Asthma Patients Treated Safely with Salmeterol-Fluticasone Combo

May 9, 2016

An FDA-mandated study finds use of LABA plus ICS in a single inhaler noninferior to ICS alone with regard to serious asthma outcomes.

[[{"type":"media","view_mode":"media_crop","fid":"48432","attributes":{"alt":"","class":"media-image media-image-right","height":"214","id":"media_crop_767568220606","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"5773","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"float: right;","title":"©sumroeng chinnapan/Shutterstock.com ","typeof":"foaf:Image","width":"357"}}]]Asthma patients who have not had life-threatening episodes and adhere to their drug regimen can safely use salmeterol together with fluticasone in a single inhaler, according to a new study.

Previously, studies had shown that patients taking the long-acting beta-agonist (LABA) salmeterol had an increased risk of severe asthma-related adverse events. The FDA mandated that the manufacturers of LABAs conduct randomized, double-blind, controlled clinical trials comparing the combination of these drugs with inhaled glucocorticoids in a single inhaler with inhaled glucocorticoids alone, using a composite of serious asthma outcomes (asthma-related death, intubation, or hospitalization) as the primary end point.

In this multicenter, randomized, double-blind trial, 11,679 adolescent and adult patients age 12 years and older with persistent asthma were assigned to receive either fluticasone with salmeterol or fluticasone alone for 26 weeks. All the patients had a history of a severe asthma exacerbation in the year before randomization, but not during the previous month. Patients were excluded from the trial if they had a history of life-threatening or unstable asthma.

The authors published their results in the March 6, 2016 issue of NewEngland Journal of Medicine.

The Glaxo Smith Kline-led study found 67 patients had 74 serious asthma-related events, with 36 events in 34 patients in the fluticasone–salmeterol group and 38 events in 33 patients in the fluticasone-only group, demonstrating non-inferiority was achieved.

There were no asthma-related deaths. Two patients in the fluticasone-only group underwent asthma-related intubation. The risk of a severe asthma exacerbation was 21% lower in the fluticasone–salmeterol group than in the fluticasone-only group, with at least one severe asthma exacerbation occurring in 480 of 5834 patients (8%) in the fluticasone–salmeterol group, as compared with 597 of 5845 patients (10%) in the fluticasone-only group.

The authors concluded that “patients who received salmeterol in a fixed-dose combination with fluticasone did not have a significantly higher risk of serious asthma-related events than did those who received fluticasone alone. Patients receiving fluticasone–salmeterol had fewer severe asthma exacerbations than did those in the fluticasone-only group.”

In an editorial in the same issue, Fernando D. Martinez, MD of the Arizona Respiratory Center, University of Arizona, Tucson, AZ, stated: “Most patients with asthma, and especially those without serious episodes, can reach high levels of symptom control and avoid frequent exacerbations by simply using their inhalers every day.”

However, Martinez noted that the study’s conclusion may not apply to patients who have the most severe and unstable disease “since these are the patients for whom all guidelines still recommend the use of LABAs combined with inhaled glucocorticoids as first-line treatment. For these patients, the safe clinical approach is to maintain the same precautions in using fluticasone–salmeterol that have been recommended until now for all patients with asthma.”

He also called for further exploration for the presence of rare variants in genes associated with the response to beta-agonists, which may increase the risk of severe exacerbations when these drug combinations are administered to patients with the most severe asthma.

 

Source: Stempel, DA, Raphiou, IH, Kral, Km, et al. Serious asthma events with fluticasone plus salmeterol versus fluticasone alone. New Engl J Med. March 6, 2016DOI: 10.1056/NEJMoa1511049.