Table 3 Tiotropium/olodaterol combination – summary table of evidence
From: Tiotropium in chronic obstructive pulmonary disease – a review of clinical development
Study | Patients (N) | Treatment arms | Primary endpoint results | Proportion of patients with adverse events | Conclusion of the study |
|---|---|---|---|---|---|
Buhl 2015 [95] | 5162 | • Tiotropium+olodaterol 2.5/5 μg QD • Tiotropium+olodaterol 5/5 μg QD • Tiotropium 2.5 μg QD • Tiotropium 5 μg QD • Olodaterol 5 μg QD | • FEV1 AUC0–3 response: o Tiotropium+olodaterol 2.5/5 μg vs olodaterol 5 μg, 0.115 L; vs tiotropium 2.5 μg, 0.111 L; and vs tiotropium 5 μg, 0.097 L (p < 0.0001 for all comparisons) o Tiotropium+olodaterol 5/5 μg vs olodaterol 5 μg, 0.128 L and vs tiotropium 5 μg, 0.110 L (p < 0.0001 for both) • Trough FEV1 response: o Tiotropium+olodaterol 2.5/5 μg: vs olodaterol 5 μg, 0.062 L; vs tiotropium 2.5 μg, 0.045 L; vs tiotropium 5 μg, 0.038 L (p < 0.0001 for all comparisons) o Tiotropium+olodaterol 5/5 μg: vs olodaterol 5 μg, 0.085 L; vs tiotropium 5 μg, 0.060 L (p < 0.0001 for both comparisons) • SGRQ total score: o Tiotropium+olodaterol 5/5 μg: vs olodaterol 5 μg, − 1.693 (p = 0.0022); vs tiotropium 5 μg, − 1.233 (p = 0.0252) o Tiotropium+olodaterol 2.5/5 μg vs individual components was not significant for all comparisons | 74.7% vs 74.0% vs 73.4% vs 73.3% vs 76.6% | Tiotropium+olodaterol improved lung function and HRQoL compared with monocomponents |
Beeh 2015 [96] | 259 | • Tiotropium+olodaterol 2.5/5 μg QD • Tiotropium+olodaterol 5/5 μg QD • Tiotropium 2.5 μg QD • Tiotropium 5 μg QD • Olodaterol 5 μg QD • Placebo | • FEV1 AUC0–24 response: o Tiotropium+olodaterol 2.5/5 μg: vs olodaterol 5 μg, 0.111 L; vs tiotropium 2.5 μg, 0.124 L; vs tiotropium 5 μg, 0.107 L; vs placebo, 0.277 L (p < 0.001 for all comparisons) o Tiotropium+olodaterol 5/5 μg: vs olodaterol 5 μg, 0.115 L; vs tiotropium 2.5 μg, 0.127 L; vs tiotropium 5 μg, 0.110 L; vs placebo, 0.280 L (p < 0.0001 for all comparisons) | 36.0% vs 37.4% vs 39.4% vs 44.2% vs 37.7% vs 46.4% | Tiotropium+olodaterol improved lung function over 24 h compared with monocomponents |
O’Donnell 2017 [97] | 586 | • Tiotropium+olodaterol 2.5/5 μg QD • Tiotropium+olodaterol 5/5 μg QD • Tiotropium 5 μg QD • Olodaterol 5 μg QD • Placebo | • Inspiratory capacity: o Tiotropium+olodaterol 2.5/5 μg: vs olodaterol 5 μg, 0.090 L; vs tiotropium 5 μg, 0.092 L; vs placebo, 0.245 L (p < 0.0001 for all comparisons) o Tiotropium+olodaterol 5/5 μg: vs olodaterol 5 μg, 0.099 L; vs tiotropium 5 μg, 0.101 L; vs placebo, 0.254 L (p < 0.0001 for all comparisons) • Exercise endurance time during constant work-rate cycle ergometry (improvement): o Tiotropium+olodaterol 2.5/5 μg: vs olodaterol 5 μg, 7.3% (p < 0.01); vs tiotropium 5 μg, 3.5%; vs placebo, 19.2% (p < 0.0001) o Tiotropium+olodaterol 5/5 μg: vs olodaterol 5 μg, 5.6% (p < 0.05); vs tiotropium 5 μg, 1.9%; vs placebo, 17.3% (p < 0.0001) | 36.3% vs 40.0% vs 38.3% vs 40.2% vs 40.8% | Tiotropium+olodaterol improved lung hyperinflation and exercise tolerance compared with monotherapies |
