Anti-IgE Use in Allergy

1. Anti-IgE Use in Allergy Pedro Giavina-Bianchi Associate Professor Clinical Immunology and Allergy Department Medical School - University of São Paulo

2. The plant of ephedrine Chu and Drazen. Am J Respir Crit Care Med 2005;171:1202

3. Drug Treatment for Asthma Epinephrine (injectable) Corticosteroids Leukotrienes modifiers Epinephine (aerosol) Ephedrine (oral) Isoproterenol (b selective) MDI devices b-2 selective LABA 1900 1920 1940 1950 1960 1980 2000

4. Hospitalization due to asthma in Brazil ICS No X 103 ICS + LABA Year www.datasus.gov.br

5. Need for Improvements • Adverse Effects • Partial relief of symptoms(severe cases) • Systemic disease • Interfere with the pathophysiology

6. Introduction of Omalizumab Austrália 2002 EMEA 2005 Brasil 2005 GINA 2006 FDA 2003

7. IgE 30 10 FceRI 20 Actions of Anti-IgE Plasma cell Anti-IgE IgE Mast cell

8. Actions of Anti-IgE IgE IgE Anti-IgE Anti-IgE 40 50 FceRI FceRII Mast cell Macrophage

9.  = increase;  = unchenged;  = decrease; NA = not assessed Belliveau e Lahoz. Dis Manage Health Outcomes 2007;15

10. 105 105 95 95 85 85 75 75 65 65 1 3 4 6 1 3 4 6 0 2 5 7 0 2 5 7 Omalizumab affects early and late asthmatic response stimulation stimulation Omalizumab Placebo FEV1 (% of baseline) p<0.05 time (hours) n = 9 time (hours) n = 9 after 56 days of treatment Beforetreatment Fahy JV. Am J Respir Crit Care Med 1997;155:1828-34

11. www.ginasthma.com

12. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma NAEPP/NHLBI/NIH

13. Criteria for Indication Severe asthma? NO YES Patient > 6 years? NO YES Not controlled with ICS + LABA? NO YES Multiple severe exacerbations? NO YES Frequent daytime and nighttime symptoms? NO YES FEV1 % predicted < 80%? NO YES Positive prick test or serum specific IgE? NO YES Weight 20–150 Kg and total IgE 30-1300 IU/ml? NO YES OMALIZUMAB NOT INDICATED

14. Responders (60%) 16 weeks Evaluation of treatment response in UK • Physician’s assessment • Main assessment: ACT* (>2) e Mini-AQLQ* (>0.5) • Assessment of Suport: PEF* e Exacerbacions ACT: asthma control test Mini-AQLQ: asthma quality of life questionnaire PEF: peak expiratory flow

15. Th2 Immune Response IgE B lymphocyte Mast cell Early Symptoms Perpetuation IL4, IL5 IL4, IL13 Chemotaxis Factors T lymphocyte Eosinophil IL5 VLA4 Late and Chronic Symptoms IL4 VCAM1 Endothelium

16. Agondi RC. Allergy.2010;65:510-15

17. Perspectives • Improvement of accessibility (cost) • Setting phenotypes • New indications

18. Allergic Rhinitis Chronic Urticaria Atopic Dermatitis Food Allergy Associado a Imunoterapia ABPA Mastocytosis Sinusitis/Polyposis Latex Allergy Drug Allergy Idiopatic Anaphylaxis Eosinofilic Diseases Omalizumab: Off-label Indications

19. Open label study 12 Patients • 7 Complete response • 4 Partial response • 1 No response Kaplan AP. J Allergy Clin Immunol 2008;122:569-73

20. P = 0.16 Mean Change From Baseline to Week 4 in UAS7 P = 0.047 P < 0.001 Saini S. J Allergy Clin Immunol 2011;128:567-73

21. Anti-IgE IgE FceRI Change in UAS7 from baseline to Week 24 LSM reduction P = 0.0089 Mast cell Maurer M. J Allergy Clin Immunol 2011;128:202-9

22. Adverse Reactions • Allergy • Parasitoses • Churg-Strauss Syndrome

23. Anaphylaxis Prevalence < 0.2% Informed Consent Guindance on anaphylaxis Dispositivos de auto-inoculação de epinefrina Clinical assessment Observation for 2 hours for the first 3 injections / other injections 30’ (75% of cases) Cox L. J Allergy Clin Immunol 2007;120:1373-7

24. Anti-IgE and Parasitosis 41% 50% Cruz AA. Clin Exp Allergy 2007;37:197-207

25. Omalizumab and Churg-Strauss Syndrome Winchester DE. N Engl J Med 2006;355 Giavina-Bianchi P. J Allergy Clin Immunol 2007;119 Giavina-Bianchi P. Int Arch Allergy Immunol 2007;144

26. Final Remarks Severe Cases Cases not responsive to standard treatment Phenotype Dependent Accessibility – Cost-Benefit Risk-Benefit