combine them in our therapies. Thus, fixed combinations of pairs have become standard.

In practice, many patients with severe or very severe COPD already use all three modalities. It is appropriate, therefore, to complete the process and develop a fixed ICS/LABA/LAMA combination—which several pharmaceutical companies are working to construct.

One such company, GlaxoSmithKline, conducted a phase 3 study called FULFIL,[1] which evaluated a fixed combination of fluticasone furoate (the ICS), umeclidinium (the LAMA), and vilanterol (the LABA) in a once-daily formulation. The double-blind study, which enrolled patients with advanced COPD, compared the triple therapy with an approved twice-daily ICS/LABA (budesonide/formoterol) preparation.

In the 24-week trial, the co-primary outcomes were lung function (FEV1) and health status (scores on the St George's Respiratory Questionnaire). The trial found that triple therapy exceeded the lung function and health status by amounts that were statistically and clinically meaningful compared with ICS/LABA.

The study also compared the associated costs of each treatment.[2] Over 52 weeks, unscheduled healthcare requirements were fewer in patients receiving triple therapy than those receiving double therapy. Nondrug costs were lower in patients receiving triple therapy. Both studies were conducted and reported in UK reference costs.

Potential advantages of triple over double therapy include greater lung function and quality of life, with clinically significant differences. Presumably owing to its clinical benefits, triple therapy may also offer cost benefits, although the financial benefit was not very great and results of the FULFIL trial cannot be extended to the health system in the United States.

The ICS/LABA/LAMA fixed combination has the benefit that it combines all the therapeutic advantages of a COPD treatment in a single device which, in this case, needs to be administered only once daily. Together with the convenience of a single daily administration, it will not be possible for patients to skip doses or individual medications. It should be used only in patients with severe or very severe COPD. Correspondingly, there is concern that it will be used inappropriately in patients with less than severe COPD.

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