Predictors of response to tiotropium versus salmeterol in asthmatic adults

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.

Keywords: ACD; ACRN; Asthma; Asthma Clinical Research Network; Asthma control day; FVC; Forced vital capacity; HFA; Hydrofluoroalkane; ICS; Inhaled corticosteroid; LABA; LAMA; Long-acting muscarinic antagonist; Long-acting β-agonist; NHLBI; National Heart, Lung, and Blood Institute; OR; Odds ratio; PEF; Peak expiratory flow; TALC; 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; predictor of response; responder analysis; salmeterol; tiotropium.

Figure 1

Acute responses (defined as FEV₁ % change) of patients in the TALC trial to 4 puffs of albuterol and 4 puffs of ipratropium, administered on different days, after bronchodilator drug withholds.

Figure 2

Individual (Figures 2A, 2B, 2C) patient responses to salmeterol and tiotropium in terms of AM PEF (Figure 2A), FEV₁ (Figure 2B), and Asthma Control Days (Figure 2C).

Figure 2

Individual (Figures 2A, 2B, 2C) patient responses to salmeterol and tiotropium in terms of AM PEF (Figure 2A), FEV₁ (Figure 2B), and Asthma Control Days (Figure 2C).

Figure 2

Individual (Figures 2A, 2B, 2C) patient responses to salmeterol and tiotropium in terms of AM PEF (Figure 2A), FEV₁ (Figure 2B), and Asthma Control Days (Figure 2C).

Figure 3

Relationship between the acute response (defined as FEV₁ % change) to short-acting bronchodilator and the clinical effect of long-acting bronchodilator. Figure 3A acute response to 4 puffs of albuterol and the clinical response to salmeterol in terms of FEV₁. Figure 3B acute response to 4 puffs of ipratropium and the clinical response to tiotropium in terms of FEV₁.

Figure 3

Relationship between the acute response (defined as FEV₁ % change) to short-acting bronchodilator and the clinical effect of long-acting bronchodilator. Figure 3A acute response to 4 puffs of albuterol and the clinical response to salmeterol in terms of FEV₁. Figure 3B acute response to 4 puffs of ipratropium and the clinical response to tiotropium in terms of FEV₁.