Omalizumab (Anti-IgE)

Mechanism

Mechanism of action

Severe allergic asthma is mediated by the binding of IgE to high affinity receptors (FcεRI) located on the surface of mast cells and basophils. Omalizumab interferes at this point in the biological cascade:

1. Neutralization of circulating free IgE: Omalizumab specifically binds to the Cε3 constant domain of the free IgE molecule. This blocks the portion of IgE that interacts with the FcεRI receptor, preventing its anchoring to effector cells.
2. No drug-induced degranulation: Since omalizumab cannot bind to IgE that is already bound to mast cell or basophil receptors, it lacks the risk of inducing cellular degranulation or cross-anaphylaxis during its systemic binding.
3. Downregulation of FcεRI receptors: The drastic reduction in the concentration of free IgE in plasma induces an adaptive decrease in the expression of high affinity FcεRI receptors on the membrane of mast cells, basophils and dendritic cells, persistently reducing sensitivity to future allergens.

Mechanism of Deactivation of Dendritic Cells

The reduction of the FcεRI receptor in mucosal dendritic cells significantly reduces their capacity for antigen presentation to new exogenous allergens. This reduces the stimulation of naïve T helper lymphocytes and the consequent production of Th2 cytokines, achieving an attenuating effect on chronic bronchial remodeling of the airway.

Pharmacokinetics

Pharmacokinetics

• Rout of administration: Exclusively deep subcutaneous (SC).
• Absorption: Slow absorption with a bioavailability of 62%. Maximum plasma concentration (C_max) achieved between 7 and 8 days after injection.
• Distribution and Metabolism: Nonspecific proteolytic catabolism mediated by the reticuloendothelial system after the formation of stable oligomeric Omalizumab-IgE complexes. It does not undergo renal filtration or classic hepatic metabolic clearance of microsomal origin.
• Half-life: Approximately 26 days in asthmatic patients.

Indicators and dose

Approved clinical indications

• Severe persistent allergic asthma: Adjunctive treatment in adults, adolescents and children over 6 years of age with a documented diagnosis of IgE-mediated allergic asthma who present with recurrent severe exacerbations despite treatment with maximum doses of ICS/LABA.
• Refractory chronic spontaneous urticaria (CSU): Complementary treatment in patients with insufficient response to H1 antihistamines at quadruple doses.
• Severe refractory nasal polyposis: In adults in combination with nasal corticosteroids.

Dosage and Clinical Adjustment

The dosage of omalizumab in asthma and nasal polyposis is not fixed; It is necessarily calculated individually according to two baseline parameters:

1. Basal serum level of Total immunoglobulin E (IU/mL) before the start of treatment.
2. Body weight (kg) of the patient.

These variables are entered into standardized dosing tables to administer between 75 mg and 600 mg subcutaneously every 2 weeks or every 4 weeks.

In Chronic Spontaneous Urticaria: The dose is fixed, 300 mg subcutaneously every 4 weeks, regardless of basal IgE levels.

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Adverse effects (ADRs)

• Injection site reactions: Local erythema, inflammation, pruritus and transient pain (≈ 12%).
• Systemic anaphylaxis: A rare but potentially serious adverse effect (< 0.1%). It characteristically occurs in the first 2 hours after the first doses. *Safety rule:* The drug must be administered exclusively in medical centers with complete cardiopulmonary resuscitation equipment, and the patient must remain under close medical observation for a minimum period of 2 hours.
• Parasitic infections (Helminthiasis): Since IgE mediates the natural immune defense against helminths, patients in endemic areas have a slightly increased risk of infection and should be monitored.