MD 2 | PBL Case: #10, Francis

OMALIZUMAB (PG1/2) DiAnza

Sony Ton | 11/24/2010

Drug: Omalizumab—DNA-derived humanized monoclonal IgG1 antibody

Context:
 Atopic asthma (i.e. extrinsic) is a common form of asthma and is characterized by Type 1
hypersensitivity, which involves IgE-mediated inflammatory responses.
 The IgE’s Fc region (i.e. heavy-chain, constant region, non-antigen binding site) binds with
high affinity to the Fc-epsilon receptor I (FcRI), which is expressed on the cell surfaces of
inflammatory cells including mast cells and basophils.
 Activation phase: Interaction between antigen and cell-
bound IgE @ antigen binding site  FcRI cross-linking
 cell activation*  early phase-response (i.e.
degranulation of histamine, heparin) and late phase-
response (i.e. synthesis of eicosanoids)
*IgE-mediated activation is extremely efficacious, requiring antigen
to interact with only a small fraction of the bound IgE to evoke a
half-maximal response.
 Examples of Type 1 hypersensitivity: asthma, allergic
rhinitis, anaphylaxis
Mechanism of Action: formation of IgE–Omalizumab
complexes
 Major: The antibody’s antigen-biding site neutralizes
the free IgE in the serum* by binding IgE’s Fc region to
form high-affinity IgE–Omalizumab complexes 
prevents the IgE from binding to FcRI, thereby blocking allergen-induced cell activation.
*Omalizumab, at recommended dose, will reduce free IgE by more than 95%
 Decr. FcRI expression on inflammatory cells,

Indications: IgE-mediated allergic Side Effects:

asthma, not controlled by inhaled
corticosteroids for people aged 12
years and older
*Recommended for severe asthma (Step 5
or 6 care)
Adverse Drug Interactions: may
interact with warfarin and increase
prothrombin times
Contraindications: drug
hypersensitivity
 Eosinophilic disorder*
*Systemic eosinopilia and vasculitis similar to Churg-Strauss
syndrome; associated with reduced glucocorticoid therapy
 Serum sickness*
*Symptoms include arthritis/arthralgia, rash, fever, and
lymphadenopathy after 1 to 5 days of injection
 Anaphylaxis
 Thrombocytopenia

Considerations:
 Omalizumab is injected sub-Q every 2 or 4 weeks. The dosage is determined by the patient’s
IgE level before first treatment and patient’s body weight
 Omalizumab has been used in the treatment of other allergic disorders, such as nasal allergy
and food allergy, but large-scale clinical trials are limited to asthma.
References:
1. Basic & Clinical Pharmacology, 11e: (AccessMedicine)
2. Goodman & Gilman, 11e (AccessMedicine)
3. EpocratesOnline: Omalizumab
4. MicroMEDEX: Omalizumab
 MD 2 | PBL Case: #10, Francis
OMALIZUMAB (PG2/2) DiAnza
Sony Ton | 11/24/2010

Omalizumab and IgE complexes. Omalizumab binds to the CH3 domain of the IgE molecule
typically forming trimers; hexamers are the largest complexes formed.
(From Brownell J and Casale TB. Anti-IgEtherapy. Immunol Allergy Clin North Am 2004; 24: 551–
568, with permission. Copyright, Elsevier.)