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Anti-IgE Use in AllergyAnti-IgE Use in Allergy
Pedro Giavina-BianchiPedro Giavina-Bianchi
Associate ProfessorAssociate ProfessorClinical Immunology and Allergy DepartmentClinical Immunology and Allergy Department
Medical School - University of São PauloMedical School - University of São Paulo
Chu and Drazen. Am J Respir Crit Care Med 2005;171:1202
The plant of ephedrine
1900 1920 1940 1960 1980 2000
Drug Treatment for Asthma
Epinephrine (injectable)
Epinephine (aerosol)
Ephedrine (oral)
Isoproterenol ( selective)
MDI devices
-2 selective
LABA
1950
Corticosteroids Leukotrienes modifiers
Hospitalization due to asthma in BrazilHospitalization due to asthma in Brazil
Year
No X 103
www.datasus.gov.br
ICS
ICS + LABA
Need for Improvements Need for Improvements
Adverse Effects
Partial relief of symptoms (severe cases)
Systemic disease
Interfere with the pathophysiology
Introduction of Omalizumab Introduction of Omalizumab
Austrália 2002
FDA 2003
EMEA 2005
Brasil2005
GINA2006
2200 FcRIIgE
IgE
1100
Plasma cell
Mast cell
3300
Anti-IgEAnti-IgE
Actions of Anti-IgEActions of Anti-IgE
Actions of Anti-IgEActions of Anti-IgE
4400
IgE
5500
FcRI
Macrophage Mast cell
FcRII
IgEAnti-IgEAnti-IgE
Outcome Parameter
Soler
(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 Omalizumab affects early and late asthmatic responseasthmatic response
OmalizumabOmalizumab
time (hours) n = 9time (hours) n = 90 1 2 3 4 5 6 7
65
75
85
95
105
FE
VF
EV
11
(% o
f b
ase
lin
e)
(% o
f b
ase
lin
e)
pp<0.05<0.05
PlaceboPlacebo
time (hours) n = 9time (hours) n = 90 1 2 3 4 5 6 7
65
75
85
95
105
Before treatmentBefore treatment after 56 days of treatmentafter 56 days of treatment
stimulationstimulation
Fahy JV. Am J Respir Crit Care Med 1997;155:1828-34
www.ginasthma.comwww.ginasthma.com
Expert Panel Report 3: Guidelines for the Diagnosis and Management of AsthmaNAEPP/NHLBI/NIH
Criteria for Indication Criteria for Indication
Severe asthma?
Patient > 6 years?
Multiple severe exacerbations?
Frequent daytime and nighttime symptoms?
Weight 20–150 Kg and total IgE 30-1300 IU/ml?
FEV1 % predicted < 80%?
Positive prick test or serum specific IgE?
OMALIZUMAB
NO
NO
NO
NO
NO
NO
NO
NO
NOT INDICATED
Not controlled with ICS + LABA?
YES
YES
YES
YES
YES
YES
YES
YES
Responders (60%)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 questionnairePEF: peak expiratory flow
Eosinophil
Th2 Immune ResponseTh2 Immune Response
B lymphocyteIgE
Perpetuation
IL4, IL5
Mast cell
Early Symptoms
IL5
T lymphocyte
IL4, IL13
Endothelium
VCAM1IL4
VLA4
Chemotaxis Factors
Late and Chronic Symptoms
Agondi RC. Allergy.2010;65:510-15
PerspectivesPerspectives
• Improvement of accessibility (cost)
• Setting phenotypes
• New indications
Omalizumab: Off-label IndicationsOmalizumab: 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
Saini S. J Allergy Clin Immunol 2011;128:567-73
Mea
n C
han
ge
Fro
m B
asel
ine
to W
eek
4 in
UA
S7
P < 0.001
P = 0.047
P = 0.16
Maurer M. J Allergy Clin Immunol 2011;128:202-9
FcRI
Mast cellCh
ang
e in
UA
S7
fro
m b
asel
ine
to
Wee
k 24
LS
M r
edu
ctio
n
P = 0.0089
Anti-IgE IgE
Adverse ReactionsAdverse Reactions
• Allergy
• Parasitoses
• Churg-Strauss Syndrome
AnaphylaxisAnaphylaxis
• 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
Cruz AA. Clin Exp Allergy 2007;37:197-207
Anti-IgE and ParasitosisAnti-IgE and Parasitosis
50%
41%
Omalizumab and Churg-Strauss SyndromeOmalizumab 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 RemarksFinal Remarks
Severe CasesSevere Cases
Cases not responsive to standard treatmentCases not responsive to standard treatment
Phenotype DependentPhenotype Dependent
Accessibility – Cost-BenefitAccessibility – Cost-Benefit
Risk-BenefitRisk-Benefit