Burden of Asthma and Role of 2.5 µg Tiotropium Respimat(®) as an Add-On Therapy: A Systematic Review of Phase 2/3 Trials

哮喘负担及 2.5 µg 噻托溴铵 Respimat® 作为附加疗法的作用:2/3 期试验的系统评价

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Abstract

INTRODUCTION: Tiotropium, a long-acting muscarinic antagonist, is approved for maintenance treatment of asthma in patients at least 6 years of age in the USA. We systematically reviewed published evidence on the efficacy and safety of 2.5 µg tiotropium Respimat(®) add-on therapy to inhaled corticosteroid (ICS) with or without additional controller medication(s) in children, adolescents, and adults with asthma. METHODS: We searched PubMed from inception until October 3, 2018, for phase 2 and 3 randomized controlled trials (RCTs) evaluating the effects of 2.5 µg tiotropium Respimat(®) on lung function parameters in patients with asthma. We extracted adjusted mean differences for lung function data and adverse events (AEs) from relevant articles. RESULTS: Overall, 11 RCTs (three phase 2 and eight phase 3 studies) including 3244 patients (2.5 µg tiotropium Respimat(®), n = 1642; placebo, n = 1602) met the predefined inclusion criteria. Once-daily 2.5 µg tiotropium Respimat(®) improved lung function parameters, including peak and trough forced expiratory volume in 1 s and peak and trough forced vital capacity, versus placebo. Overall, the safety profile of 2.5 µg tiotropium Respimat(®) was comparable to that of placebo, with the most commonly reported AEs being asthma worsening, reduction in peak expiratory rate, nasopharyngitis, and respiratory tract infections. CONCLUSION: On the basis of the results of phase 2 and 3 studies, 2.5 µg tiotropium Respimat(®) as add-on to ICS therapy was safe and associated with consistent improvements in lung function in patients with asthma of varying severities across different age groups. FUNDING: Development of the manuscript was funded by Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI).

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