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