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

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

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

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

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

9. Belliveau e Lahoz. Dis Manage Health Outcomes 2007;15
Outcome Parameter
Soler
(2001)
Busse
Holgate
(2004)
Ayres
Humbert
(2005)
Exacerbations Rate  
No of patients with an exacerbation NA
ICS dose requirements
No of patients with discontinuation of ICS therapy
Symptom scores
Nocturnal symptom scores
Rescue medication requirements
Morning PEF rates 
FEV1
 / 
 = increase;  = unchenged;  = decrease; NA = not assessed
Belliveau e Lahoz. Dis Manage Health Outcomes 2007;15

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

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

13. Criteria for Indication
YES
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 IU/ml? NO
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. Late and Chronic Symptoms
Th2 Immune Response
B lymphocyte
IgE
Mast cell
Early Symptoms
Perpetuation
IL4, IL5
IL4, IL13
Chemotaxis Factors
T lymphocyte
IL5
Eosinophil
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. Omalizumab: Off-label Indications
Allergic Rhinitis
Chronic Urticaria
Atopic Dermatitis
Food Allergy
Associado a Imunoterapia
ABPA
Mastocytosis
Sinusitis/Polyposis
Latex Allergy
Drug Allergy
Idiopatic Anaphylaxis
Eosinofilic Diseases

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

21. Change in UAS7 from baseline to Week 24 LSM reduction
FceRI
Mast cell
Anti-IgE
IgE
Change in UAS7 from baseline to Week 24 LSM reduction
P =
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:

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