Table 6. Annualized rate and time to first exacerbation with LABA/LAMA FDCs versus placebo, TIO, and SFC26,27,28,29,31,32,38,40,47,50.
| Variable | IND/GLY 110/50 µg q.d. | VI/UMEC 25/62.5 µg q.d. | OLO/TIO 5/5 µg q.d.* | FOR/ACLI 12/400 µg b.i.d. | FF/GP 9.6/18 µg b.i.d. |
|---|---|---|---|---|---|
| Annualized rate of all exacerbations, RR | |||||
| Placebo | NA | NA | NA | NS | NA |
| TIO 18 µg q.d. | 0.86 | NS | NA | NA | NR† |
| SFC 50/500 µg b.i.d. | NS to 0.89 | NA | NA | NA | NA |
| Time to first exacerbation (all), HR | |||||
| Placebo | NA | 0.6 | NA | NA | NA |
| TIO 18 µg q.d. | NS | NS–0.5 | NA | NA | NA |
| SFC 50/500 µg b.i.d. | 0.84 | NA | NA | NA | NA |
| Annualized rate of moderate-to-severe exacerbations, RR | |||||
| Placebo | NA | NA | NA | NS | NA |
| TIO 18 µg q.d. | NS | NA | NS | NA | NA |
| SFC 50/500 µg b.i.d. | 0.69 to 0.83 | NA | NA | NA | NA |
| Time to first moderate or severe exacerbation, HR | |||||
| Placebo | NA | NA | NA | NA | NA |
| TIO 18 µg q.d. | NS | NA | NS | NA | NS |
| SFC 50/500 µg b.i.d. | 0.78 | NA | NA | NA | NA |
Data expressed as minimum and maximum mean value from all trials analyzed.
*For OLO/TIO 5/5 µg q.d. studies, TIO 5 µg q.d. used as comparator. †23% of patients in FF/GP 9.6/18 µg b.i.d. group and 25.1% in open-label TIO 18 µg q.d. group experienced exacerbation of any severity.
LABA/LAMA: long-acting β2-agonist/long-acting muscarinic antagonist; FDC: fixed-dose combination; TIO: tiotropium; SFC: salmeterol/fluticasone; IND/GLY: indacaterol/glycopyrronium; q.d.: once daily; VI/UMEC: vilanterol/umeclidinium; OLO/TIO: olodaterol/tiotropium; FOR/ACLI: formoterol/aclidinium; b.i.d.: twice daily; FF/GP: formoterol fumarate/glycopyrrolate; RR: rate ratio; NA: not available (no outcomes in any of the trials evaluated); NS: non-significant; NR: not reported (outcomes not reported in required units); HR: hazard ratio.