Dupilumab

Dupilumab is a human monoclonal antibody against the interleukin-4 receptor alpha subunit, blocking interleukin-4 and interleukin-13 signalling. It is given subcutaneously for moderate to severe type 2 asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, eosinophilic oesophagitis, prurigo nodularis and, in some regions, eosinophilic COPD.

Classification. Anti-interleukin-4 receptor alpha biologic, IgG4 monoclonal antibody.

Mechanism. Blocks interleukin-4 and interleukin-13 receptor signalling, reducing type 2 inflammation, IgE and airway hyperresponsiveness.

Pharmacokinetics. Subcutaneous bioavailability 61 to 64%. Non-linear clearance at low concentrations. Time to steady state 16 weeks. Half-life 2 to 4 weeks at usual doses.

Specialist, moderate to severe type 2 asthma, adults and adolescents from 12 years. Eosinophilic phenotype (blood eosinophils 150 cells/microlitre or more) or oral corticosteroid-dependent asthma, uncontrolled on high-dose inhaled corticosteroid with a LABA.

• 400 mg loading then 200 mg every 2 weeks.

• 600 mg loading then 300 mg every 2 weeks for oral corticosteroid-dependent asthma or for coexisting moderate to severe atopic dermatitis.

• Loading doses are given as 2 injections at separate sites.

Children 6 to 11 years with asthma. 100 mg every 2 weeks for 15 to under 30 kg; 200 mg every 2 weeks for 30 kg or more.

Atopic dermatitis, adults. 600 mg loading then 300 mg every 2 weeks. Dosing in children and adolescents is by weight, with a 4-weekly schedule at lower weights.

Chronic rhinosinusitis with nasal polyps, adults. 300 mg every 2 weeks.

Eosinophilic oesophagitis. 300 mg every week, for adults and children of 40 kg or more where licensed.

COPD with eosinophilic phenotype, where licensed. 300 mg every 2 weeks.

Emergency. Not used.

Titration. Doses are fixed and continued for at least 16 weeks before judging response. No dose changes by laboratory result.

Contraindications. Hypersensitivity. Not for acute bronchospasm.

Serious adverse effects. Hypereosinophilia with vasculitis resembling eosinophilic granulomatosis with polyangiitis (especially as oral corticosteroids are reduced), conjunctivitis and keratitis, hypersensitivity including serum sickness, helminth infection. There is no boxed warning.

Common adverse effects. Injection-site reactions, conjunctivitis, oral herpes, head and neck facial erythema, transient blood eosinophilia, arthralgia.

Interactions. Avoid live vaccines. No important drug interactions. Continue inhaled corticosteroid and LABA.

Common prescribing errors. Giving only half a loading dose. Using 200 mg instead of 300 mg when a 600 mg loading dose is called for. Abrupt oral corticosteroid withdrawal. Missing eye symptoms.

Special groups.

• Pregnancy: IgG crosses the placenta; limited data, so use only if needed. Breastfeeding: probably compatible.

• Children from 6 years: dosing is by weight.

• Older adults: no adjustment.

• Kidney and liver impairment: no adjustment expected.

• East Africa: treat helminth infection before starting. Availability is very limited.

Formulations. Prefilled pen and syringe 200 mg/1.14 mL and 300 mg/2 mL.

Preparation. Remove from the refrigerator and allow 30 minutes (200 mg) to 45 minutes (300 mg) to reach room temperature. Do not shake.

Administration. Subcutaneous into the thigh or abdomen, or upper arm if given by a caregiver. Rotate sites. Self-injection after training.

Baseline. Blood eosinophils, control score, oral corticosteroid dose, eye history, stool examination in helminth-endemic areas.

Monitoring. Exacerbations, control score, oral corticosteroid dose and lung function at 16 weeks and each 6 to 12 months. Eosinophils and symptoms of vasculitis. Eye symptoms at each review.

Stop and reduce rules. Stop for serious hypersensitivity or vasculitis features. Review for keratitis if eye symptoms persist. Therapeutic drug monitoring is not used.

Referral and escalation. Initiation is by a specialist. Refer urgently for eye pain or visual change, or vasculitis features.