Quadrupling inhaled glucocorticoid dose to abort asthma exacerbations

McKeever, Tricia; Mortimer, Kevin; Wilson, Andrew; Walker, Samantha; Brightling, Christopher; Skeggs, Andrew; Pavord, Ian; Price, David; Duley, Lelia; Thomas, Mike; Bradshaw, Lucy; Higgins, Bernard; Haydock, Rebecca; Mitchell, Eleanor; Devereux, Graham; Harrison, Timothy

Abstract

Copyright © 2018 Massachusetts Medical Society. BACKGROUND Asthma exacerbations are frightening for patients and are occasionally fatal. We tested the concept that a plan for patients to manage their asthma (self-management plan), which included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate, would reduce the incidence of severe asthma exacerbations among adults and adolescents with asthma. METHODS We conducted a pragmatic, unblinded, randomized trial involving adults and adolescents with asthma who were receiving inhaled glucocorticoids, with or without addon therapy, and who had had at least one exacerbation in the previous 12 months. We compared a self-management plan that included an increase in the dose of inhaled glucocorticoids by a factor of 4 (quadrupling group) with the same plan without such an increase (non-quadrupling group), over a period of 12 months. The primary outcome was the time to a first severe asthma exacerbation, defined as treatment with systemic glucocorticoids or an unscheduled health care consultation for asthma. RESULTS A total of 1922 participants underwent randomization, of whom 1871 were included in the primary analysis. The number of participants who had a severe asthma exacerbation in the year after randomization was 420 (45%) in the quadrupling group as compared with 484 (52%) in the non-quadrupling group, with an adjusted hazard ratio for the time to a first severe exacerbation of 0.81 (95% confidence interval, 0.71 to 0.92; P = 0.002). The rate of adverse effects, which were related primarily to local effects of inhaled glucocorticoids, was higher in the quadrupling group than in the non-quadrupling group. CONCLUSIONS In this trial involving adults and adolescents with asthma, a personalized selfmanagement plan that included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate resulted in fewer severe asthma exacerbations than a plan in which the dose was not increased.

Citation

McKeever, T., Mortimer, K., Wilson, A., Walker, S., Brightling, C., Skeggs, A., Pavord, I., Price, D., Duley, L., Thomas, M., Bradshaw, L., Higgins, B., Haydock, R., Mitchell, E., Devereux, G., & Harrison, T. (2018). Quadrupling inhaled glucocorticoid dose to abort asthma exacerbations. New England Journal of Medicine, 378(10), 902-910. https://doi.org/10.1056/NEJMoa1714257

• Journal Article Type: Article
• Acceptance Date: Jan 26, 2018
• Online Publication Date: Mar 3, 2018
• Publication Date: Mar 8, 2018
• Deposit Date: Mar 22, 2018
• Publicly Available Date: Sep 4, 2018
• Journal: New England Journal of Medicine
• Print ISSN: 0028-4793
• Electronic ISSN: 1533-4406
• Publisher: Massachusetts Medical Society
• Peer Reviewed: Peer Reviewed
• Volume: 378
• Issue: 10
• Pages: 902-910
• DOI: https://doi.org/10.1056/NEJMoa1714257
• Public URL: https://nottingham-repository.worktribe.com/output/919150
• Publisher URL: http://www.nejm.org/doi/10.1056/NEJMoa1714257
• Additional Information: From The New England Journal of Medicine, Tricia McKeever, Ph.D., Kevin Mortimer, Ph.D., Andrew Wilson, M.D., Samantha Walker, Ph.D., Christopher Brightling, Ph.D., Andrew Skeggs, B.Sc., Ian Pavord, F.Med.Sci., David Price, F.R.C.G.P., Lelia Duley, M.D., Mike Thomas, Ph.D., Lucy Bradshaw, M.Sc., Bernard Higgins, Ph.D., Rebecca Haydock, B.Sc., Eleanor Mitchell, B.A., Graham Devereux, Ph.D., and Timothy Harrison, M.D., Quadrupling inhaled glucocorticoid dose to abort asthma exacerbations, 378: 902-910. Copyright © 2018 Massachusetts Medical Society. Reprinted with permission.