Asthma diagnosis and treatment
The Predicting Response to Inhaled Corticosteroid Efficacy (PRICE) trial

https://doi.org/10.1016/j.jaci.2006.10.035Get rights and content

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 FEV1 and methacholine PC20. 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 ≥ ± 0.6) were albuterol reversibility (r = 0.83; P < .001), FEV1/forced vital capacity (r = −0.75; P < .001), and FEV1 % predicted (r = −0.71; P < .001). Dividing the subjects in the short-term inhaled steroid trial into responders (>5% FEV1 improvement) and nonresponders (≤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 FEV1 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.

Section snippets

Study population

Inclusion criteria for study subjects were individuals with asthma between 18 and 55 years of age with a baseline FEV1 55% to 85% predicted and a methacholine PC20 ≤12 mg/mL. Because FEV1 reversibility was an outcome variable, this was not used as an inclusion criterion. No ICS or systemic corticosteroids were allowed for at least 4 weeks before enrollment. No smoking was allowed for 1 year before enrollment, and cumulative exposure was less than 10 pack-years. Other exclusion criteria included

Study population

A total of 83 subjects were enrolled, with 36 men and 47 women. Thirty-eight minority (African American and Latino) individuals were enrolled. These subjects came from surrounding communities of the individual ACRN centers and not specifically from patients seen at these testing referral centers. Of the 83 enrolled subjects, 72 completed the initial 6-week trial. The reasons for dropout are described below. The baseline descriptive characteristics of the 72 subjects are shown in Table I.

Discussion

This ACRN protocol prospectively evaluated biomarkers and characteristics associated with ICS response and, in addition, determined whether a short-term response or lack of response to ICS predicted longer-term asthma control. With regard to biomarkers and characteristics as predictors of ICS response, only the response to a short-acting β2-agonist (albuterol), low percentage predicted FEV1, and FEV1/FVC ratio had a strong (r ≥± 0.6) correlation with response. Of potential importance was the

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Supported by US National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI)-HL04285, HL051810, HL051823, HL051831, HL051834, HL051843, HL051845, and HL056443.

Disclosure of potential conflict of interest: R. J. Martin has consulting arrangements with Ivax, Merck, GlaxoSmithKline, Schering, Novartis, Genentech, Altana, and Sanofi-Aventis; has received grant support from GlaxoSmithKline and Altana; and is on the speakers' bureau for Ivax, Merck, Novartis, and Genentech. S. J. Szefler has consulting arrangements with AstraZeneca, GlaxoSmithKline, Aventis, Genentech, and Merck and has received grant support from the NIH, the NHLBI, the National Institute of Allergy and Infectious Diseases (NIAID), and Ross Pharmaceuticals. M. Kraft has consulting arrangements with Genentech, GlaxoSmithKline, Merck, Boehringer Ingelheim, Asthmatx, and TEVA; has received grant support from GlaxoSmithKline, Genentech, Altana, and Asthmatx; and is on the speakers' bureau for GlaxoSmithKline, Genentech, Merck, Schering, Sepraco, and Pfizer. H. A. Boushey has consulting arrangements with Watermark Research Protein Design Lab, Altana, and Sumitomo; has received grant support from GlaxoSmithKline; and has received honoraria from Merck, Novartis, Sanofi-Aventis, and Genentech. V. M. Chinchilli has received grant support from the Asthma Clinical Research Network, the NIH, and the Childhood Asthma Research and Education Network. T. J. Craig has consulting arrangements with Alcon, Johnson and Johnson, and TEVA; has received grant support from GlaxoSmithKline, Merck, Sanofi-Aventis, Boehringer Ingelheim, Dyax, ZLB, LEV, Pharming, and AstraZeneca; and is on the speakers' bureau for Merck, Pfizer, AstraZeneca, Boehringer Ingelheim, Dyax, ZLB, LEV, Pharming, and Sanofi-Aventis. E. A. DiMango has consulting arrangements with AstraZeneca and has received grant support from Novartis and Genentech. A. Deykin has consulting arrangements with Aerocrine; owns stock in Biogen Idec; is employed by Biogen Idec; has received grant support from Merck; and is on the speakers' bureau for Merck. J. V. Fahy has consulting arrangements with Arriva Pharmaceuticals, Abgenix, Oxagen, and Zymogenetics and has received grant support from the NHLBI, the California Tobacco Research Program, and the University of California, San Francisco Sandler Asthma Program. E. Israel has consulting arrangements with Asthmatx, Critical Therapeutics, Genentech, Merck, Novartis, Protein Design Lab, Schering Plough, and Wyeth Research; has received grant support from Asthmatx, Boehringer Ingelheim, Centocor, Genentech, GlaxoSmithKline, and Merck; and is on the speakers' bureau for Genentech and Merck. R. F. Lemanske, Jr, has consulting arrangements with Merck, GlaxoSmithKline, AstraZeneca, Aventis, and Novartis; has pending US patent application serial number 11/176026, published as US 2006-0069074 on March 30, 2006; has received grant support from the NHLBI and the NIAID; and is on the speakers' bureau for Merck, GlaxoSmithKline, AstraZeneca, and Aventis. F. T. Leone has received grant support from the NIH, the American Lung Association, the Pennsylvania Department of Health, and the Philadelphia Department of Health and is on the speakers' bureau for Pfizer. S. P. Peters has consulting arrangements with the NIH, Adelphi, the American Thoracic Society, AstraZeneca, Discovery, Ception Therapeutics, Genentech, Novartis, Omnicare, the Rad Foundation, Respiratory Medicine, Respiratory Research, and Sanofi-Aventis; has received grant support from the NIH, the NHLBI, the American Lung Association, Abaris, AstraZeneca, Altana, Boehringer Ingelheim, Centocor, Genentech, GlaxoSmithKline, Novartis, Pfizer, and Wyeth; and has participated in physician education programs that included speakers' bureau and Continuing Medical Education programs for the American College of Chest Physicians, the American Thoracic Society, the American Academy of Allergy, Asthma, & Immunology, the American College of Allergy, Asthma and Immunology, AstraZeneca, Merck, Genentech, Novartis, Practicome, Pri-Med, Respiratory and Allergic Disease, and UpToDate. C. A. Sorkness has consulting arrangements with AstraZeneca and GlaxoSmithKline; has received grant support from GlaxoSmithKline; and is on the speakers' bureau for GlaxoSmithKline. M. E. Wechsler has consulting arrangements with Merck, Genentech, Novartis, and Pfizer and is on the speakers' bureau for Merck, GlaxoSmithKline, and Novartis. The rest of the authors have declared that they have no conflict of interest.

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