Tiotropium Respimat Add-on Is Efficacious in Symptomatic Asthma, Independent of T2 Phenotype

J Allergy Clin Immunol Pract. May-Jun 2018;6(3):923-935.e9. doi: 10.1016/j.jaip.2017.08.037. Epub 2017 Nov 22.

Abstract

Background: Adding tiotropium to existing inhaled corticosteroid (ICS) maintenance therapy with or without a long-acting β2-agonist (LABA) has been shown to be beneficial in patients with symptomatic asthma.

Objective: To assess whether responses to tiotropium Respimat add-on therapy were influenced by patients' T2 status.

Methods: In this exploratory study, data from 4 phase III trials were analyzed: once-daily tiotropium 5 μg or placebo as add-on to ICS + LABA (PrimoTinA-asthma; 2 replicate trials; NCT00772538/NCT00776984; n = 912); once-daily tiotropium 5 μg or 2.5 μg, twice-daily salmeterol 50 μg, or placebo as add-on to ICS (MezzoTinA-asthma; 2 replicate trials; NCT01172808/NCT01172821; n = 2100). The prespecified efficacy outcomes of these studies have been reported previously. Here, further exploratory subgroup analyses were performed to study whether these coprimary end points were influenced by serum IgE levels, blood eosinophil counts, and clinician judgment of allergic asthma. In addition, for the continuous parameters, namely, IgE and blood eosinophils, their influence on the treatment effect was modeled over the whole range of values.

Results: Tiotropium was efficacious in improving peak FEV1 within 3 hours postdose and trough FEV1, independent of T2 status. Tiotropium significantly reduced the risk of severe asthma exacerbations and asthma worsening, independent of T2 phenotype; Cox regression modeling supported a beneficial effect of tiotropium on exacerbations, independent of IgE levels or eosinophil counts. Numerical improvements in the 7-question Asthma Control Questionnaire (ACQ-7) responder rate with tiotropium versus placebo were observed in T2high and T2low patients; logistic regression modeling provided further evidence for improvement in ACQ-7 responder rates with tiotropium, independent of IgE levels or eosinophil counts.

Conclusions: The results of our exploratory analyses suggest that the improvements seen with tiotropium Respimat as add-on to ICS ± LABA in patients with symptomatic asthma on lung function, exacerbation risk, and symptom control are independent of T2 phenotype.

Keywords: Allergy; Asthma; Eosinophil; IgE; Subgroup analysis; T2 status; Tiotropium Respimat.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adrenal Cortex Hormones / metabolism
  • Adrenergic beta-2 Receptor Agonists / therapeutic use*
  • Adult
  • Aged
  • Albuterol, Ipratropium Drug Combination / therapeutic use*
  • Asthma / drug therapy*
  • Bronchodilator Agents / therapeutic use*
  • Cytokines / metabolism
  • Drug Combinations
  • Drug Synergism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Salmeterol Xinafoate / therapeutic use*
  • Th2 Cells / immunology
  • Young Adult

Substances

  • Adrenal Cortex Hormones
  • Adrenergic beta-2 Receptor Agonists
  • Albuterol, Ipratropium Drug Combination
  • Bronchodilator Agents
  • Cytokines
  • Drug Combinations
  • Salmeterol Xinafoate

Associated data

  • ClinicalTrials.gov/NCT00772538
  • ClinicalTrials.gov/NCT00776984
  • ClinicalTrials.gov/NCT01172808
  • ClinicalTrials.gov/NCT01172821