Summary of Clinical Trials Comparing LABA + LAMA with LABA + ICS
| Study | LABA + LAMA vs LABA + ICS | Number of Patients Randomized | Duration | Lung Function | Exacerbation |
|---|---|---|---|---|---|
| Magnussen et al, 2012 OCTANE46 | Tio (18 µg once daily) + SAL (50 µg twice daily) vs SFC (50/500 µg twice daily) | 344 | 8 weeks | Relative to SFC, Tio + SAL: -lowered postdose thoracic gas volume by 182 ± 44 mL after 4 weeks (P < .0001) and 87 ± 44 mL after 8 weeks (P < .05) -nonsignificantly increased exercise endurance time (20 ± 15 seconds at 4 weeks, 15 ± 13 seconds at 8 weeks) | Tio + SAL vs SFC 29 (8.4%) vs 24 (7.3%) |
| Vogelmeier et al, 2013 ILLUMINATE25 | IND + GLY (110/50 μg once daily) vs SFC (50/500 μg twice daily) | 522 | 26 weeks | IND + GLY vs SFC: -FEV1 AUC0 to 12 hours was significantly higher (treatment difference 138 mL; 95% CI: 100 to 176; P < .0001) | COPD worsening including exacerbation was the most frequent serious AE: 0.4% (1/13) vs 1.1% (3/14) for IND + GLY vs SFC groups, respectively |
| Hoshino et al, 201545 | Tio + IND (18/150 µg once daily) vs SFC (50/250 µg twice daily) | 46 | 16 weeks | Tio + IND vs SFC IC was significantly higher (P = .043) -increase in Ai/BSA (r = 0.535, P = .011) -decrease in WA/BSA (r = −0.688, P < .001), WA/Ao (r = −0.555, P = .002), and T/√BSA (r = −0.542, P = .007) | Not reported |
| Donohue et al, 201544 | UMEC/VI (62.5/25 µg once daily) vs SFC (50/250 µg twice daily) | 707 | 12 weeks | UMEC/VI vs SFC -statistically significant, clinically meaningful improvements in wmFEV1 (study 1: 74 mL; 95% CI: 38 to 110; study 2: 101 mL; 95% CI: 63 to 139) -trough FEV1 (study 1: 82 mL; 95% CI: 45 to 119; study 2: 98 mL; 95% CI: 59 to 137) (all P < .001) | Infrequent exacerbations |
| Singh et al, 201547 | UMEC/VI (62.5/25 µg once daily) vs SFC (50/500 µg twice daily) | 717 | 12 weeks | UMEC/VI vs SFC -wmFEV1 (80 mL; 95% CI: 46 to 113) -trough FEV1 (90 mL; 95% CI: 55 to 125) (both P < .001) | UMEC/VI vs SFC n = 8 vs 3 |
| Zhong et al, 2015 LANTERN26 | IND + GLY (110/50 μg once daily) vs SFC (50/500 μg twice daily) | 744 | 26 weeks | IND + GLY vs SFC -superiority for trough FEV1 (treatment difference = 75 mL; 95% CI: 44 to 107) -significant improvement in FEV1 AUC0 to 4 hours (treatment difference = 122 mL; 95% CI: 90 to 154) (both P < .001) | IND + GLY vs SFC n = 53 vs 81 |
| Beeh et al, 2016 ENERGITO43 | Tio + Olo (5/5 μg and 2.5/5 μg once daily) vs SFC (50/500 μg and 50/250 μg twice daily) | 229 | 6 weeks | Tio + Olo (5/5 μg) vs SFC (50/500 μg); Tio + Olo (5/5 μg) vs SFC (50/250 μg); Tio + Olo (2.5/5 μg) vs SFC (50/500 μg); and Tio + Olo (2.5/5 μg) vs SFC (50/250 μg) -FEV1 AUC0 to 12 adjusted mean (S.E.): 129 mL (11); 125 mL (11); 106 mL (11); 103 mL (11) (all P < .0001) | Not reported |
| Vogelmeier et al, 2016 AFFIRM48 | Aclidinium + formoterol (400/12 μg twice daily) vs SFC (50/500 μg twice daily) | 933 | 24 weeks | Aclidinium + formoterol vs SFC-superiority for peak FEV1 (treatment difference = 93 mL; P < .0001) | Aclidinium + formoterol vs SFC n = 74 vs 77 no difference in incidence |
| Wedzicha et al, 2016 FLAME29 | IND + GLY (110/50 μg once daily) vs SFC (50/500 μg twice daily) | 3362 | 52 weeks | IND + GLY vs SFC -significantly improved trough FEV1 (treatment difference = 62 mL; P < .001) | IND + GLY vs SFC Superiority for reducing the annual rate of all COPD exacerbations (3.59 vs 4.03; RR, 0.89; 95% CI: 0.83 to 0.96; P = .003) |
| Roche et al, 2017 FLAME27 | IND + GLY (110/50 μg once daily) vs SFC (50/500 μg twice daily) | 2048 | 52 weeks | Not reported | IND + GLY vs SFC Significant reduction in annualized rate of moderate or severe exacerbations (RR, 0.80 [P = .004] and 0.85 [P = .010], respectively) and all exacerbations (RR, 0.84 [P = .004] and 0.90 [P = .030], respectively) |
AE, adverse event; Ai, luminal area; Ao, total area of the airway; AUC, area under the curve; BSA, body surface area; CI, confidence interval; COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 second; GLY, glycopyrronium; ICS, inhaled corticosteroid; IND, indacaterol; IC, inspiratory capacity; LABA, long-acting β2-agonist; LAMA, long-acting antimuscarinic antagonist; Olo, olodaterol; RR, rate ratio; SAL, salmeterol; S.E., standard error; SFC, salmeterol + fluticasone; T, absolute wall thickness; Tio, tiotropium; UMEC, umeclidinium; VI, vilanterol; WA, airway wall area; wm, weighted mean.