2011 May 5- Leukotriene Antagonists as First-Line or Add-on Asthma-Controller Therapy
David Price, F.R.C.G.P., Stanley D. Musgrave, M.D., Lee Shepstone, Ph.D., Elizabeth V. Hillyer, D.V.M., Erika J. Sims, Ph.D., Richard F.T. Gilbert, M.R.C.G.P., Elizabeth F. Juniper, M.C.S.P., M.Sc., Jon G. Ayres, M.D., Linda Kemp, B.Sc., Annie Blyth, M.A., Edward C.F. Wilson, M.Sc., Stephanie Wolfe, M.Sc., R.G.N., Daryl Freeman, M.R.C.G.P., H. Miranda Mugford, Ph.D., Jamie Murdoch, Ph.D., and Ian Harvey, F.R.C.P.N Engl J Med 2011; 364:1695-1707
Background
Most randomized trials of treatment for asthma study highly selected patients under idealized conditions.
Methods
We conducted two parallel, multicenter, pragmatic trials to evaluate the real-world effectiveness of a leukotriene-receptor antagonist (LTRA) as compared with either an inhaled glucocorticoid for first-line asthma-controller therapy or a long-acting beta2-agonist (LABA) as add-on therapy in patients already receiving inhaled glucocorticoid therapy. Eligible primary care patients 12 to 80 years of age had impaired asthma-related quality of life (Mini Asthma Quality of Life Questionnaire [MiniAQLQ] score ≤6) or inadequate asthma control (Asthma Control Questionnaire [ACQ] score ≥1). We randomly assigned patients to 2 years of open-label therapy, under the care of their usual physician, with LTRA (148 patients) or an inhaled glucocorticoid (158 patients) in the first-line controller therapy trial and LTRA (170 patients) or LABA (182 patients) added to an inhaled glucocorticoid in the add-on therapy trial.
Results
Mean MiniAQLQ scores increased by 0.8 to 1.0 point over a period of 2 years in both trials. At 2 months, differences in the MiniAQLQ scores between the two treatment groups met our definition of equivalence (95% confidence interval [CI] for an adjusted mean difference, –0.3 to 0.3). At 2 years, mean MiniAQLQ scores approached equivalence, with an adjusted mean difference between treatment groups of –0.11 (95% CI, –0.35 to 0.13) in the first-line controller therapy trial and of –0.11 (95% CI, –0.32 to 0.11) in the add-on therapy trial. Exacerbation rates and ACQ scores did not differ significantly between the two groups.
Conclusions
Study results at 2 months suggest that LTRA was equivalent to an inhaled glucocorticoid as first-line controller therapy and to LABA as add-on therapy for diverse primary care patients. Equivalence was not proved at 2 years. The interpretation of results of pragmatic research may be limited by the crossover between treatment groups and lack of a placebo group.
Weblink
here
