Tiotropium Respimat®: efficacy in elderly asthma patients

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 FEV_{1(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