Anti IL4 and IL13 Pathway Therapy

Anti IL4 and IL13 therapy (dupilumab) blocks the IL-4 receptor alpha chain, which inhibits signalling by both IL-4 and IL-13. It treats type 2 asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, eosinophilic oesophagitis and prurigo nodularis, and COPD with eosinophilia.

Mechanism. Blockade reduces IgE class switching, eosinophil recruitment, mucus production, airway hyperresponsiveness and epithelial barrier injury. FeNO and total IgE fall, and blood eosinophils rise transiently.

Pharmacokinetics. Absorption after subcutaneous injection is slow, with a half life of about 3 to 4 weeks at the doses used. Clearance is by target-mediated and proteolytic routes.

Dupilumab in asthma. 400 mg subcutaneously as a loading dose, then 200 mg every 2 weeks, from 12 years. For oral corticosteroid-dependent asthma or comorbid moderate to severe atopic dermatitis, 600 mg loading then 300 mg every 2 weeks. Children 6 to 11 years: 100 mg every 2 weeks under 30 kg and 200 mg every 2 weeks at 30 kg or more.

Dupilumab in COPD. 300 mg every 2 weeks when blood eosinophils are 300 cells/microlitre or more with exacerbations on triple therapy.

Differences. Unlike anti IL-5 drugs, dupilumab treats several type 2 conditions together and works at lower eosinophil counts and in oral corticosteroid-dependent disease regardless of count.

Eligibility. Severe asthma with blood eosinophils of 150 cells/microlitre or more, or FeNO of 25 ppb or more, or oral corticosteroid dependence. Best response is with higher eosinophils and higher FeNO. Use is cautious when eosinophils exceed 1500 cells/microlitre, and other causes of eosinophilia are excluded first.

Best candidates. Patients with asthma and atopic dermatitis, nasal polyps or eosinophilic oesophagitis.

Response. Assess at 4 months. Eosinophil count is not used to monitor response because it rises on treatment.

Region. Treat helminth infection before starting. Cost and supply limit use in many settings.

Adverse effects. Injection site reactions, conjunctivitis and keratitis (more with atopic dermatitis), arthralgia, headache and facial erythema.

Eosinophilia. Transient blood eosinophilia is common, and rarely progresses to eosinophilic pneumonia or eosinophilic granulomatosis with polyangiitis, especially when oral corticosteroid is reduced. Check eosinophils and assess when counts exceed 1500 cells/microlitre or symptoms suggest vasculitis.

Infections. Helminth infection should be treated before starting. Live vaccines are avoided.

Hypersensitivity. Rare anaphylaxis. Observe at first dose.

Monitoring. Exacerbations, oral corticosteroid dose, FEV1, symptoms, eye symptoms, and eosinophil count after oral corticosteroid reduction.

Special groups. Pregnancy: limited data, use if benefit outweighs risk. Breastfeeding: IgG poorly absorbed by the infant. Children: from 6 years. Older adults and organ impairment: no adjustment.

Referral and escalation. Prescribing needs a specialist. Eye pain or loss of vision needs ophthalmology review, and new vasculitic features need urgent assessment.