LABAs + ICS No Better Than ICS Alone for Asthma Attacks

Joe Barber Jr, PhD

August 27, 2012

August 27, 2012 — Long-acting β-agonists (LABAs) in combination with inhaled corticosteroids (ICS) do not appear to reduce the risk for asthma exacerbations compared with higher doses of ICS alone, according to the findings of a systematic review. However, the combination treatment does appear to improve pulmonary function and decrease the need for rescue medication.

Jose A. Castro-Rodriquez, MD, PhD, from Pontificia Universidad Cat&ocute;lica de Chile in Santiago, and Gustavo J. Rodrigo, MD, from Hospital Central de las Fuerzas Armadas in Montevideo, Uruguay, presented their findings in an article published online August 27 in Pediatrics.

The authors note that studies are increasingly investigating asthma in pediatric populations. "In recent years, more studies enrolling children exclusively have appeared in the literature," the authors write. "Therefore, it is important to know which option (increased doses of ICS or the addition of LABA) is better for step 3 of the guidelines for children when low doses of ICS do not control their asthma."

For this systematic review, the authors searched Medline, EMBASE, Cochrane, and manufacturer's databases for randomized studies that compared the combination of LABAs and ICS with higher doses of ICS alone in children aged 4 to 18 years for at least 4 weeks. They identified 9 studies, including a total of 1641 children. The authors excluded nonrandomized, non-placebo-controlled, retrospective, and post hoc studies, as well as studies that included nonasthmatics.

Overall, the combination of LABAs and ICS did not significantly reduce the number of patients with asthma exacerbations requiring systemic corticosteroids compared with higher doses of ICS alone (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.48 - 1.22; P = .25).

In a subgroup analysis, the researchers found that the combination of LABAs and ICS significantly reduced the risk for exacerbations compared with higher than a double dose of ICS alone, (OR, 0.48; 95% CI, 0.28 - 0.82; P = .007; I 2, 0%).

Additional subgroup analysis revealed that the combination of LABAs and ICS improved the morning (weighted mean difference [WMD], 8.74; 95% CI, 4.87 - 12.51; I 2, 0%) and evening (WMD, 4.41; 95% CI, 1.77 - 7.05; I 2, 0%) peak expiratory fraction from baseline compared with higher doses of ICS. The combination treatment was also associated with a modest but significant reduction in the use of rescue medication (−0.11 puffs/day; 95% CI, −0.20 to −0.01 puffs/day). In addition, among 3 trials that evaluated more than a double dose of ICS, short-term growth was significantly greater in children who received the combination therapy (WMD, 0.66 cm/year; 95% CI, 0.05 - 1.25 cm/year).

No differences in the incidence of adverse events (54.6% vs 55.6%), including severe adverse events (2.0% vs 2.6%), were observed between the 2 types of treatment. The investigators found no evidence of publication bias (Egger's test, 0.35; 95% CI, −0.4 to 0.74) or significant heterogeneity among studies (I 2, 16%).

The limitations of the analysis included the small number of studies and the inability to perform subgroup analysis of the main outcome to compare different age groups.

Leslie Hendeles, PharmD, from the University of Florida in Gainesville, noted that these findings oppose the suggested lack of safety of these agents. "These findings counter the [US Food and Drug Administration (FDA)] concern about the safety of LABAs in children," Dr. Hendeles told Medscape Medical News by email. "We need to see the FDA-mandated studies, which will be conducted in thousands of children."

Dr. Castro-Rodriquez received funding to attend scientific meetings from AstraZeneca, GlaxoSmithKline, Merck Sharp & Dohme, and Novartis. Dr. Rodrigo received funding to attend scientific meetings from scientific meeting sponsorship from AstraZeneca, Boehringer Ingelheim, Dr Esteve SA, GlaxoSmithKline, and Merck Sharp & Dohme. Dr. Heneles served as an expert witness in defense of Teva Pharmaceutical, which makes a product containing an ICS, in a patent dispute.

Pediatrics. Published online August 27, 2012. Abstract

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