Leukotriene antagonists as first-line or add-on asthma-controller therapy

David Price, Stanley D. Musgrave, Lee Shepstone, Elizabeth V. Hillyer, Erika J. Sims, Richard F. T. Gilbert, Elizabeth F. Juniper, Jon G. Ayres, Linda Kemp, Annie Blyth, Edward C. F. Wilson, Stephanie Wolfe, Daryl Freeman, H. Miranda Mugford, Jamie Murdoch, Ian Harvey

Research output: Contribution to journalArticle

188 Citations (Scopus)

Abstract

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 beta(2)-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.
Original languageEnglish
Pages (from-to)1695-1707
Number of pages13
JournalThe New England Journal of Medicine
Volume364
Issue number18
DOIs
Publication statusPublished - 5 May 2011

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Leukotriene Antagonists
Asthma
Glucocorticoids
Therapeutics
Quality of Life
Confidence Intervals
Primary Health Care
Pragmatic Clinical Trials

Cite this

Price, D., Musgrave, S. D., Shepstone, L., Hillyer, E. V., Sims, E. J., Gilbert, R. F. T., ... Harvey, I. (2011). Leukotriene antagonists as first-line or add-on asthma-controller therapy. The New England Journal of Medicine, 364(18), 1695-1707. https://doi.org/10.1056/NEJMoa1010846

Leukotriene antagonists as first-line or add-on asthma-controller therapy. / Price, David; Musgrave, Stanley D.; Shepstone, Lee; Hillyer, Elizabeth V.; Sims, Erika J.; Gilbert, Richard F. T.; Juniper, Elizabeth F.; Ayres, Jon G.; Kemp, Linda; Blyth, Annie; Wilson, Edward C. F.; Wolfe, Stephanie; Freeman, Daryl; Mugford, H. Miranda; Murdoch, Jamie; Harvey, Ian.

In: The New England Journal of Medicine, Vol. 364, No. 18, 05.05.2011, p. 1695-1707.

Research output: Contribution to journalArticle

Price, D, Musgrave, SD, Shepstone, L, Hillyer, EV, Sims, EJ, Gilbert, RFT, Juniper, EF, Ayres, JG, Kemp, L, Blyth, A, Wilson, ECF, Wolfe, S, Freeman, D, Mugford, HM, Murdoch, J & Harvey, I 2011, 'Leukotriene antagonists as first-line or add-on asthma-controller therapy', The New England Journal of Medicine, vol. 364, no. 18, pp. 1695-1707. https://doi.org/10.1056/NEJMoa1010846
Price D, Musgrave SD, Shepstone L, Hillyer EV, Sims EJ, Gilbert RFT et al. Leukotriene antagonists as first-line or add-on asthma-controller therapy. The New England Journal of Medicine. 2011 May 5;364(18):1695-1707. https://doi.org/10.1056/NEJMoa1010846
Price, David ; Musgrave, Stanley D. ; Shepstone, Lee ; Hillyer, Elizabeth V. ; Sims, Erika J. ; Gilbert, Richard F. T. ; Juniper, Elizabeth F. ; Ayres, Jon G. ; Kemp, Linda ; Blyth, Annie ; Wilson, Edward C. F. ; Wolfe, Stephanie ; Freeman, Daryl ; Mugford, H. Miranda ; Murdoch, Jamie ; Harvey, Ian. / Leukotriene antagonists as first-line or add-on asthma-controller therapy. In: The New England Journal of Medicine. 2011 ; Vol. 364, No. 18. pp. 1695-1707.
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AU - Price, David

AU - Musgrave, Stanley D.

AU - Shepstone, Lee

AU - Hillyer, Elizabeth V.

AU - Sims, Erika J.

AU - Gilbert, Richard F. T.

AU - Juniper, Elizabeth F.

AU - Ayres, Jon G.

AU - Kemp, Linda

AU - Blyth, Annie

AU - Wilson, Edward C. F.

AU - Wolfe, Stephanie

AU - Freeman, Daryl

AU - Mugford, H. Miranda

AU - Murdoch, Jamie

AU - Harvey, Ian

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N2 - 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 beta(2)-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.

AB - 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 beta(2)-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.

U2 - 10.1056/NEJMoa1010846

DO - 10.1056/NEJMoa1010846

M3 - Article

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EP - 1707

JO - The New England Journal of Medicine

JF - The New England Journal of Medicine

SN - 0028-4793

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