Maltais 2018 [98] | 404 | • Tiotropium+olodaterol 2.5/5 μg QD • Tiotropium+olodaterol 5/5 μg QD • Placebo | • Endurance time during constant work-rate cycle ergometry: o Tiotropium+olodaterol 5/5 μg vs placebo, 14% (p = 0.02) o Tiotropium+olodaterol 2.5/5 μg vs placebo, 9% (p = 0.14) | 54.9% vs 43.9% vs 50.8% | Tiotropium+olodaterol improved endurance time compared with placebo during cycle ergometry |
Singh 2015 [99] | 1621 | • Tiotropium+olodaterol 2.5/5 μg QD • Tiotropium+olodaterol 5/5 μg QD • Tiotropium 5 μg QD • Placebo | • SGRQ total score (difference): o Tiotropium+olodaterol 5/5 μg: vs tiotropium 5 μg, − 2.10 (p < 0.01); vs placebo, − 4.67 (p < 0.0001) o Tiotropium+olodaterol 2.5/5 μg: vs tiotropium 5 μg, − 1.27; vs placebo, − 3.85 (p < 0.0001) • FEV1 AUC0–3 response: o Both tiotropium+olodaterol 2.5/5 μg and 5/5 μg significantly improved (p < 0.0001) FEV1 AUC0–3 response compared with placebo and tiotropium 5 μg | OTEMTO 1: 42.6% vs 44.8% vs 44.3% vs 51.5% OTEMTO 2: 45.5% vs 43.1% vs 45.8% vs 46.0% | Tiotropium+olodaterol improved lung function and QoL compared with placebo and tiotropium |
Beeh 2016 [100] | 229 | • Tiotropium+olodaterol 2.5/5 μg QD • Tiotropium+olodaterol 5/5 μg QD • Salmeterol/fluticasone 50/500 μg BID • Salmeterol/fluticasone 50/250 μg BID | • FEV1 AUC0–12 response: o 0.295 L vs 0.317 L vs 0.188 L vs 0.192 L (p < 0.0001 for comparisons of tiotropium+olodaterol vs salmeterol/fluticasone) | 34.4% vs 33.9% vs 37.0% vs 29.7% | Tiotropium+olodaterol QD provided superior improvement in lung function compared with salmeterol/fluticasone BID |
Troosters 2018 [101] | 303 | • Tiotropium+olodaterol 5/5 μg QD • Tiotropium+olodaterol 5/5 μg QD plus 8 weeks of ExT • Tiotropium 5 μg • Placebo | • Exercise endurance time by shuttle walk test (increase): o Tiotropium+olodaterol 5/5 μg QD vs placebo, 29.2% (p = 0.0109) o Tiotropium+olodaterol 5/5 μg QD plus 8 weeks of ExT vs placebo, 45.8% (p = 0.0002) o Tiotropium 5 μg vs placebo, 4.1% (p = 0.6895) | 57.9% vs 64.5% vs 67.1% vs 61.3% | In patients taking part in a self-management behavior-modification program, tiotropium+olodaterol improved exercise endurance time compared with placebo |
Calverley 2018 [102] | 7880 | • Tiotropium+olodaterol 5/5 μg QD • Tiotropium 5 μg QD | • Rate of moderate and severe COPD exacerbations: o 0.90 vs 0.97 (rate ratio, 0.93; p = 0.0498) | 74% vs 75% | Tiotropium+olodaterol reduced exacerbation rate compared with tiotropium, but not to a significant extent |