Rationale:
To resolve knowledge gaps and further understand asthma in older adults, we assessed the efficacy and safety of once-daily tiotropium Respimat® (tioR) add-on to at least inhaled corticosteroid (ICS) maintenance therapy in patients aged < 65 and ≥65 years with symptomatic asthma.
Methods:
Four Phase III, randomized, double-blind, placebo-controlled, parallel-group trials. PrimoTinA-asthma®: once-daily tioR 5 µg or placebo add-on to ICS (≥800 µg budesonide or equivalent) + a long-acting β2-agonist, for 48 weeks; MezzoTinA-asthma®: once-daily tioR 5 µg or 2.5 µg, twice-daily salmeterol via hydrofluoroalkane metered-dose inhaler 50 µg, or placebo (double-dummy design) add-on to ICS (400 – 800 µg budesonide or equivalent), for 24 weeks. Exclusion criteria included chronic obstructive pulmonary disease. Peak forced expiratory volume in 1 second (FEV1) within 3 hours post-dose and trough FEV1 responses at Week 24 were co-primary endpoints. We conducted a subgroup analysis of FEV1 responses in patients aged < 65 and ≥65 years.
Results:
Number of patients treated in < 65 and ≥65 years groups, respectively: PrimoTinA, n = 745, n = 167; MezzoTinA, n = 1996, n = 104. TioR 5 µg and 2.5 µg provided statistically significant improvements in peak FEV1 and trough FEV1 responses vs. placebo in patients aged < 65 and ≥65 years in all trials (Table). Frequency of adverse events (AEs) and serious AEs with tioR was comparable with that of placebo and similar between subgroups.
Tab. 1:
Improvements In peak FEV1(0 – 3h) and trough FEV1 with tiotropium Respimat® versus placebo at Week 24
|
|
Peak FEV1(0 – 3h)
adjusted mean difference ± SE. mL (95% CI), p value
|
Trough FEV1
adjusted mean difference ± SE, mL (95% CI), p value
|
|
|
< 65 years
|
≥65 years
|
< 65 years
|
≥65 years
|
|
PrimoTinA-asthma®ab
|
5 µg, n = 379
|
5 µg, n = 74
|
5 µg, n = 379
|
5 µg, n = 74
|
|
Tiotropium Respimat®
5 µg QD
|
100 ± 28 (45, 155).
0.0004
|
144 ± 39 (67, 221).
0.0003
|
87 ± 26 (37, 137).
0.0007
|
114 ± 38 (40, 189).
0 0028
|
|
MezzoTinA-asthma®ac
|
5 µg, n = 480; 2.5 µg, n = 492
|
5 µg, n = 33; 2.5 µg, n = 23
|
5 µg, n = 480; 2.5 µg, n = 492
|
5 µg, n = 33; 2.5 µg, n = 23
|
|
Tiotropium Respimat®
5 pg QD
|
187 ± 21 (146. 227).
< 0.0001
|
152 ± 53 (48. 257).
|
146 ± 22 (103. 190).
<n nnni
|
139 ± 57 (27.251).
0.0154
|
|
Tiotropium Respimat®
2.5 pg QD
|
222 ± 20 (182, 262),
< 0.0001
|
248 ± 57 (135, 360),
< 0.0001
|
179 ± 22 (136, 222),
< 0.0001
|
196 ± 61 (75, 316),
0.0016
|
|
Means are adjusted for treatment, center, visit, visit-by-treatment, baseline, and baseline-by-visit
aPooled data; bAdd-on to ICS + a long-acting β2-agonist; cAdd-on to ICS
CI, confidence interval; FEV1, forced expiratory volume in 1 second: FEV1(0 – 3h). FEV1 within 3 hours post-dose: QD, once daily; SE, standard error
|
Conclusions:
Once-daily tiotropium Respimat® add-on to at least ICS significantly improved lung function, with a safety profile comparable with that of placebo, in elderly and younger adults with symptomatic asthma.
Funding: The study was funded by Boehringer Ingelheim.
Previously submitted to the 113th Int. Conf. of the ATS, 2017
