Transcript OmalizumabCancunHandouts

Anti-IgE Use in Allergy
Pedro Giavina-Bianchi
Associate Professor
Clinical Immunology and Allergy Department
Medical School - University of São Paulo
The plant of ephedrine
Chu and Drazen. Am J Respir Crit Care Med 2005;171:1202
Drug Treatment for Asthma
Epinephrine (injectable)
Corticosteroids
Epinephine (aerosol)
Leukotrienes modifiers
Ephedrine (oral)
Isoproterenol (b selective)
MDI devices
b-2 selective
LABA
1900
1920
1940
1950
1960
1980
2000
Hospitalization due to asthma in Brazil
ICS
No X 103
www.datasus.gov.br
ICS + LABA
Year
Need for Improvements
Adverse Effects
Partial relief of symptoms (severe cases)
Systemic disease
Interfere with the pathophysiology
Introduction of Omalizumab
Austrália
2002
FDA
2003
EMEA
2005
Brasil
2005
GINA
2006
Actions of Anti-IgE
Plasma cell
Anti-IgE
30
IgE
10
IgE
20 FceRI
Mast cell
Actions of Anti-IgE
Anti-IgE
IgE
Anti-IgE
50
FceRII
Macrophage
IgE
40
FceRI
Mast cell
Soler
Outcome Parameter (2001)
Busse
(2001)
Holgate
(2004)
Ayres
(2004)
Humbert
(2005)
Exacerbations Rate





No of patients with an
exacerbation


NA

NA
ICS dose requirements




NA
No of patients with
discontinuation of ICS
therapy
NA


NA
NA
Symptom scores





Nocturnal symptom
scores

NA
NA
NA
NA
Rescue medication
requirements





Morning PEF rates

NA

NA

FEV1


/


 = increase;  = unchenged;  = decrease; NA = not assessed
Belliveau e Lahoz. Dis Manage Health Outcomes 2007;15
Omalizumab affects early and late
asthmatic response
stimulation
stimulation
(% of baseline)
FEV1
Omalizumab
Placebo
105
105
95
95
p<0.05
85
85
75
75
65
65
0
1
3
4
2
5
time (hours) n = 9
6
Before treatment
7
0
1
3
4
2
5
time (hours) n = 9
6
7
after 56 days of treatment
Fahy JV. Am J Respir Crit Care Med 1997;155:1828-34
www.ginasthma.com
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
NAEPP/NHLBI/NIH
Criteria for Indication
YES
Severe asthma?
YES
Patient > 6 years?
YES
YES
NO
NO
Not controlled with ICS + LABA?
Multiple severe exacerbations?
NO
NO
YES
Frequent daytime and nighttime symptoms?
YES
FEV1 % predicted < 80%?
YES
Positive prick test or serum specific IgE?
YES
Weight 20–150 Kg and total IgE 30-1300 IU/ml? NO
OMALIZUMAB
NO
NO
NO
NOT INDICATED
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
Th2 Immune Response
IgE
B lymphocyte
Mast cell
Early
Symptoms
IL4, IL13
Perpetuation
Chemotaxis
Factors
IL4, IL5
T lymphocyte
Eosinophil
IL5
VLA4
IL4
VCAM1
Endothelium
Late and Chronic
Symptoms
Agondi RC. Allergy.2010;65:510-15
Perspectives
• Improvement of accessibility (cost)
• Setting phenotypes
• New indications
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
Open label study
12 Patients
• 7 Complete response
• 4 Partial response
• 1 No response
Kaplan AP. J Allergy Clin Immunol 2008;122:569-73
Mean Change From Baseline to Week 4 in UAS7
Placebo
OMA 75 mg OMA 300 mg OMA 600 mg
0.00
-5.00
-10.00
P = 0.16
-15.00
P = 0.047
-20.00
P < 0.001
-25.00
Saini S. J Allergy Clin Immunol 2011;128:567-73
Change in UAS7 from baseline to
Week 24 LSM reduction
Placebo
Omalizumab
Anti-IgE
0
IgE
-5
FceRI
-10
-15
P = 0.0089
-20
Mast cell
Maurer M. J Allergy Clin Immunol 2011;128:202-9
Adverse Reactions
• Allergy
• Parasitoses
• Churg-Strauss Syndrome
Anaphylaxis
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•
•
•
•
•
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
Anti-IgE and Parasitosis
41%
50%
Cruz AA. Clin Exp Allergy 2007;37:197-207
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
Final Remarks
Severe Cases
Cases not responsive to standard treatment
Phenotype Dependent
Accessibility – Cost-Benefit
Risk-Benefit