What are the indications and usage of Omalizumab (anti-IgE antibody) for patients with asthma or urticaria?

Omalizumab: Indications and Usage

Omalizumab is indicated as add-on therapy for patients aged 12 years and older with moderate-to-severe persistent allergic asthma inadequately controlled on high-dose inhaled corticosteroids plus long-acting beta-agonists, and for chronic spontaneous urticaria in patients who remain symptomatic despite H1-antihistamine treatment. 1, 2, 3

Primary Indications

Allergic Asthma

Omalizumab should be reserved for steps 5 and 6 of asthma management when symptoms remain uncontrolled despite optimized controller therapy. 4, 1

• Step 5: Consider omalizumab for patients on high-dose inhaled corticosteroids plus long-acting beta-agonists who have documented allergies and persistent symptoms 4
• Step 6: Consider omalizumab before initiating oral corticosteroids in patients with allergies, as part of maximal therapy with high-dose inhaled corticosteroids plus long-acting beta-agonists 4

Patient selection criteria:

• Age ≥12 years with moderate-to-severe persistent allergic asthma 2, 5
• Documented atopy with proven sensitivity to perennial aeroallergens 2, 5
• Inadequate control despite high-dose inhaled corticosteroids or high-dose ICS plus LABA therapy 2
• Elevated serum IgE levels within dosing range 1

Chronic Spontaneous Urticaria

• Omalizumab is indicated for chronic spontaneous urticaria in patients who remain symptomatic despite H1-antihistamine treatment 3, 6
• Evidence from randomized controlled trials demonstrates safety and efficacy in this population, with 139 patients enrolled across two trials showing benefit over placebo 6

IgE-Mediated Food Allergy

• Omalizumab is indicated for IgE-mediated food allergy, with dosing based on baseline IgE levels and body weight 3

Chronic Rhinosinusitis with Nasal Polyps

• Omalizumab is indicated for chronic rhinosinusitis with nasal polyps, administered every 2 or 4 weeks based on dosing tables 3

Mechanism of Action

Omalizumab binds to free circulating IgE at the Cε3 domain, preventing IgE from binding to high-affinity receptors (FcεRI) on mast cells, basophils, and dendritic cells. 5, 3

• This binding results in FcεRI down-regulation on effector cells, preventing cellular activation by allergens 3, 7
• In allergic asthmatics, omalizumab reduces blood and tissue eosinophils and decreases inflammatory mediators including IL-4, IL-5, and IL-13 3
• Serum free IgE levels decrease by >96% within 1 hour of the first dose using recommended doses 3
• Total IgE levels increase 3- to 5-fold due to formation of omalizumab:IgE complexes with slower elimination rates 3

Dosing and Administration

Dosage is determined by baseline serum total IgE levels (IU/mL) and body weight, administered subcutaneously every 2 or 4 weeks. 3, 7

• Typical doses range from 150-375 mg per injection 7
• The dosing formula approximates 0.016 mg/kg/IgE (IU/mL) per 4 weeks 7
• Mean elimination half-life is 26 days, allowing infrequent administration 7

Critical Safety Requirements

Omalizumab must be administered in a healthcare setting by providers trained to recognize and treat anaphylaxis. 1, 2

• FDA black-box warning: Anaphylaxis occurs in approximately 0.09-0.2% of patients and can occur after any dose 4, 2
• Patients must be observed for an appropriate period after each injection 1, 2
• All patients should be prescribed an epinephrine autoinjector and trained in its use 1, 2
• Common adverse events include injection site reactions, viral infections, upper respiratory tract infections, sinusitis, headache, and pharyngitis, occurring at similar rates to placebo 7, 8

Clinical Efficacy Evidence

Omalizumab reduces asthma exacerbations by 26-58% compared to placebo in patients with moderate-to-severe allergic asthma. 8

• The INNOVATE study in severe persistent asthma showed a 26% relative reduction in clinically significant exacerbations (after baseline adjustment) 8
• Studies in moderate-to-severe asthma demonstrated 41-58% relative reductions in mean exacerbations 8
• Approximately 40% of omalizumab recipients completely withdrew from ICS therapy while maintaining effective asthma control 7
• Significant improvements in asthma symptom scores, rescue medication use, and quality-of-life scores were consistently demonstrated 7, 8
• Benefits are maintained over 52 weeks of treatment in extension studies 7

Common Pitfalls to Avoid

Do not use omalizumab as monotherapy or before optimizing ICS/LABA therapy. 2

• Omalizumab is not indicated for non-allergic asthma 2, 5
• Do not use in children <12 years of age for asthma 2
• Do not use omalizumab to treat acute bronchospasm or status asthmaticus 2
• Ensure documented atopy with perennial aeroallergen sensitivity before initiating therapy 5

Adjunctive Use with Immunotherapy

Omalizumab pretreatment improves safety and tolerability of rush and cluster immunotherapy schedules. 4

• Omalizumab reduces systemic reactions during cluster immunotherapy from 26.2% to 13.5% 4
• Pretreatment with omalizumab for 9-16 weeks before rush immunotherapy results in a 5-fold decrease in anaphylaxis risk 4
• Combination therapy with immunotherapy improves symptom scores and asthma control compared to immunotherapy alone 4
• Omalizumab may enable VIT in patients with bee venom allergy who cannot otherwise tolerate it, and may improve tolerability in patients with mastocytosis 4