Fluticasone-salmeterol combination therapy safe and efficacious for asthma: The AUSTRI trial

1. For patients with moderate-to-severe asthma, fluticasone-salmeterol combination therapy was not associated with a higher risk of serious asthma-related events than fluticasone alone.

2. Fluticasone-salmeterol combination therapy, especially during adolescence, is associated with a significantly lower risk of severe asthma exacerbations.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Despite the efficacy of long-acting beta agonists (LABA) for the treatment of asthma, there has been controversy regarding a possible association between chronic use and increased mortality. Numerous meta-analyses have linked chronic LABA use to increased asthma-related deaths due to a delay in recognition of worsening airway inflammation. Yet, few studies have adequately controlled for the concomitant use of glucocorticoids.

The AUSTRI trial compared the safety and efficacy of fluticasone alone and fluticasone-salmeterol combination therapy in patients with moderate-to-severe asthma. The results indicated a decreased risk of severe asthma exacerbations using fluticasone-salmeterol compared to fluticasone alone without a significant difference in serious adverse asthma-related events.

This was a randomized controlled, double-blinded trial. The generalizability may be limited by the use of only moderate-to-severe asthmatic patients and strict medication adherence during the trial. In addition, the trial only lasted 26 weeks and may be insufficient to monitor long-term adverse events.

Click to read the study, published today in NEJM

Relevant Reading: Meta-analysis of the risk of mortality with salmeterol and the effect of concomitant inhaled corticosteroid therapy

In-Depth [randomized controlled trial]: This multi-center, randomized controlled trial was conducted in 710 centers across 33 countries. Eligible patients had at least a 1-year history of moderate-to-severe asthma and had received systemic glucocorticoids or been hospitalized in the past 12 months for asthma exacerbation. Patients were randomized to fluticasone-salmeterol combination or fluticasone alone treatment. Researchers were double-blinded with respect to treatment. The primary safety end-point used was a composite of death, endotracheal intubation, and hospitalization. The primary efficacy end point was the first severe asthma exacerbation based on systemic glucocorticoid use for 3 days or hospitalization.

No difference in the composite safety end point was found between the two groups (fluticasone-salmeterol = 34, fluticasone = 33) or any of the individual components. No asthma related deaths were reported in either arm. Subgroup analysis indicated greater efficacy in asthma control using fluticasone-salmeterol combination therapy in well controlled patients on previous inhaled glucocorticoid plus LABA therapy (HR=0.76; 95% [CI]:0.65-0.91; p=0.002). This analysis also indicated better control in all patients age 12-17 year (HR=0.65; 95% [CI]: 0.44-0.95; p=0.03) and 18-64 year (HR=0.81; 95% [CI]: 0.71-0.93; p=0.002). An overall 21% lower risk of asthma exacerbations was found among patients receiving combination therapy than among those receiving fluticasone alone (HR= 0.79; 95% [CI]: 0.70 to 0.89).

Image: PD

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