|
Jarad, 1999 [58]
|
MC, observational study; 8 weeks
|
COPD, post-BD FEV1 < 70% predicted (n = 272)
|
ICS withdrawal vs no previous ICS therapy
|
Increased risk of exacerbation after ICS withdrawal
|
|
van der Valk, 2002 (COPE) [59]
|
R, DB, SC, PC trial;4-month ICS run-in,6-month active treatment
|
Moderate-to-severe COPD, pre-BD FEV1 25–80% predicted, no exacerbations in past month (n = 244)
|
FP/IB vs PBO+ IB
|
Higher risk of exacerbation and deterioration in QoL after ICS withdrawal
|
|
Wouters, 2005 (COSMIC) [60]
|
R, DB, PG, MC trial; 3-month ICS/LABA run-in, 1-year active treatment
|
Moderate-to-severe COPD, pre-BD FEV1 30–70% predicted, ≥2 exacerbations in past year (n = 373)
|
FP/Sal vs Sal alone
|
Deterioration of symptoms and lung function after ICS withdrawal; no difference in the rate of exacerbations
|
|
Choudhury, 2007 (WISP) [61]
|
R, DB, PC trial; 2 week run-in on usual ICS; 1-year treatment
|
Primary care, moderate-to-severe COPD, post-BD FEV1 < 80% predicted, no exacerbations in past month(n = 260)
|
FP vs PBO
|
Higher risk of exacerbations and symptom deterioration after ICS withdrawal; no differences in lung function or QoL
|
|
Magnussen, 2014 (WISDOM) [63]
|
R, DB, PG, MC trial; 6-week ICS/LABA/LAMA run-in; 12-month active treatment
|
Severe-to-very severe COPD, FEV1 < 50%, ≥1 exacerbation in past year (n = 2485)
|
FP/Sal/Tio vs Sal/Tio + stepwise FP withdrawal
|
No differences in symptoms or exacerbations rate; significantly greater decrease in lung function with complete ICS withdrawal
|
|
Rossi, 2014 (INSTEAD) [65]
|
R, DB, DD, PG trial; 2-week ICS/LABA run-in; 26-week active treatment
|
Moderate COPD, GOLD stage II, no exacerbations in the past year (n = 581)
|
Switching from FP/Sal to Ind vs continuing FP/Sal
|
No differences in exacerbations, symptoms, lung function, QoL
|
|
Rossi, 2014 (OPTIMO) [66]
|
Prospective, real-life study; 6-month observation period
|
Mild-to-moderate COPD, on ICS + LABA for 1 year, FEV1 > 50%, <2 exacerbations in past year (n = 914)
|
ICS/LABA vs mainly LABD (91% LABA ± LAMA; 9% SABD ± theophylline)
|
ICS withdrawal not associated with worsening of exacerbation rates, lung function or symptoms
|
|
Suissa, 2015 [68]
|
Population-based, observational study; 4.9 years of follow-up
|
COPD treated with ICS (n = 103,386)
|
ICS withdrawal
|
Significant 37% reduction in serious pneumonia after ICS withdrawal; greatest reduction after FP withdrawal
|
|
Vogelmeier, 2013 (ILLUMINATE) [48]
|
R, DB, DD, PG, MC trial; 26 weeks
|
Moderate-to-severe COPD, GOLD stages II–III, no exacerbations in past year (n = 523)
|
Ind/Gly vs FP/Sal
|
Significantly improved lung function with Ind/Gly
|
|
Zhong, 2015 (LANTERN) [49]
|
R, DB, DD, PG, MC trial; 26 weeks
|
Moderate-to-severe COPD, GOLD stage II–III, ≤1 exacerbation in past year (n = 744)
|
Ind/Gly vs FP/Sal
|
Significantly reduced exacerbations and improved lung function with Ind/Gly; incidence of pneumonia 3-fold lower with Ind/Gly
|
|
Wedzicha, 2016 (FLAME) [50]
|
R, DB, DD, PG, MC trial; 4-week Tio run-in; 52-week active treatment
|
Moderate-to-severe COPD, post-BD FEV1 25–60% predicted, ≥1 exacerbation in past year (n = 3362)
|
Ind/Gly vs FP/Sal
|
Lower annual rate of exacerbation and longer time to first exacerbation with Ind/Gly; incidence of pneumonia higher with FP/Sal
|
|
Vogelmeier, 2017 (CRYSTAL) [69]
|
R, OL, MC trial; 12 weeks
|
Moderate COPD, ≤1 exacerbation in past year, on ICS/LABA, LABA, or LAMA therapy (n = 4389)
|
Switching to Gly or Ind/Gly vs continuing baseline therapy
|
Improved lung function and dyspnea with Ind/Gly vs ongoing ICS/LABA, LABA, or LAMA therapy
|
