Once-daily tiotropium Respimat® is well tolerated and efficacious over 52 weeks in Japanese patients with symptomatic asthma receiving inhaled corticosteroids (ICS)± long-acting β2-agonist (LABA): a randomized, double-blind, placebo-controlled study
Rationale: The present study evaluated long-term safety and efficacy of tiotropium Respimat® (tioR) in Japanese patients with moderate to severe symptomatic asthma, despite ICS ± LABA.
Methods: In thisPhase III trial across 54 Japanese centers (NCT01340209), patients were randomized to receive evening tioR 5 µg, 2.5 µg, or placebo (PBO), for 52 weeks. Eligible patients: seven-question Asthma Control Questionnaire mean score ≥1.5; forced expiratory volume in 1 second (FEV1) reversibility ≥12% and ≥200 mL; maintenance treatment with medium-dose ICS ± LABA. Primary endpoint: long-term safety; secondary endpoints included: trough FEV1; in-clinic peak expiratory flow rate (PEFR) using spirometry.
Results: 285 patients randomized, 264 completed treatment. Mean age: 44.5 years, gender: 61.8% female. Incidence of adverse events (AEs): similar across treatment groups; most AEs mild to moderate in intensity. Drug-related AEs in 8.8%, 5.3%, and 5.3% of the patients in the tioR 5 µg, 2.5 µg, and PBO groups, respectively. Serious AEs less frequent with tioR 5 µg (3.5%) and 2.5 µg (3.5%) vs PBO (15.8%). Adjusted mean trough FEV1 response significantly higher with tioR 5 µg vs PBO at Weeks 12, 36, and 52 (Week 52 difference: 0.112 L[95% confidence interval (CI): 0.018, 0.207; p = 0.0203]). At Weeks 24 and 52, adjusted mean PEFR significantly higher with tioR 5 µg vs PBO (difference: 28.981 L/min [95% CI: 5.047, 52.916; p = 0.0177] and 34.176 L/min [95% CI: 9.919, 58.432; p = 0.0058], respectively); no significant difference with tioR 2.5 µg regarding trough FEV1 and PEFR.
Conclusions: Long-term tioR treatment for 52 weeks has a safety profile comparable with that of PBO in Japanese patients with moderate to severe symptomatic asthma, despite ICS ± LABA. Improvements in lung function with tioR 5 µg vs PBO at Week 52 support the 5 µg dose as optimal for long-term therapy in this population.
Research funding source: Boehringer Ingelheim and Pfizer.
Presented at ATS congress 2014