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

Adv Ther. 2019 Oct;36(10):2587-2599. doi: 10.1007/s12325-019-01062-w. Epub 2019 Aug 21.

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).

Keywords: Asthma; Step-up therapy; Tiotropium.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Administration, Inhalation
  • Adult
  • Asthma / drug therapy*
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / therapeutic use*
  • Child
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Drug Therapy, Combination
  • Forced Expiratory Volume / drug effects
  • Humans
  • Muscarinic Antagonists / administration & dosage
  • Muscarinic Antagonists / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Tiotropium Bromide / administration & dosage
  • Tiotropium Bromide / therapeutic use*

Substances

  • Bronchodilator Agents
  • Muscarinic Antagonists
  • Tiotropium Bromide

Associated data

  • figshare/10.6084/m9.figshare.9334325