Table 3.
Effect of ICS based therapies on the risk of COPD exacerbation
| Treatment [Reference] | Annual exacerbation rate | Comparator | Annual exacerbation rate | Reduction in exacerbations | Exacerbation endpoint | Patient population | |
|---|---|---|---|---|---|---|---|
| Exacerbation entry criteria (No./year) | FEV1 % predicted | ||||||
| ICS | |||||||
| FP [131] | 0.93 | Placebo | 0.73 | NS | Primary | NA | <90 % (post-BD) |
| FP [13] | 0.93 | Placebo | 1.13 | 18 % | Secondary (moderate or severe) | NA | <60 % (pre-BD) |
| FP [65] | 1.05 | Placebo | 1.30 | 19 % | Secondary (any) | ≥1 | 25–70 % (pre-BD) |
| FP [132] | 0.99 | Placebo | 1.32 | 25 % | Secondary (any) | NA | <85 % (post-BD) |
| LABA/ICS | |||||||
| SFC [133] | 0.44 | Salmeterol | 0.48 | NS | Primary (severe) | ≥1 (last 14 days) | <70 % (pre-BD) |
| SFC [134] | 1.10 | Salmeterol | 1.59 | 30.4 % | Primary (moderate or severe) | ≥1 | <50 % |
| SFC [13] | 0.85 | Placebo Salmeterol FP |
1.13 0.97 0.93 |
25 % 12 % 9 % |
Secondary (moderate or severe) | NA | <60 % (pre-BD) |
| SFC [65] | 0.97 | Placebo | 1.30 | 25 % | Secondary (moderate) | ≥1 | 25–70 % (pre-BD) |
| SFC [135] | 1.06 | Salmeterol | 1.53 | 30.5 % | Primary | ≥1 | <50 % |
| SFC [61, 136] | 1.28 | Tiotropium | 1.32 | NS | Primary (moderate or severe) | NA | <50 % (post-BD) |
| SFC [137] | 0.92 | Salmeterol | 1.4 | 35 % | Primary (moderate or severe) | ≥2 | <50 % (post-BD) |
| Bud/Form [80] | 1.38 | Placebo Formeterol Budesonide |
1.80 1.85 1.60 |
23.6 % NS NS |
Primary (all) | ≥1 | <50 % (pre-BD) |
| Bud/Form [81] | 1.42 | Placebo Formoterol Budesonide |
1.87 1.84 1.59 |
24 % 23 % NS |
Primary (severe) | ≥1 | <50 % |
| Bud/Form [138] | 0.70 (320/9 μg) 0.79 (160/9 μg) |
Formoterol | 1.07 | 34.6 % 25.9 % |
Primary (moderate or severe) | ≥1 | ≤50 % (pre-BD) |
| Bud/Form [139] | NR | Formoterol | NR | 36 % | Secondary (any) | ≥1 | ≤50 % (pre-BD) |
| FF/VI [79] | 0.81 | Vilanterol | 1.11 | 30 %(Pooled data) | Primary (moderate or severe) | ≥1 | <70 % (post-BD) |
| BDP/FOR [140] | 0.80 | Formoterol | 1.12 | 28 % | Primary (moderate or severe) | ≥1 | <50 % |
| BDP/FOR [141] | 0.41 | Bud/Form Formoterol | 0.42 0.43 |
NS | Primary | ≥1 | 30–50 % (post-BD) |
| Triple therapy | |||||||
| Tiotropium + salmeterol + FP [64] | 1.37 | Tiotropium | 1.61 | NS | Secondary (any) | ≥1 | <65 % (post-BD) |
Studies identified using PubMed search of key terms and limited to clinical trials published in English language and including at least 100 patients. Results were manually filtered for relevance and additional studies added at the author’s discretion. Reductions in exacerbations vs comparator were statistically significant unless otherwise stated (See Additional file 1 for detailed description of term used in searchs)
BD bronchodilator, BDP/FOR beclomethasone dipropionate/formoterol fumarate, FP fluticasone propionate, ICS inhaled corticosteroid, IND/GLY indacaterol/glycopyrronium, LABA long-acting β2-agonist, SFC salmeterol/fluticasone propionate, Bud/Form budesonide formoterol, FF/VI fluticasone furoate/vilanterol, NA not applicable, NR not reported, NS not significant