TY - JOUR
T1 - Step-Down Therapy for Asthma Well Controlled on Inhaled Corticosteroid and Long-Acting Beta-Agonist
T2 - A Randomized Clinical Trial
AU - American Lung Association Airways Clinical Research Centers
AU - Rogers, Linda
AU - Sugar, Elizabeth A.
AU - Blake, Kathryn
AU - Castro, Mario
AU - Dimango, Emily
AU - Hanania, Nicola A.
AU - Happel, Kyle I.
AU - Peters, Stephen P.
AU - Reibman, Joan
AU - Saams, Joy
AU - Teague, W. Gerald
AU - Wise, Robert A.
AU - Holbrook, Janet T.
N1 - Funding Information:
The Steering Committee of the American Lung Association Airways Clinical Research Centers designed, approved, and oversaw study implementation. GlaxoSmithKline funded the study with an unrestricted grant to the American Lung Association and also provided the active drug and placebo. GlaxoSmithKline reviewed the protocol before funding the trial but had no role in design, conduct, or analysis of the results. Study centers received institutional review board approval from their local boards and all participants signed institutional review board-approved consent statements. Participants younger than 18 years provided written assent. An independent data and safety monitoring committee that had access to unmasked data monitored the trial.
Publisher Copyright:
© 2017 American Academy of Allergy, Asthma & Immunology
PY - 2018/3
Y1 - 2018/3
N2 - Background: Stepping down therapy when asthma is well controlled on combination inhaled corticosteroids (ICSs) and long-acting beta-agonists (LABAs) is recommended, but it is not known whether lowering the ICS dose or stopping LABA is superior. Objective: To evaluate whether step-down therapy with LABA is superior to one without; and, secondarily, to evaluate whether reducing the ICS dose while maintaining LABA is noninferior to remaining on stable-ICS/LABA. Methods: The study was a randomized, double-masked 3-arm parallel group trial in participants aged 12 years or older. Following an 8-week run-in, 459 participants were randomly assigned to continue medium-dose ICS/LABA, reduced-dose ICS/LABA, or ICS alone (LABA-step-off) and followed for 48 weeks. The primary outcome was time to treatment failure, a composite of health care utilization, systemic corticosteroid use, increase in rescue therapy, decline in lung function, or participant or physician decision. Results: Time to treatment failure did not differ significantly between reduced- ICS/LABA and LABA-step-off (hazard ratio, 1.07; 95.3% CI, 0.69-1.65, P =.76). Nor was there a difference between stable-ICS/LABA and reduced-ICS/LABA (hazard ratio, 1.11; 95% CI, 0.70-1.76; P =.67), but the 10% noninferiority margin was exceeded. Lung function declines and hospitalization rates were significantly greater in the LABA-step-off group. Conclusions: The 2 step-down regimens did not differ in terms of treatment failure, although stopping LABA was associated with a decline in lung function and more hospitalizations. There was no evidence to support the noninferiority of reduced-ICS/LABA as compared with stable-ICS/LABA.
AB - Background: Stepping down therapy when asthma is well controlled on combination inhaled corticosteroids (ICSs) and long-acting beta-agonists (LABAs) is recommended, but it is not known whether lowering the ICS dose or stopping LABA is superior. Objective: To evaluate whether step-down therapy with LABA is superior to one without; and, secondarily, to evaluate whether reducing the ICS dose while maintaining LABA is noninferior to remaining on stable-ICS/LABA. Methods: The study was a randomized, double-masked 3-arm parallel group trial in participants aged 12 years or older. Following an 8-week run-in, 459 participants were randomly assigned to continue medium-dose ICS/LABA, reduced-dose ICS/LABA, or ICS alone (LABA-step-off) and followed for 48 weeks. The primary outcome was time to treatment failure, a composite of health care utilization, systemic corticosteroid use, increase in rescue therapy, decline in lung function, or participant or physician decision. Results: Time to treatment failure did not differ significantly between reduced- ICS/LABA and LABA-step-off (hazard ratio, 1.07; 95.3% CI, 0.69-1.65, P =.76). Nor was there a difference between stable-ICS/LABA and reduced-ICS/LABA (hazard ratio, 1.11; 95% CI, 0.70-1.76; P =.67), but the 10% noninferiority margin was exceeded. Lung function declines and hospitalization rates were significantly greater in the LABA-step-off group. Conclusions: The 2 step-down regimens did not differ in terms of treatment failure, although stopping LABA was associated with a decline in lung function and more hospitalizations. There was no evidence to support the noninferiority of reduced-ICS/LABA as compared with stable-ICS/LABA.
KW - Asthma
KW - Long-acting beta-agonist
KW - Step-down therapy
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U2 - 10.1016/j.jaip.2017.07.030
DO - 10.1016/j.jaip.2017.07.030
M3 - Article
C2 - 28974349
AN - SCOPUS:85043587365
SN - 2213-2198
VL - 6
SP - 633-643.e1
JO - Journal of Allergy and Clinical Immunology: In Practice
JF - Journal of Allergy and Clinical Immunology: In Practice
IS - 2
ER -