RSS-Feed abonnieren
DOI: 10.1055/s-0036-1572054
Tiotropium Plus Olodaterol Fixed-Dose Combination Therapy Provides Lung Function Benefits When Compared With Tiotropium Alone, Irrespective Of Prior Treatment With A Long-Acting Bronchodilator: Post Hoc Analyses Of Two 1-Year-Studies
Rationale: Tiotropium + olodaterol (T+O) is a novel once-daily, fixed-dose combination of the long-acting muscarinic antagonist (LAMA) tiotropium (T) and the long-acting β2-agonist (LABA) olodaterol, for use as maintenance treatment in chronic obstructive pulmonary disease (COPD). These post hoc analyses of data from the two pivotal 1-year TONADO studies determined whether treatment with a long-acting bronchodilator (LABD) prior to randomization affected the lung-function benefits of T+O 5/5 µg (via Respimat®) compared to T 5 µg (Respimat®).
Methods: 2124 patients had not received prior LABD treatment (T+O n = 426; T n = 454) and 3038 patients had (T+O n = 603, T n = 579; 60.6% LAMA, 78.8% LABA). Baseline characteristics for all patients and a sub-group with GOLD 2 lung-function impairment are presented in the Table. Forced expiratory volume in 1 second (FEV1) area under the curve from 0 – 3 hours (AUC0 – 3) response (change from baseline) and trough FEV1 response were primary end points in the studies.
Results: Comparable responses for both FEV1 AUC0 – 3 and trough FEV1 were observed in patients previously treated and untreated with LABD (see Table). The between-treatment differences (adjusted mean response [standard error (SE)]; mL) for no prior LABD and prior LABD treatment, respectively, were: 116 (13) and 105 (11) for FEV1 AUC0 – 3, and 76 (14) and 49 (11) for trough FEV1. In the GOLD 2 subgroup the between-treatment differences (adjusted mean response [standard error (SE)]; mL) for no prior LABD and prior LABD treatment, respectively, were: 114 (19) and 123 (17) for FEV1 AUC0 – 3, and 79 (20) and 61 (18) for trough FEV1.
Conclusions: Our analyses demonstrate the robust lung-function efficacy of T+O, compared with T alone, independent of the requirement for, or prior use of, LABD. These findings suggest a benefit of combination therapy over the mono-product as a first-line maintenance treatment.
No prior LABD treatment |
Prior LABD treatment |
|||||||
All |
GOLD 2 |
All |
GOLD 2 |
|||||
T+O |
T |
T+O |
T |
T+O |
T |
T+O |
T |
|
Baseline characteristics |
||||||||
n |
426 |
454 |
228 |
240 |
603 |
579 |
274 |
277 |
Age (years), mean ± SD |
62.7 ± 8.3 |
62.6 ± 8.8 |
63.0 ± 8.2 |
62.5 ± 8.9 |
64.6 ± 8.3 |
64.8 ± 8.2 |
65.3 ± 8.9 |
64.8 ± 8.7 |
Male, n (%) |
291 (68.3) |
338 (74.4) |
148 (64.9) |
160 (66.7) |
442 (73.3) |
417 (72.0) |
202 (73.7) |
180 (65.0) |
Ex-smoker, n (%) |
241 (56.6) |
278 (61.2) |
117 (51.3) |
128 (53.3) |
388 (64.3) |
385 (66.5) |
176 (64.2) |
179 (64.6) |
Post-bronchodilator FEV 1 (L), mean ± SD |
1.38 ± 0.52 |
1.43 ± 0.54 |
1.72 ± 0.44 |
1.77 (0.47) |
1.32 (0.50) |
1.32 (0.51) |
1.69 (0.44) |
1.69 (0.45) |
Post-bronchodilator FEV 1 (% predicted), mean ± SD |
50.7 ± 16.0 |
50.8 ± 15.7 |
63.2 ± 8.8 |
63.1 ± 8.4 |
48.3 ± 14.7 |
48.8 ± 15.6 |
62.0 ± 7.4 |
62.7 ± 8.1 |
Reversibility (mL), mean ± SD |
158 ± 160 |
166 ± 144 |
175 ± 156 |
184 ± 163 |
169 ± 138 |
174 ± 147 |
201 ± 151 |
196 ± 170 |
Lung function after 24 weeks of treatment |
||||||||
Adjusted mean FEV1 AUC0 – 3, (mL)± SE |
270 ± 10 |
154 ± 9 |
289 ± 13 |
175 ± 13 |
256 ± 8 |
150 ± 8 |
302 ± 12 |
179 ± 12 |
Adjusted mean trough FEV1 (mL)± SE |
148 ± 10 |
72 ± 10 |
146 ± 14 |
68 ± 14 |
134 ± 8 |
86 ± 8 |
156 ± 13 |
95 ± 13 |
SD, standard deviation |
Funding: Boehringer Ingelheim