title: Safety and tolerability of once-daily tiotropium Respimat(®) as add-on to at least inhaled corticosteroids in adult patients with symptomatic asthma: A pooled safety analysis.
abstract: Tiotropium, a long-acting anticholinergic bronchodilator, has demonstrated efficacy and safety as add-on therapy to inhaled corticosteroids (ICS), with or without other maintenance therapies, in patients with symptomatic asthma.
  
  
  
  To evaluate safety and tolerability of tiotropium delivered via the Respimat(®) device, compared with placebo, each as add-on to at least ICS therapy, in a pooled sample of adults with symptomatic asthma at different treatment steps.
  
  
  
  Data were pooled from seven Phase II and III, randomised, double-blind, parallel-group trials of 12-52 weeks' treatment duration, which investigated once-daily tiotropium Respimat(®) (5 μg, 2.5 μg) versus placebo as add-on to different background maintenance therapy including at least ICS. Adverse events (AEs) including serious AEs were assessed throughout treatment + 30 days after the last dose of trial medication.
  
  
  
  Of 3474 patients analysed, 2157 received tiotropium. The percentage of patients with AEs was comparable between treatment groups: tiotropium 5 μg, 60.8%; placebo 5 μg pool, 62.5%; tiotropium 2.5 μg, 57.1%; placebo 2.5 μg pool, 55.1%. Consistent with the disease profile, the most frequent AEs overall were asthma, decreased peak expiratory flow rate (both less frequent with tiotropium) and nasopharyngitis. Overall incidence of dry mouth, commonly associated with use of anticholinergics, was low: tiotropium 5 μg, 1.0%; placebo 5 μg pool, 0.5%; tiotropium 2.5 μg, 0.4%; placebo 2.5 μg pool, 0.5%. The percentage of cardiac disorder AEs was comparable between tiotropium and placebo: tiotropium 5 μg, 1.4%; placebo 5 μg pool, 1.4%; tiotropium 2.5 μg, 1.4%; placebo 2.5 μg pool, 1.1%. The proportions of patients with serious AEs were balanced across groups: tiotropium 5 μg, 4.0%; placebo 5 μg pool, 4.9%; tiotropium 2.5 μg, 2.0%; placebo 2.5 μg pool, 3.3%.
  
  
  
  Tiotropium Respimat(®) demonstrated safety and tolerability comparable with those of placebo, as add-on to at least ICS therapy, at different treatment steps in adults with symptomatic asthma.
authors: Odense University Hospital, University of Southern Denmark, Sdr Boulevard, DK 5000, Odense C, Denmark. Electronic address: ronald.dahl2@rsyd.dk.
authors: Ronald
authors: R
authors: Dahl
authors: TA Respiratory Diseases, Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Str. 173, 55216, Ingelheim, Germany.
authors: Michael
authors: M
authors: Engel
authors: Pulmonary Department and Adult Cystic Fibrosis Center, Paris Descartes University, Sorbonne Paris Cité, Cochin Hospital, 27 Rue du Fg St Jacques, 75014, Paris, France.
authors: Daniel
authors: D
authors: Dusser
authors: Royal Devon & Exeter Hospital, Barrack Rd, Exeter, Devon, EX2 5DW, UK.
authors: David
authors: D
authors: Halpin
authors: University of Groningen, Department of Pulmonary Medicine, and Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, Postbox 30.001, 9700 RB, Groningen, The Netherlands.
authors: Huib A M
authors: HAM
authors: Kerstjens
authors: Global Biometrics and Data Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorferstrasse 65, 88397, Biberach an der Riss, Germany.
authors: Liliana
authors: L
authors: Zaremba-Pechmann
authors: TA Respiratory Diseases, Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Str. 173, 55216, Ingelheim, Germany; Boehringer Ingelheim Pty Limited, Level 1, 78 Waterloo Rd, North Ryde, NSW 2113, Australia.
authors: Petra
authors: P
authors: Moroni-Zentgraf
authors: University of Wisconsin School of Medicine and Public Health, 600 Highland Ave, Madison, WI 53792, Wisconsin, USA.
authors: William W
authors: WW
authors: Busse
authors: Department of Medicine, University of Cape Town, Mowbray, 7700, Cape Town, South Africa.
authors: Eric D
authors: ED
authors: Bateman
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000627:therapeutic use; D000328:Adult; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000627:therapeutic use; D018680:Cholinergic Antagonists / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004361:Drug Tolerance / Q000502:physiology*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers / Q000592:standards* / Q000706:statistics & numerical data; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D000069447:Tiotropium Bromide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D000069447:Tiotropium Bromide
keywords: Asthma; Respimat(®); Safety; Tiotropium; Tolerability