Table 1 Overview of trials involving withdrawal of ICS in COPD, grouped by treatment comparators and disease severity
From: Appropriate use of inhaled corticosteroids in COPD: the candidates for safe withdrawal
Design | Patient population | N | Treatment groups | Duration of ICS use | Withdrawal | Outcomes |
|---|---|---|---|---|---|---|
Placebo-controlled trials | ||||||
 COPE (van der Valk, P et al.25) | ||||||
6-month, randomised, double-blind, parallel-group study | • Moderate-to-severe COPD (prebronchodilator FEV1 25–80% predicted) • No exacerbations in the month prior to enrolment | 244 |  • FP 500 μg b.i.d. • Placebo | FP for 4-month run-in period | Abrupt, on randomisation | Earlier exacerbation with placebo versus FP (HR 1.5; 95% CI 1.05, 2.1) |
 WISP (Choudhury AB et al.27) | ||||||
52-week, randomised, double-blind, placebo-controlled, parallel-group |  • Moderate-to-very-severe COPD (FEV1 <80% predicted) | 260 |  • FP 500 μg b.i.d. • Placebo | Median 8 years (prior to study entry) | Usual ICS stopped on study entry, and FP or placebo started | Increased exacerbation risk with placebo versus FP (RR 1.48; 95% CI 1.17, 1.86; P<0.001) |
Active comparator trials | ||||||
 INSTEAD (Rossi A et al.28) | ||||||
26-week, randomised, double-blind, double-dummy, parallel-group study | • Moderate COPD (FEV1 50–80% predicted) • No exacerbations for >1 year prior to study entry | 581 | • SFC 50/500 μg b.i.d. • Indacaterol 150 μg q.d. | SFC for ⩾3 months | Abrupt, on randomisation | Non-inferiority of indacaterol to SFC in trough FEV1 after 12 weeks (mean treatment difference −9 ml; 95% CI −45, 26) |
 COSMIC (Wouters EF et al.29) | ||||||
52-week, randomised, double-blind, parallel-group study | • Moderate-to-severe COPD (FEV1 30–70% predicted) • ⩾2 exacerbations in previous year | 373 | • SFC 50/500 μg b.i.d. • Salmeterol 50 μg b.i.d. | SFC for 3-month run-in period | Abrupt, on randomisation | Greater decline in FEV1 with salmeterol versus SFC (4.1%; 95% CI 1.6, 6.6; P<0.001) |
 WISDOM (Magnussen H et al.32) | ||||||
52-week, randomised, double-blind, parallel-group, active-controlled study | • Severe-to-very-severe COPD (FEV1<50% predicted) • 1 exacerbation in the year prior to screening | 2,485 | • Tiotropium 18 μg q.d.+salmeterol 50 μg b.i.d.+FP 500 μg b.i.d. • Tiotropium 18 μg q.d.+salmeterol 50 μg b.i.d. | Triple therapy for 6-week run-in period | Stepwise reduction in FP dose every 6 weeks | Non-inferiority of ICS withdrawal to ICS continuation in time to first moderate or severe exacerbation (HR 1.06; 95% CI 0.94, 1.19) |
