Predictors of response to tiotropium versus salmeterol in asthmatic adults

Stephen P. Peters, Eugene R. Bleecker, Susan J. Kunselman, Nikolina Icitovic, Wendy C. Moore, Rodolfo Pascual, Bill T. Ameredes, Homer A. Boushey, William J. Calhoun, Mario Castro, Reuben M. Cherniack, Timothy Craig, Loren C. Denlinger, Linda L. Engle, Emily A. Dimango, Elliot Israel, Monica Kraft, Stephen C. Lazarus, Robert F. Lemanske, Njira LugogoRichard J. Martin, Deborah A. Meyers, Joe Ramsdell, Christine A. Sorkness, E. Rand Sutherland, Stephen I. Wasserman, Michael J. Walter, Michael E. Wechsler, Vernon M. Chinchilli, Stanley J. Szefler

Research output: Contribution to journalArticlepeer-review

104 Scopus citations

Abstract

Background Tiotropium has activity as an asthma controller. However, predictors of a positive response to tiotropium have not been described. Objective We sought to describe individual and differential responses of asthmatic patients to salmeterol and tiotropium when added to an inhaled corticosteroid, as well as predictors of a positive clinical response. Methods Data from the double-blind, 3-way, crossover National Heart, Lung, and Blood Institute's Asthma Clinical Research Network's Tiotropium Bromide as an Alternative to Increased Inhaled Glucocorticoid in Patients Inadequately Controlled on a Lower Dose of Inhaled Corticosteroid (ClinicalTrials.gov number, NCT00565266) trial were analyzed for individual and differential treatment responses to salmeterol and tiotropium and predictors of a positive response to the end points FEV1, morning peak expiratory flow (PEF), and asthma control days (ACDs). Results Although approximately equal numbers of patients showed a differential response to salmeterol and tiotropium in terms of morning PEF (n = 90 and 78, respectively) and ACDs (n = 49 and 53, respectively), more showed a differential response to tiotropium for FEV1 (n = 104) than salmeterol (n = 62). An acute response to a short-acting bronchodilator, especially albuterol, predicted a positive clinical response to tiotropium for FEV1 (odds ratio, 4.08; 95% CI, 2.00-8.31; P <.001) and morning PEF (odds ratio, 2.12; 95% CI, 1.12-4.01; P = 0.021), as did a decreased FEV1/forced vital capacity ratio (FEV1 response increased 0.39% of baseline for every 1% decrease in FEV1/forced vital capacity ratio). Higher cholinergic tone was also a predictor, whereas ethnicity, sex, atopy, IgE level, sputum eosinophil count, fraction of exhaled nitric oxide, asthma duration, and body mass index were not. Conclusion Although these results require confirmation, predictors of a positive clinical response to tiotropium include a positive response to albuterol and airway obstruction, factors that could help identify appropriate patients for this therapy.

Original languageEnglish (US)
Pages (from-to)1068-1074.e1
JournalJournal of Allergy and Clinical Immunology
Volume132
Issue number5
DOIs
StatePublished - Nov 2013

Keywords

  • Asthma
  • predictor of response
  • responder analysis
  • salmeterol
  • tiotropium

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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