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

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 mu g 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 mu g 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 mu g tiotropium Respimat, n = 1642; placebo, n = 1602) met the predefined inclusion criteria. Once-daily 2.5 mu g 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 mu g 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 mu g 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).