The Predicting Response to Inhaled Corticosteroid Efficacy (PRICE) trial

Martin, Richard J.; Szefler, Stanley J.; King, Tonya S.; Kraft, Monica; Boushey, Homer A.; Chinchilli, Vernon M.; Craig, Timothy J.; DiMango, Emily A.; Deykin, Aaron; Fahy, John V.; Israel, Elliot; Lazarus, Stephen C.; Lemanske, Robert F.; Leone, Frank T.; Pesola, Gene R.; Peters, Stephen P.; Sorkness, Christine A.; Szwejbka, Lisa A.; Wechsler, Michael E.; for the National Heart, Lung, and Blood Institute's Asthma Clinical Research Center,

doi:10.1016/j.jaci.2006.10.035

« Previous Next »The Journal of Allergy and Clinical Immunology
Volume 119, Issue 1 , Pages 73-80, January 2007

The Predicting Response to Inhaled Corticosteroid Efficacy (PRICE) trial

Richard J. Martin, MD
- From National Jewish Medical and Research Center, Denver
- Reprint requests: Richard J. Martin, MD, National Jewish Medical and Research Center, 1400 Jackson Street, J206, Denver, CO 80206.
Stanley J. Szefler, MD
- From National Jewish Medical and Research Center, Denver
Tonya S. King, PhD
- Pennsylvania State University College of Medicine, Hershey
Monica Kraft, MD
- From National Jewish Medical and Research Center, Denver
Homer A. Boushey, MD
- University of California at San Francisco
Vernon M. Chinchilli, PhD
- Pennsylvania State University College of Medicine, Hershey
Timothy J. Craig, DO
- Pennsylvania State University College of Medicine, Hershey
Emily A. DiMango, MD
- Harlem Hospital Center and Columbia University, New York
Aaron Deykin, MD
- Brigham and Women's Hospital and Harvard Medical School, Boston
John V. Fahy, MD
- University of California at San Francisco
Elliot Israel, MD
- Brigham and Women's Hospital and Harvard Medical School, Boston
Stephen C. Lazarus, MD
- University of California at San Francisco
Robert F. Lemanske Jr., MD
- University of Wisconsin
Frank T. Leone, MD
- Thomas Jefferson University, Philadelphia
Gene R. Pesola, MD, MPH
- Harlem Hospital Center and Columbia University, New York
Stephen P. Peters, MD, PhD
- Thomas Jefferson University, Philadelphia
Christine A. Sorkness, PharmD
- University of Wisconsin
Lisa A. Szwejbka, MSPH
- Pennsylvania State University College of Medicine, Hershey
Michael E. Wechsler, MD
- Brigham and Women's Hospital and Harvard Medical School, Boston
for the National Heart, Lung, and Blood Institute's Asthma Clinical Research Center

Received 6 July 2006; received in revised form 25 October 2006; accepted 30 October 2006.

Denver, Colo, Hershey and Philadelphia, Pa, Boston, Mass, Madison, Wis, New York, NY, and San Francisco, Calif

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.

Key words: Inhaled corticosteroids, predicting response, therapy, characteristics, biomarkers

Abbreviations used: ACQ, Asthma Control Questionnaire, ACRN, Asthma Clinical Research Network, BHR, Bronchial hyperresponsiveness, FeNO, Fraction of exhaled nitric oxide, FVC, Forced vital capacity, ICS, Inhaled corticosteroid, NHLBI, National Heart, Lung, and Blood Institute, PEF, Peak expiratory flow

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.

PII: S0091-6749(06)02337-2

doi:10.1016/j.jaci.2006.10.035

« Previous Next »The Journal of Allergy and Clinical Immunology
Volume 119, Issue 1 , Pages 73-80, January 2007

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