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Background The D-prostanoid receptor and the chemoattractant receptor homologous molecule expressed on T H 2 cells (CRTH2) are implicated in asthma pathogenesis. AMG 853 is a potent, selective, orally bioavailable, small-molecule dual antagonist of human D-prostanoid and CRTH2. Objective We sought to determine the efficacy and safety of AMG 853 compared with placebo in patients with inadequately controlled asthma. Methods Adults with moderate-to-severe asthma were randomized to placebo; 5, 25, or 100 mg of oral AMG 853 twice daily; or 200 mg of AMG 853 once daily for 12 weeks. All patients continued their inhaled corticosteroids. Long-acting β-agonists were not allowed during the treatment period. Allowed concomitant medications included short-acting β-agonists and a systemic corticosteroid burst for asthma exacerbation. The primary end point was change in total Asthma Control Questionnaire score from baseline to week 12. Secondary and exploratory end points included FEV 1 , symptom scores, rescue short-acting β-agonist use, and exacerbations. Results Among treated patients, no effect over placebo (n = 79) was observed in mean changes in Asthma Control Questionnaire scores at 12 weeks (placebo, −0.492; range for AMG 853 groups [n = 317], −0.444 to −0.555). No significant differences between the active and placebo groups were observed for secondary end points. The most commonly reported adverse events were asthma, upper respiratory tract infection, and headache; 9 patients experienced serious adverse events, all of which were deemed unrelated to study treatment by the investigator. Conclusion AMG 853 as an add-on to inhaled corticosteroid therapy demonstrated no associated risks but was not effective at improving asthma symptoms or lung function in patients with inadequately controlled moderate-to-severe asthma.

Background Direct correlation of assessments of a validated composite measure such as the Asthma Control Questionnaire (ACQ) and risk of exacerbation has not been previously demonstrated in a randomized controlled trial. Objective To evaluate the ability of the ACQ score over time to predict risk of a future asthma exacerbation. Methods This analysis included data from a 12-week placebo-controlled trial (N = 292) of AMG 317, an IL-4 receptor α antagonist, in patients with moderate to severe atopic asthma. At baseline, patients had an ACQ score ≥1.5. Exacerbations were defined as requirement for systemic corticosteroids. A Cox proportional hazards model was used, with ACQ score as the time-dependent covariate. The analysis was repeated for individual components of the ACQ. Results Each 1-point increase in ACQ was associated with a 50% increased risk of exacerbation (hazard ratio, 1.50; 95% CI, 1.03-2.20) for the following 2-week period. Evaluation of individual ACQ components also demonstrated a similar trend, though each to a lesser degree than the full composite ACQ. Conclusion Although based on a retrospective analysis, with small number of exacerbations, these findings support the utility of the composite ACQ score measurement to predict risk of future exacerbation in clinical trials and clinical practice. The composite ACQ score measurement was found to be a better predictor of future risk than individual ACQ components.

T U E S D A Y 816 Effect of Inhaled Corticosteroids (ICS) Vs. Inhaled Corticosteroid with Long-Acting Beta2 Agonists (ICS/LABA) On Asthma Control: Results From National Asthma Survey Neetu Talreja, MD, Dennis K. Ledford, MD, FAAAAI, Richard F. Lockey, MD; Morsani College of Medicine University of South Florida and James A. Haley Veteran Hospital. RATIONALE: There is limited evidence for the comparative efficacy of ICS vs. ICS/LABA to treat asthma in children under 12 years. METHODS: Data from the 2003 National Asthma Survey were analyzed to compare asthma control in children (5 to 11 yrs) using ICS vs. ICS/LABA. Both short term (symptoms within last 2 weeks, day and night symptoms in last 30 days and use of systemic glucocorticoids in last 3 months) and long term (asthma exacerbation, emergency department visits, hospitalizations and activity limitations in the prior year) outcomes were compared. Demographics, availability of health insurance, indoor allergen exposure and asthma education were compared between the two groups. Asthma control in adult (18 to 44 years) and older population (>565 years) was also assessed for the same parameters. RESULTS: 134 children on ICS and 69 on ICS/LABA were identified. Baseline characteristics were similar in both groups. There were no differences in short and long term asthma outcomes between the two groups (p>0.05 for all outcome measures). Similar results were obtained with the adult and older population (p>0.05 for all outcome measures). ICS/LABAwas used for more than 6 months in 58% of children, 81% of adults and 46% of the older population. CONCLUSIONS: Asthma control in children using ICS vs. ICS/LABA was similar. So was asthma control using similar medications in the adult and older populations. LABA tolerance or the use of ICS/LABA in subjects with more severe asthma could explain these findings.