Original Article
The Effect of Tiotropium in Symptomatic Asthma Despite Low- to Medium-Dose Inhaled Corticosteroids: A Randomized Controlled Trial

https://doi.org/10.1016/j.jaip.2015.08.017Get rights and content
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Background

Tiotropium, a once-daily long-acting anticholinergic bronchodilator, has demonstrated efficacy in patients with asthma who were symptomatic despite treatment with medium- to high-dose inhaled corticosteroids (ICS).

Objective

The objective of this study was to evaluate the efficacy and safety of once-daily tiotropium Respimat (5 μg or 2.5 μg), compared with placebo Respimat, as add-on therapy to low- to medium-dose ICS for adults with symptomatic asthma.

Methods

A phase III, double-blind, placebo-controlled trial was conducted (NCT01316380). Adults with symptomatic asthma receiving low- to medium-dose ICS (200-400 μg budesonide or equivalent dose) and a pre-bronchodilator forced expiratory volume in 1 second (FEV1) ≥60% and ≤90% of predicted normal were randomized to 12 weeks of treatment with once-daily tiotropium Respimat 5 μg or 2.5 μg, or placebo Respimat, as add-on therapy to ICS. The primary endpoint was peak FEV1(0-3h) response.

Results

In total, 464 patients were randomized (61% female; mean age 43 years; mean baseline FEV1 78% of predicted normal). After 12 weeks, both tiotropium Respimat doses were superior to placebo (adjusted mean difference from placebo: 5 μg, 128 mL; 2.5 μg, 159 mL; both P < .001). Both doses of tiotropium Respimat were also superior to placebo with regard to the secondary endpoints of adjusted mean trough FEV1 and FEV1 area under the curve(0-3h) responses, and the other endpoints of morning and evening peak expiratory flow. Adverse events were comparable across the treatment groups.

Conclusions

Once-daily tiotropium Respimat add-on therapy to low- to medium-dose ICS in adults with symptomatic asthma is an efficacious bronchodilator, and its safety and tolerability are comparable with those of placebo Respimat.

Key words

Tiotropium
Respimat
Anticholinergic
Mild
Asthma
Bronchodilators
ICS
Symptomatic
Control
GINA

Abbreviations used

ACQ-7
7-question Asthma Control Questionnaire
AE
Adverse event
AUC
Area under the curve
CI
Confidence interval
FVC
Forced vital capacity
FEV1
Forced expiratory volume in 1 second
GINA
Global Initiative for Asthma
ICS
Inhaled corticosteroids
LABA
Long-acting β2-agonist
Peak FEV1(0-3h)
Peak forced expiratory volume in 1 second within 3 hours of dosing
PEF
Peak expiratory flow
PEFAM
Morning peak expiratory flow
PEFPM
Evening peak expiratory flow
SE
Standard error

Cited by (0)

This work was supported by Boehringer Ingelheim. M. Engel, V. B. Zubek, Z. Blahova, and P. Moroni-Zentgraf are all employees of Boehringer Ingelheim. All authors were involved in the study design, analysis, interpretation, and writing of the manuscript, and in the decision to submit the article for publication.

Conflicts of interest: P. Paggiaro is on the AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, and Novartis boards; has received lecture fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, Mundipharma, Novartis, and Zambon. D. M. G. Halpin has received consulting fees from AstraZeneca, Almirall, Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Pfizer; has received travel support from Boehringer Ingelheim and Novartis. R. Buhl has received personal fees from AstraZeneca, Chiesi, GlaxoSmithKline, and Takeda; and has received grants and personal fees from Boehringer Ingelheim, Novartis, and Roche. M. Engel and P. Moroni-Zentgraf are employed by Boehringer Ingelheim, Ingelheim am Rhein, Germany. V. B. Zubek is employed by Boehringer Ingelheim, Ridgefield, Conn, USA. Z. Blahova is employed by Boehringer Ingelheim, Vienna, Austria. E. Pizzichini has received consultancy fees from Novartis, Boehringer Ingelheim, GlaxoSmithKline, and Merck Sharp & Dohme; and has received lecture fees from Novartis, Boehringer Ingelheim, GlaxoSmithKline, Merck Sharp & Dohme, Chiesi, and Ache.