The Predicting Response to Inhaled Corticosteroid Efficacy (PRICE) trial

Abstract

Background: Although guidelines recommend anti-inflammatory therapy for persistent asthma, recent studies suggest that 25% to 35% of patients with asthma may not improve lung function with inhaled corticosteroids.

Objective: To evaluate potential biomarkers of predicting short-term (6-week) response to inhaled corticosteroid with subsequent evaluation of responders and nonresponders to asthma control over a longer interval (16 additional weeks).

Methods: Eighty-three subjects with asthma off steroid were enrolled in this multicenter study. Biomarkers and asthma characteristics were evaluated as predictors of inhaled corticosteroid response over a 6-week trial for changes in FEV(1) and methacholine PC(20). After this, an additional 4-month trial evaluated asthma control.

Results: Although multiple baseline predictors had significant correlations with improvements for short-term inhaled steroid success, the only strong correlations (r >or= +/- 0.6) were albuterol reversibility (r = 0.83; P < .001), FEV(1)/forced vital capacity (r = -0.75; P < .001), and FEV(1) % predicted (r = -0.71; P < .001). Dividing the subjects in the short-term inhaled steroid trial into responders (>5% FEV(1) improvement) and nonresponders (<or=5%) determined the longer-term need for steroids. For the nonresponders, asthma control remained unchanged whether inhaled corticosteroids were continued or were substituted with a placebo (P = .99). The good short-term responders maintained asthma control longer-term only if maintained on inhaled steroids (P = .007).

Conclusion: The short-term response to inhaled corticosteroids with regard to FEV(1) improvement predicts long-term asthma control.

Clinical implications: The decision to use long-term inhaled steroids could be based on a short-term trial. Different therapeutic strategies would need to be established for nonresponders.

Figure 1

Demonstrates the protocol time line with the different interventions. Stratification is based on the 6-week inhaled corticosteroid (ICS) response: poor, intermediate, and good. Baseline and repeat measurements included the biomarkers of β₂-agonist response, FeNO, and induced sputum eosinophils. Duration of asthma diagnosis was initially obtained. The “mini” Asthma Control Questionnaire was measured prior to the 16-week trial and once every month during the 16 weeks.

Figure 2

The FEV₁ distribution response to inhaled corticosteroid over the short term 6-week trial. Bars represent 5% increments in FEV₁ response.

Figure 3

Induced sputum characteristics stratified by inhaled corticosteroid response (post 6-week trial, prior to long term trial). Horizontal lines represent 25^th, 50^th, and 75^th percentile.

Figure 4

Asthma control as measured by the asthma control questionnaire (ACQ) over the 16-week inhaled corticosteroid (ICS) or placebo (PBO) continuation trial. The groups are categorized based on the FEV₁ results of the prior 6-week ICS trial: Non-responders ≤ 5% improvement to ICS; Responders > 5% improvement on ICS. Only significant within group difference occurred between PBO and ICS responder groups, p=0.007. A lower ACQ score equates to better asthma control. PBO = placebo; ICS = inhaled corticosteroid.