Overall summary of adverse events (treated set).

<p>^aPatients were randomised 2:2:1 to the tiotropium Respimat 5 μg, tiotropium Respimat 2.5 μg and placebo Respimat groups, respectively.</p><p>^bAs determined by the investigator.</p><p>^cElevation of aspartate aminotransferase and/or alanine aminotransferase ≥3 × upper limit of normal combined with elevated total bilirubin ≥2 × upper limit of normal at the same visit.</p><p>^dAsthma worsening.</p><p>AE, adverse event.</p><p>Overall summary of adverse events (treated set).</p

Long-Term Once-Daily Tiotropium Respimat® Is Well Tolerated and Maintains Efficacy over 52 Weeks in Patients with Symptomatic Asthma in Japan: A Randomised, Placebo-Controlled Study

<div><p>Background</p><p>This study assessed the long-term safety and efficacy of tiotropium Respimat, a long-acting inhaled anticholinergic bronchodilator, in asthma, added on to inhaled corticosteroids (ICS) with or without long-acting β₂-agonist (LABA).</p><p>Methods</p><p>285 patients with symptomatic asthma, despite treatment with ICS±LABA, were randomised 2:2:1 to once-daily tiotropium 5 μg, tiotropium 2.5 μg or placebo for 52 weeks (via the Respimat SoftMist inhaler) added on to ICS±LABA, in a double-blind, placebo-controlled, parallel-group study (NCT01340209). Primary objective: to describe the long-term safety profile of tiotropium. Secondary end points included: trough forced expiratory volume in 1 second (FEV₁) response; peak expiratory flow rate (PEFR) response; seven-question Asthma Control Questionnaire (ACQ-7) score.</p><p>Results</p><p>At Week 52, adverse-event (AE) rates with tiotropium 5 μg, 2.5 μg and placebo were 88.6%, 86.8% and 89.5%, respectively. Commonly reported AEs with tiotropium 5 μg, 2.5 μg and placebo were nasopharyngitis (48.2%, 44.7%, 42.1%), asthma (28.9%, 29.8%, 38.6%), decreased PEFR (15.8%, 7.9%, 21.1%), bronchitis (9.6%, 13.2%, 7.0%), pharyngitis (7.9%, 13.2%, 3.5%) and gastroenteritis (10.5%, 3.5%, 5.3%). In the tiotropium 5 μg, 2.5 μg and placebo groups, 8.8%, 5.3% and 5.3% of patients reported drug-related AEs; 3.5%, 3.5% and 15.8% reported serious AEs. Asthma worsening was the only serious AE reported in more than one patient. At Week 52, adjusted mean trough FEV₁ and trough PEFR responses were significantly higher with tiotropium 5 μg (but not 2.5 μg) versus placebo. ACQ-7 responder rates were higher with tiotropium 5 μg and 2.5 μg versus placebo at Week 24.</p><p>Conclusions</p><p>The long-term tiotropium Respimat safety profile was comparable with that of placebo Respimat, and associated with mild to moderate, non-serious AEs in patients with symptomatic asthma despite ICS±LABA therapy. Compared with placebo, tiotropium 5 μg, but not 2.5 μg, significantly improved lung function and symptoms, supporting the long-term efficacy of the 5 μg dose.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="https://www.clinicaltrials.gov/ct2/show/NCT01340209?term=NCT01340209&rank=1" target="_blank">NCT01340209</a></p></div

CONSORT diagram.

<p>CONSORT diagram.</p

Frequency of adverse events with incidence ≥4% in any treatment group (treated set).

<p>^aPatients were randomised 2:2:1 to the tiotropium Respimat 5 μg, tiotropium Respimat 2.5 μg and placebo Respimat groups, respectively.</p><p>^bThe preferred term ‘asthma’ summarises several lowest level terms.</p><p>Frequency of adverse events with incidence ≥4% in any treatment group (treated set).</p

Frequency of cardiac adverse events (treated set).

<p>^aPatients were randomised 2:2:1 to the tiotropium Respimat 5 μg, tiotropium Respimat 2.5 μg and placebo Respimat groups, respectively.</p><p>^bOne event from each category occurred in a single patient prior to Day 59.</p><p>Frequency of cardiac adverse events (treated set).</p

Additional file 2: of Physician perspectives on the burden and management of asthma in six countries: The Global Asthma Physician Survey (GAPS)

Table S1. Reasons given for the perceived improved outlook for asthma patients in the last 10 years. Table S2. Products approved for maintenance and reliever treatment of asthma in the countries studied. (PDF 202 kb