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Tuesday, July 5, 2011

What do we really need to appraise the safety of combined long-acting ß2 agonists and inhaled corticosteroids in asthma?

The safety of LABAs has been questioned since their introduction in the early 1990s, and we do not have the answer yet. In an attempt to improve the safety of these drugs, the U.S. Food and Drug Administration (FDA) last year issued a requirement that labels for LABA-containing products should be changed with respect to asthma treatment. These changes state that LABAs are contraindicated without the concomitant use of an asthma controller medication, such as an inhaled corticosteroid. Furthermore, the revised labels recommend that LABAs are only to be used when they are necessary to achieve and maintain asthma control. While LABAs used by themselves increase the risk of serious adverse outcomes, it is still unclear whether there are similar risks when LABAs are added to inhaled corticosteroids. More studies are still needed to fully understand this key issue.

In a Perspective published in the New England Journal of Medicine (N Engl J Med 2011;364:2473-2475), Badrul Chowdhury and colleagues, from the FDA, provide some insights into the future studies that need to be carried out. This question cannot be answered through reanalysis of existing data, analyses of spontaneous reports of adverse events, or epidemiologic studies using existing databases; controlled clinical trials are necessary.

This April, the FDA issued a requirement that manufacturers of all LABAs marketed for asthma in the U.S. must conduct 5 controlled clinical trials to compare the safety of treatment with LABAs plus inhaled corticosteroids to treatment with inhaled corticosteroids alone. Even children as young as 4 will be enrolled in one of the trials. The 6-month trials will be multinational, randomized, and double-blind. The plan is to “mimic a real-world scenario,” and the FDA believes that “these clinical trials will provide data in a timely fashion that will clarify the safety risk associated with LABAs when used concurrently with inhaled corticosteroids and will inform the safe use of these medications for the treatment of asthma.”

What are your expectations for these trials? Are they going to change your practice?