Table 1.
Overview of ICS withdrawal studies
| Study | Publication year | Disease stage | Exacerbation risk | Pretreatment | n | Run-in | Treatment group
|
Concomitant bronchodilator treatment | Run-in | Exacerbation risk (ICS-discontinued group vs ICS-continued group) | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| ICS-discontinued group | ICS-continued group | ||||||||||
| Randomized controlled trials | |||||||||||
| Magnussen et al16 (WISDOM) |
2014 | Severe and very severe COPD (mean FEV1% predicted: 34.2±11) |
≥1 | 70% ICS; 65% LABA; 47% LAMA |
2,485 | 6 weeks TIO 18 µg od+SAL 50 µg bid+FP 500 µg bid |
TIO 18 µg od+SAL 50 µg bid+FP from 500 µg bid to 0 µg (PBO) in 3 steps of 6 weeks |
TIO 18 µg od+SAL 50 µg bid+FP 500 µg bid |
LAMA+LABA | 12 months | NS |
| Rossi et al40 (INSTEAD) |
2014 | Moderate COPD (mean FEV1% predicted: 64.1±8.18) |
0 | ≥3 months SAL/fluticasone propionate 50/500 µg bid |
581 | 2 weeks SAL/FP 50/500 µg bid |
IND 150 mg od | SAL/FP 50/500 µg bid | LABA | 6 months | NS |
| Choudhury et al41 (WISP) | 2007 | Primary care population: FEV1% predicted: <80 (mean: 54.1) | ICS for at least 6 months (median 8 years); 33% LABA |
260 | 2 weeks on regular ICS | PBO | FP 500 µg bid | 12 months | Increased risk | ||
| Wouters et al42 (COSMIC) |
2005 | Moderate and severe COPD (mean FEV1% predicted: 47.8) | ≥2 | 22% ICS; 3% LABA; 63% LABA/ICS |
373 | 3 months SAL/FP 50/500 µg bid |
SAL 50 µg bid | SAL/FP 50/500 µg bid | LABA | 12 months | Increased risk |
| van der Valk et al43 (COPE) |
2002 | Moderate to very severe COPD (mean FEV1% predicted: 56.8) | Mean 1.3 | 86% ICS ≥6 months; 46% LABA |
244 | 4 months FP 500 µg bid |
PBO | FP 500 µg bid | 50% on LABA | 6 months | Increased risk |
| O’Brien et al44 | 2001 | Severe COPD | Regular ICS use | 24 | PBO | BDP 336 µg/day | None | 6 weeks cross-over | NS (underpowered) | ||
| Observational trials | |||||||||||
| Vogelmeier et al45 (DACCORD) |
2017 | Mild to very severe COPD | Mixed | Mainly LABA/ICS or LAMA/LABA/ ICS |
1,258 | Mainly LAMA or LABA |
Mainly LABA/LAMA/ICS | LAMA/LABA | 2 years | NS | |
| Rossi et al46 (OPTIMO) |
2014 | FEV1 >50% (mean 71.2%) | <2 | LABA/ICS ≥1 year |
914 | Bronchodilator | LABA/ICS | LAMA (27%), LABA (44%), or LAMA+LABA (20%) |
6 months | NS | |
Abbreviations: ICS, inhaled corticosteroid; LABA, long-acting β2-adrenoreceptor agonists; LAMA, long-acting muscarinic receptor antagonist; TIO, tiotropium; SAL, salmeterol; FP, fluticasone propionate; PBO, placebo; NS, not significant; IND, indacaterol; BDP, beclomethasone dipropionate; FEV1, forced expiratory volume at the first second; OD, once daily; BID, bis in die (twice a day).