Benralizumab

Benralizumab is a humanised monoclonal antibody against the interleukin-5 receptor alpha subunit, given subcutaneously every 8 weeks as add-on treatment for severe eosinophilic asthma and for eosinophilic granulomatosis with polyangiitis in some regions.

Classification. Anti-interleukin-5 receptor biologic, afucosylated IgG1 monoclonal antibody.

Mechanism. Binds the receptor on eosinophils and basophils and recruits natural killer cells, causing near-complete depletion of eosinophils by antibody-dependent cytotoxicity.

Pharmacokinetics. Subcutaneous bioavailability about 59%. Half-life about 15 to 20 days. Cleared by proteolytic catabolism.

Specialist, severe eosinophilic asthma, adults and adolescents from 12 years. Blood eosinophils of 300 cells/microlitre or more in the past 12 months with uncontrolled asthma despite high-dose inhaled corticosteroid with a LABA. Dose 30 mg subcutaneously every 4 weeks for the first 3 doses, then every 8 weeks. Assess response at 16 weeks.

Children 6 to 11 years, where licensed. 10 mg if under 35 kg and 30 mg if 35 kg or more, on the same schedule.

EGPA, adults, where licensed. 30 mg every 4 weeks.

Emergency. Not used.

Titration and loading. The first 3 doses 4 weeks apart serve as the loading phase. No weight-based titration in adults.

Contraindications. Hypersensitivity. Not for acute bronchospasm.

Serious adverse effects. Hypersensitivity reactions (including delayed reactions), worsening of helminth infection. There is no boxed warning.

Common adverse effects. Headache, pharyngitis, injection-site reactions, fever.

Interactions. None of clinical importance. Continue inhaled corticosteroid; taper oral corticosteroids gradually.

Common prescribing errors. Using every 8 weeks from the start without the first three 4-weekly doses. Abrupt oral corticosteroid withdrawal. Stopping the inhaled corticosteroid.

Special groups.

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

• Older adults: no adjustment.

• Kidney and liver impairment: no adjustment expected.

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

Formulations. Prefilled syringe and autoinjector 30 mg/mL.

Preparation. Remove from the refrigerator and allow about 30 minutes to reach room temperature. Do not shake. Do not use if cloudy. May remain out of the refrigerator for up to 14 days.

Administration. Subcutaneous into the thigh, abdomen or upper arm. Self-injection after training in suitable patients.

Baseline. Blood eosinophils, control score, oral corticosteroid dose, 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.

Stop and reduce rules. Stop for serious hypersensitivity. Stop if there is no clear benefit at 16 weeks. Therapeutic drug monitoring is not used.

Referral and escalation. Initiation is by a severe asthma specialist.