LOCSS trial: Once-daily fluticasone plus salmeterol superior to montelukast as step-down therapy for mild persistent asthma

August 1, 2007

In a multicenter, randomized, double-blind, controlled trial, investigators demonstrated that in patients whose asthma was well controlled with the use of fluticasone twice daily, switching to fluticasone plus salmeterol once daily did not increase the rates of treatment failure, but switching to montelukast once daily resulted in a 60% increased risk of treatment failure.

Key Points

In a multicenter, randomized, double-blind, controlled trial, investigators demonstrated that in patients whose asthma was well controlled with the use of fluticasone twice daily, switching to fluticasone plus salmeterol once daily did not increase the rates of treatment failure, but switching to montelukast once daily resulted in a 60% increased risk of treatment failure.

These results from the Leukotriene or Corticosteroid or Corticosteroid-Salmeterol (LOCSS) trial were published in the New England Journal of Medicine (NEJM).

The LOCSS trial included 500 patients who received fluticasone 100 mcg twice daily for 4 to 6 weeks during an open-label run-in period. Those patients whose asthma was well controlled at the end of the run-in period continued to the double-blind phase of the trial and were randomized to receive 16 weeks of treatment with either continued inhaled fluticasone 100 mcg twice daily (n=169), fluticasone 100 mcg plus salmeterol 50 mcg once daily (n=165), or montelukast 5 mg (patients aged 6–14 y) or 10 mg (patients aged ≥15 y) once daily (n=169). The primary study end point was the incidence of treatment failure.

The authors stated that the treatment benefits of once-daily inhaled fluticasone plus salmeterol need to be weighed against the convenience of once-daily oral montelukast, taking into consideration patient and physician preferences and cost.

The National Heart Lung and Blood Institute (NHLBI) treatment guidelines for asthma recommend the use of inhaled corticosteroids as first-line therapy for persistent asthma. When acceptable asthma control has been achieved, the guidelines recommend that patients be stepped down in therapy to simplify treatment, increase patient adherence, and minimize adverse drug events.

SOURCES

Peters SP, Anthonisen N, Castro M, et al; for the American Lung Association Asthma Clinical Research Centers. Randomized comparison of strategies for reducing treatment in mild persistent asthma. N Engl J Med. 2007;356:2027–2039.

National Heart Lung and Blood Institute. Expert panel report: Guidelines for the diagnosis and management of asthma: Update on selected topics 2002. NIH publication No. 02-5074. http:// http://www.nhlbi.nih.gov/guidelines/asthma/asthupdt.htm. Published June 2003. Accessed July 2, 2007.