Are Long-Acting Beta-Agonists Safe to Add to Treatment Regimens for Asthma in Children?

Posted by • August 31st, 2016

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Janine is a 9-year-old girl who you’ve been seeing in your clinic for years. She struggles with asthma despite treatment with low-dose inhaled glucocorticoids. You wonder if any other medications can be added to her treatment regimen, and peruse the literature on long-acting beta-agonists (LABAs). The literature is mixed – it seems clear that LABAs, when used alone, have been associated with increased risk of asthma-related deaths. However, more recent studies have reported that LABAs may be safer when combined with low-dose inhaled glucocorticoids. Indeed, in the recent AUSTRI study, there was no increased risk of serious asthma-related events in adults and adolescents with moderate asthma who received LABA with glucocorticoids, compared with those receiving glucocorticoids alone. However, this study did not include patients of Janine’s age, and thus, the safety of combining LABAs with glucocorticoids in children remains unclear.

In this week’s issue of NEJM, Stempel et al. address this issue in the VESTRI trial — a randomized, double-blind, international 26-week trial involving 6208 asthmatic children (aged 4-11 years). The children were randomized to receive either the glucocorticoid fluticasone propionate with the LABA salmeterol or fluticasone-alone. For the primary endpoint of asthma-related events, fluticasone-salmeterol combination therapy was noninferior to fluticasone-alone, with similar risk of asthma-related events in the two groups. Additionally, the fluticasone-salmeterol combination therapy group had a nonsignificant 14% reduction in severe asthma exacerbations compared to the fluticasone-alone group.

In an accompanying editorial, Bush and Frey applaud this trial for its large sample size and low number of adverse events. However, they caution against immediately starting patients like Janine on combination glucocorticoid-LABA therapy, especially as a first-line treatment. Most asthmatic children, they argue, can still be well controlled on inhaled glucocorticoid therapy, and checking with the family about action plans, adequacy of medication delivery technique, and other steps to control asthma should be taken before adding LABAs to the treatment plan.

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