Lessons learned from variation in response to therapy in clinical trials

In the past, we viewed lack of response to asthma medications as a rare event. Based on recent studies, we now expect significant variation in treatment response for all asthma medications. However, little information is available about methods to predict favorable treatment response. Research conducted in the National Heart, Lung, and Blood Institute's Asthma Clinical Research Network and Childhood Asthma Research and Education Network verified this variability in response to several long-term control medications, specifically inhaled corticosteroids and leukotriene receptor antagonists, in adults and children with mild-to-moderate persistent asthma. The networks also identified potential methods to use patients' characteristics, such as age and allergic status, and biomarkers, such as bronchodilator response, exhaled nitric oxide, and urinary leukotrienes, to help predict response to inhaled corticosteroids and leukotriene receptor antagonists and to determine which of the 2 treatments might be more effective in individual patients. This information now assists the clinician in personalizing asthma treatment at the time of initiating long-term control therapy.

Key words: Asthma, treatment response, inhaled corticosteroids, leukotriene receptor antagonists, leukotriene modifiers, β-adrenergic agonists

Abbreviations used: ACD, Asthma control day, ACRN, Asthma Clinical Research Network, BDP, Beclomethasone dipropionate, CARE, Childhood Asthma Research and Education, CLIC, Characterizing Response to Leukotriene Receptor Antagonist and Inhaled Corticosteroids, eNO, Exhaled nitric oxide, FP, Fluticasone propionate, ICS, Inhaled corticosteroid, LTRA, Leukotriene receptor antagonist, MDI, Metered-dose inhaler, MICE, Measuring Inhaled Corticosteroid Efficacy, NHLBI, National Heart, Lung, and Blood Institute, PACT, Pediatric Asthma Controller Trial, PEAK, Prevention of Asthma in Kids, PRICE, Predicting Response to Inhaled Corticosteroid Efficacy