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Table 1 Studies of inhaled corticosteroid (ICS) withdrawal in patients with chronic obstructive pulmonary disease

From: A proposal for the withdrawal of inhaled corticosteroids in the clinical practice of chronic obstructive pulmonary disease

Author, year (study name) Study design; duration Study population Treatment Main findings
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
  1. BD bronchodilator, COPD chronic obstructive pulmonary disease, DB double-blind, DD double-dummy, FEV 1 forced expiratory volume in 1 s, FP fluticasone propionate, Gly glycopyrronium, IB ipratropium bromide, ICS inhaled corticosteroid, Ind indacterol, LABA long-acting β-agonist, LAMA long-acting muscarinic antagonist, LABD long-acting bronchodilator, MC multicenter, PBO placebo, PC placebo-controlled, PDE phosphodiesterase, PG parallel-group, Pred prednisolone, QoL quality of life, R randomized, Sal salmeterol, SABD short-acting bronchodilator, Tio tiotropium