Anti IgE Therapy

Anti IgE therapy (omalizumab) is a humanised monoclonal antibody given subcutaneously for allergic asthma, chronic spontaneous urticaria, nasal polyps and some food allergy. It reduces exacerbations in moderate to severe allergic asthma uncontrolled on inhaled therapy.

Mechanism. Omalizumab binds the C epsilon 3 domain of free IgE, lowering free IgE by over 90 percent and preventing binding to receptors on mast cells and basophils. Receptor numbers fall, mediator release falls and eosinophils fall.

Pharmacokinetics. Bioavailability is about 62 percent, peak at 7 to 8 days and half life about 26 days. Total IgE rises after starting because drug-IgE complexes accumulate, so on-treatment IgE must not be used to adjust dose.

Omalizumab. Dose 75 to 600 mg subcutaneously every 2 or 4 weeks, selected from the product table by the pre-treatment total IgE and body weight. Doses over 150 mg are split between injection sites. The allowed IgE range and weight range depend on the product label.

Chronic spontaneous urticaria. 150 mg or 300 mg every 4 weeks from 12 years.

Differences. Unlike anti IL-5 drugs, omalizumab needs proof of sensitisation to perennial aeroallergens, so it fits allergic asthma and asthma with other allergic disease.

Eligibility. Moderate to severe persistent allergic asthma with sensitisation to a perennial aeroallergen (skin test or specific IgE), total IgE within the label range, and uncontrolled disease on high dose inhaled corticosteroid with a long acting beta 2 agonist. Licensed from age 6 in most labels.

Response. Assess at 16 weeks, and continue if exacerbations, symptoms or oral corticosteroid use improve. Reassess at 12 months.

Administration. The first doses are given by a clinician with observation afterwards. Later doses may be self-injected after training, depending on the product.

Region. In patients at high risk of geohelminth infection, screen and treat before starting, because omalizumab may modestly raise the risk of infection.

Anaphylaxis. About 0.1 to 0.2 percent of patients, and it can occur after any dose, including after years of treatment. Boxed-warning level risk. Observe after injection, teach recognition of symptoms and give adrenaline for anaphylaxis.

Other adverse effects. Injection site reactions, headache, arthralgia, urticaria and, rarely, serum sickness and thrombocytopenia. Eosinophilic granulomatosis with polyangiitis can emerge when oral corticosteroids are reduced. A malignancy signal was not confirmed.

Interactions. None of clinical importance.

Monitoring. Baseline total IgE and weight, exacerbations, FEV1 and symptom scores. Do not remeasure IgE to adjust the dose.

Special groups. Pregnancy: registry data are reassuring, so continue if benefit. Breastfeeding: low oral absorption by the infant. Children: from 6 years. Older adults: no adjustment. Renal and hepatic impairment: no adjustment.

Referral and escalation. Failure to respond at 16 weeks needs a switch to a different biologic after specialist review.