What Bronchodilator Options Do We Have for COPD?

Chronic obstructive pulmonary disease (COPD) is common and can be highly symptomatic. Other than smoking cessation, we have no therapies that have been clearly shown to improve survival. Several treatments improve symptoms, however; these include bronchodilators with or without corticosteroids.

Progress has occurred rapidly since the 1990s, when two or three relatively short-acting agents were the only available treatments. We now have several long-acting, highly effective, and safe therapies, including combinations that provide symptom relief at little cost of increased adverse effects. Several 12- and 24-hour adrenergic agents and several long-acting antimuscarinic agents are now available, both singly and in fixed combinations. Some long-acting agents include an inhaled corticosteroid.

More of these agents and combinations are appearing almost monthly, giving rise to the following questions: Which agents are available? Which ones should be used for which patients? Are fixed combinations better than monotherapies? And what are the safety concerns?

A recent comprehensive review provides some answers.^[1] The investigators analyzed the results of 18 trials that compared fixed combinations of a long-acting beta-agonist/long-acting muscarinic antagonist (LABA/LAMA) with LAMA monotherapy. The LABAs included indacaterol, vilanterol, formoterol, salmeterol, or olodaterol; the LAMAs included glycopyrronium, umeclidinium, tiotropium, or aclidinium. Fluticasone was the inhaled corticosteroid (ICS) when a corticosteroid was a component.

The FEV₁ as measured after 12-52 weeks was significantly greater with the LABA/LAMA combination than with LAMA monotherapy. Similarly, the LABA/LAMA combination yielded greater improvements in lung function than a LABA/ICS combination. In general, the improvements seen with fixed LABA/LAMA combinations were of meaningful magnitude, with the exception being those combinations that included aclidinium.

Other important outcomes, such as less need to take reliever medications for breakthrough symptoms and frequency of acute exacerbations, were significantly better with combination bronchodilators. In addition, the adverse event rate was low in all treatment arms and did not differ between treatments.

Viewpoint

The guidelines for the management of COPD, the GOLD Guidelines,^[2] recommend that initial symptoms of COPD be treated with short-acting bronchodilators (SABAs) on an as-needed basis, moving to long-acting agents on a regular basis if symptoms are not adequately managed with a SABA. Either a LABA or a LAMA could be introduced on a 12- or 24-hour schedule. If symptoms deteriorate over time, as is common, a fixed combination, such as a LABA/LAMA, is appropriate.

As one might expect, two bronchodilators that relax airways through different and separate receptors result in more bronchodilation than one. Before LABA/LAMAs became widely available, the combination would have most likely been a LABA/ICS fixed combination, but we now recognize that unless the patient has a component of asthma or is having acute exacerbations of COPD, an ICS is not appropriate and carries a risk for pneumonia.

If symptoms are still not adequately controlled with a LABA/LAMA fixed combination, one may consider adding an ICS to the LAMA/LABA prescription by adding an ICS to a LABA/LAMA combination or by prescribing a fixed combination of a LABA/ICS plus a LAMA monotherapy. No fixed LABA/LAMA/ICS triple combination is available at present, but several are in clinical trials.

Among the various long-term monotherapies and fixed combinations, there is little to choose; with very few exceptions, all the bronchodilator molecules mentioned above are effective and relatively safe. The 12-hour or 24-hour duration of action can be an issue, and the patient may have a preference.

Abstract

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