1. 내과 R2 이지영

2. INTRODUCTION  Asthma  Allergic airway inflammation,Th2-weighted process  Biomarkers  Phenotypic distinctions  Development of personalized medicine  Predict responses to therapy  IgE  IL-4, IL-5, and IL-13 from Th2-type CD4+ cells  IgE class  Levels of cytokines are low & cannot be measured  IgE, not been predictive of response to anti-IgE therapy

3. INTRODUCTION  Three biomarkers  Fractional exhaled nitric oxide (FENO)  From IL-13  Clinical use by American Thoracic Society (ATS)  Peripheral blood eosinophils  Distinct phenotype (eosinophilic asthma)  Serum periostin  From airway epithelial cells in response to IL-13

4. INTRODUCTION  Omalizumab (Xolair)  Recombinant humanizedmonoclonal antibody that selectively binds to free IgE  Moderate-to-severe persistent allergic asthma (IgE-mediated), inadequately controlled with inhaled corticosteroids (ICS)  EXTRA study  Potential of 3 biomarkers to predictors  Therapeutic benefit of omalizumab

5. Method HighLow FeNO ≥19.5 ppb<19.5 Peripheral blood eosinophil count ≥260/ul<260/ul Serum periostin levels ≥50ng/ml<50ng/ml  12–75 years of age & history of severe persistent allergic asthma for more than 1 year  Randomized to omalizumab or placebo for 48wks (+ high-dose ICS and LABA, with or without controller medications)  Cut off

6. Method  Treatment effect  48-week treatment period  Exacerbations: Requiring systemic corticosteroids for >3 d or increase of >20 mg in the average daily OCS dose  Secondary efficacy endpoints  Asthma symptom score  Albuterol use  Asthma quality of life questionnaire (AQLQ)  % predicted FEV1

7. Results

9.  Evaluation of patterns of treatment effect for varying levels of each biomarker  Time to first protocol-defined exacerbation

10. Results  Evaluation of secondary endpoints.

11. Results  Safety  Treatment-emergent AEs was similar in the biomarker-low and biomarker-high subgroups

12. Conclusion Overall population of premenopausal women  The difference in exacerbation frequency between omalizumab and placebo was greatest in the three high-biomarker subgroups, probably associated with the greater risk for exacerbations in high subgroups.  Additional studies are required to explore the value of these biomarkers in clinical practice.