Omalizumab

Omalizumab is a humanised monoclonal anti-IgE antibody given by subcutaneous injection as add-on treatment for severe persistent allergic asthma, chronic spontaneous urticaria, chronic rhinosinusitis with nasal polyps and, in some regions, IgE-mediated food allergy.

Classification. Anti-IgE biologic, humanised IgG1 monoclonal antibody.

Mechanism. Binds free IgE, preventing its attachment to high-affinity receptors on mast cells and basophils, which lowers receptor expression and allergen-triggered mediator release.

Pharmacokinetics. Subcutaneous bioavailability about 62%. Half-life about 26 days. Cleared by the reticuloendothelial system. Total serum IgE rises after starting because it is bound to the drug, and cannot be used to guide dosing while on treatment.

Specialist, severe persistent allergic asthma, adults and children from 6 years. Inadequately controlled on high-dose inhaled corticosteroid with a LABA, with a positive perennial aeroallergen test or sensitisation and baseline total IgE in the labelled range (generally 30 to 700 IU/mL, extended to 1500 IU/mL in some regions).

• Dose is 75 to 600 mg subcutaneously every 2 or 4 weeks, set from a dosing table using baseline total IgE and body weight. The 4-weekly dose is about 0.016 mg/kg for each IU/mL of IgE.

• Maximum 600 mg every 2 weeks.

• Assess response at 16 weeks. Stop if there is no clear improvement in exacerbations, control or oral corticosteroid need.

Chronic spontaneous urticaria, adults and adolescents from 12 years. 150 mg or 300 mg every 4 weeks, regardless of IgE or weight. Review the dose and need regularly.

Chronic rhinosinusitis with nasal polyps, adults. 75 to 600 mg every 2 or 4 weeks from the dosing table, as add-on to an intranasal corticosteroid.

IgE-mediated food allergy, where licensed. 75 to 600 mg every 2 or 4 weeks by baseline IgE and weight, to reduce reactions after accidental exposure. Strict allergen avoidance continues.

Emergency. Not used.

Titration. Recalculate the dose when body weight changes substantially. Do not use new IgE results while on treatment. If treatment stops for a year or more, re-measure IgE to restart.

Boxed-warning-level risk. Anaphylaxis (about 0.2% of patients), which can occur after any dose, even after years of treatment. Give in a clinical setting with resuscitation capability, observe after injection (usually 2 hours for the first 3 doses and 30 minutes after), and provide adrenaline auto-injector training.

Contraindications. Severe hypersensitivity to omalizumab. Not for acute bronchospasm or status asthmaticus.

Serious adverse effects. Anaphylaxis, serum sickness-like reaction, eosinophilic granulomatosis with polyangiitis unmasked as corticosteroid doses fall, thrombocytopenia (rare), parasitic infection in high-risk patients.

Common adverse effects. Injection-site reactions, headache, upper respiratory infection, sinusitis, arthralgia.

Interactions. None of major clinical importance. Continue inhaled corticosteroid and LABA.

Common prescribing errors. Using the dose of a different indication. Using IgE levels taken on treatment to adjust the dose. Stopping inhaled corticosteroid. Giving to patients with no allergen sensitisation.

Special groups.

• Pregnancy: IgG crosses the placenta; registry data are reassuring and treatment may continue if needed. Breastfeeding: IgG enters milk in small amounts; probably compatible.

• Children from 6 years: use the same dosing table.

• Older adults: no adjustment.

• Kidney and liver impairment: not studied; no adjustment is expected.

• East Africa: in areas with high geohelminth burden, screen and treat intestinal helminth infection before starting, because blocking IgE may weaken the response to helminths. Availability and funding are very limited and use is confined to specialist centres.

Formulations. Prefilled syringes 75, 150 and 300 mg (single-dose), and lyophilised powder 150 mg vials in some regions.

Preparation. Vials are reconstituted with 1.4 mL sterile water for injection, giving 125 mg/mL. Dissolution takes 15 to 20 minutes. Gently swirl, do not shake. Store refrigerated at 2 to 8 degrees Celsius.

Administration. Subcutaneous injection into the thigh or abdomen. Divide doses over 150 mg between sites when using vials. Rotate sites.

Baseline. Total IgE, perennial allergen sensitisation, weight, eosinophils, stool examination where helminths are endemic.

Monitoring. Control score, exacerbations, oral corticosteroid use and lung function at 16 weeks and then each 4 to 6 months. Observe after each of the early doses.

Stop and reduce rules. Stop after any anaphylaxis. Stop at 16 weeks if no clear benefit. Therapeutic drug monitoring is not used.

Referral and escalation. Initiation is by a severe asthma or allergy specialist. Refer urgently for any systemic allergic reaction.