Study Reports Advair Safe for Use in Children With Asthma

According to recent trial results published in the New England Journal of Medicine, administration of Advair (fluticasone-salmeterol; GlaxoSmithKline) combination therapy for treatment of severe asthma among children demonstrated a similar safety profile to glucocorticoid monotherapy.

For patients with asthma, long-acting beta-agonists (LABAs) have been shown to increase the risk of severe asthma-related adverse events, including death among adults. In order to determine the safety of administering LABAs to children as a combination therapy with glucocorticoid, the researchers compared the safety of fluticasone-salmeterol to fluticasone alone.

“We are pleased that the study achieved its primary safety endpoint and has now been published in a key peer-reviewed journal as well as being presented at the forthcoming European Respiratory Society congress,” Kate Knobil, chief medical officer of pharmaceuticals at GlaxoSmithKline said in a press release. “These are important data, especially in an area where data are limited, such as in pediatric asthma.”  

The researchers randomly assigned children aged 4 to 11 years who required daily asthma medication and had a history of asthma exacerbations in the previous year to one of four study groups, two fluticasone-salmeterol groups and two fluticasone only groups. The children in the combination therapy groups received either a fixed-dose combination of fluticasone propionate at a dose of 100 μg plus salmeterol at a dose of 50 μg, a fixed-dose combination of fluticasone at a dose of 250 μg plus salmeterol at a dose of 50 μg. The children in the monotherapy group received either 100 μg or 250 μg of fluticasone alone

________________________________________________________________________________________________________________________________________________________________________

RELATED CONTENT
Novartis Asthma Pill Shows Promise in Small Trial
Pediatricians' Group Backs ACIP on Serogroup B Meningococcal Vaccines
________________________________________________________________________________________

The primary safety endpoint focused on the first serious asthma-related event, including death, endotracheal intubation, or hospitalization assessed in a time-to-event analysis. The main efficacy endpoint was the first severe asthma exacerbation that led to treatment with systemic glucocorticoids, also assessed in a time-to-event analysis.

Study results showed that combination therapy was associated with a risk of a serious asthma-related event that was similar to the risk with fluticasone alone. Of the 6208 patients, 27 patients in the fluticasone-salmeterol group and 21 in the fluticasone-alone group experienced a serious asthma-related event. The fluticasone-salmeterol hazard ratio was 1.28 (95% CI, 0.73-2.27) showing the noninferiority of the fluticasone-salmeterol combination (P = .006). Additionally, 265 patients (8.5%) in the fluticasone-salmeterol combination group and 309 (10%) in the fluticasone-alone group experienced severe asthma exacerbation (HR = 0.86; 95% CI, 0.73-1.01).

In an accompanying editorial, Andrew Bush, MD, of the Royal Brompton Hospital in London and Urs Frey, M, PhD, of the University Children’s Hospital Basel at the University of Basel in Switzerland, wrote that they found these findings reassuring.

“It is reassuring to see… a report of a large, well-conducted trial involving children that was mandated by the Food and Drug Administration (FDA) and that shows no excess of serious asthma events in children receiving a combination inhaler containing fluticasone propionate and salmeterol,” they wrote.

However, they also expressed safety concerns over the use of combination therapy as a first-line therapy in pediatric patients.

“There is no evidence for the use of a combined inhaler as first-line preventive therapy in children, and this fact needs to be emphasized because such use is increasingly creeping into practice,” Bush and Frey wrote. “However, for the unusual child with asthma who needs more than low-dose inhaled glucocorticoids to control the disease or who has persistent, objectively documented, variable airflow obstruction, the present trial provides reassuring evidence that combination inhalers containing a LABA and an inhaled glucocorticoid are safe.”

This study was funded by GlaxoSmithKline as part of the VESTRI trial. ---Julie Gould

Reference: