OMALIZUMAB

(PG1/2)

MD 2 | PBL Case: #10, Francis DiAnza Sony Ton | 11/24/2010

Drug: Omalizumab—DNA-derived humanized monoclonal IgG1 antibody Context:

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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 cellbound IgE @ antigen binding site  FcRI cross-linking  cell activation*  early phase-response (i.e. degranulation of histamine, heparin) and late phaseresponse (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 asthma, not controlled by inhaled corticosteroids for people aged 12 years and older
*Recommended for severe asthma (Step 5 or 6 care)

Side Effects:     Eosinophilic disorder*
*Systemic eosinopilia and vasculitis similar to Churg-Strauss syndrome; associated with reduced glucocorticoid therapy

Serum sickness*

Adverse Drug Interactions: may interact with warfarin and increase prothrombin times Contraindications: drug hypersensitivity Considerations:  

*Symptoms include arthritis/arthralgia, rash, fever, and lymphadenopathy after 1 to 5 days of injection

Anaphylaxis Thrombocytopenia

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.
1. 2. 3. 4. Basic & Clinical Pharmacology, 11e: (AccessMedicine) Goodman & Gilman, 11e (AccessMedicine) EpocratesOnline: Omalizumab MicroMEDEX: Omalizumab

References:

Francis DiAnza Sony Ton | 11/24/2010 Omalizumab and IgE complexes. hexamers are the largest complexes formed. Copyright. Anti-IgEtherapy.OMALIZUMAB (PG2/2) MD 2 | PBL Case: #10. (From Brownell J and Casale TB. with permission. 24: 551– 568.) . Immunol Allergy Clin North Am 2004. Omalizumab binds to the CH3 domain of the IgE molecule typically forming trimers. Elsevier.