Introduction to Omalizumab

Omalizumab (brand name Xolair) is a recombinant DNA-derived humanized IgG1κ monoclonal antibody that selectively binds to human immunoglobulin E (IgE). It was first approved by the FDA in 2003 for the treatment of moderate to severe persistent asthma in patients with a positive skin test or in vitro reactivity to a perennial aeroallergen and symptoms that are inadequately controlled with inhaled corticosteroids.

Mechanism of Action

Omalizumab works by binding to free IgE in the bloodstream and interstitial fluid. This prevents IgE from binding to the high-affinity IgE receptor (FcεRI) on the surface of mast cells and basophils. As a result, it inhibits the release of inflammatory mediators such as histamine, leukotrienes, and cytokines when these cells encounter allergens.

Key points:

• Binds to the Cε3 domain of free IgE
• Forms small, biologically inert complexes with IgE
• Reduces free IgE levels in circulation by up to 99%
• Downregulates FcεRI expression on mast cells and basophils

Indications

Omalizumab is FDA-approved for the following indications:

1. Moderate to severe persistent asthma in patients 6 years and older with a positive skin test or in vitro reactivity to a perennial aeroallergen and symptoms that are inadequately controlled with inhaled corticosteroids
2. Chronic idiopathic urticaria in adults and adolescents 12 years and older who remain symptomatic despite H1 antihistamine treatment
3. Nasal polyps in adult patients 18 years and older with inadequate response to nasal corticosteroids

Off-label uses include:

• Allergic bronchopulmonary aspergillosis
• Atopic dermatitis
• Eosinophilic granulomatosis with polyangiitis

Dosage and Administration

Omalizumab is administered subcutaneously. The dosage varies based on the indication and patient characteristics:

For Asthma:

• Dose and frequency are determined by serum total IgE level (measured before the start of treatment) and body weight
• Doses range from 75 to 375 mg every 2 or 4 weeks
• Maximum dose is 375 mg every 2 weeks

For Chronic Idiopathic Urticaria:

• 300 mg every 4 weeks

For Nasal Polyps:

• 75 to 600 mg every 2 or 4 weeks, based on weight and serum IgE levels

Administration should be performed by a healthcare professional due to the risk of anaphylaxis.

Efficacy

Asthma:

• Reduces exacerbations by 38-50% in adults and adolescents
• Improves asthma-related quality of life
• Reduces use of inhaled corticosteroids and rescue medications
• In children, reduces exacerbations by 31% and improves asthma control

Chronic Idiopathic Urticaria:

• Significantly reduces itch severity and hive count
• Improves quality of life in patients with refractory urticaria

Nasal Polyps:

• Reduces nasal polyp size and improves nasal congestion
• Decreases need for surgery and systemic corticosteroid use

Side Effects

Common side effects (≥1% incidence) include:

• Injection site reactions (45%)
• Viral infections (23%)
• Upper respiratory tract infection (20%)
• Sinusitis (16%)
• Headache (15%)
• Pharyngitis (11%)

Serious side effects:

• Anaphylaxis (0.1-0.2%)
• Malignancy (slightly increased risk, causal relationship not established)
• Arterial thromboembolic events (rare)
• Serum sickness
• Eosinophilic conditions

Precautions and Monitoring

• Patients should be observed for at least 2 hours after the first 3 injections due to the risk of anaphylaxis
• Not to be used for acute asthma symptoms or status asthmaticus
• Gradual reduction of corticosteroids after initiation of omalizumab
• Monitor for parasitic (helminth) infections, especially in patients at high risk
• Discontinue if Churg-Strauss syndrome or hypereosinophilic syndrome develops
• Pregnancy Category B: Use only if clearly needed