Mepolizumab

Mepolizumab is a humanised monoclonal antibody against interleukin-5, given subcutaneously as add-on treatment for severe eosinophilic asthma, chronic rhinosinusitis with nasal polyps, eosinophilic granulomatosis with polyangiitis (EGPA), hypereosinophilic syndrome and, in some regions, eosinophilic COPD.

Classification. Anti-interleukin-5 biologic, humanised IgG1 monoclonal antibody.

Mechanism. Binds circulating interleukin-5, blocking its action on the eosinophil receptor and lowering blood and tissue eosinophils.

Pharmacokinetics. Subcutaneous bioavailability about 80%. Half-life 16 to 22 days. Cleared by proteolytic catabolism.

Specialist, severe eosinophilic asthma, adults and children from 6 years. Add-on when asthma remains uncontrolled on high-dose inhaled corticosteroid with a LABA and another controller, with blood eosinophils of 150 cells/microlitre or more at starting or 300 cells/microlitre or more in the past 12 months.

• Adults and adolescents from 12 years: 100 mg subcutaneously every 4 weeks.

• Children 6 to 11 years: 40 mg subcutaneously every 4 weeks.

• Assess response at 16 weeks and then each year.

Chronic rhinosinusitis with nasal polyps, adults. 100 mg every 4 weeks.

EGPA and hypereosinophilic syndrome, adults. 300 mg every 4 weeks, given as three 100 mg injections.

COPD with eosinophilic phenotype, where licensed. 100 mg every 4 weeks for patients with frequent exacerbations despite triple inhaled therapy and blood eosinophils of 300 cells/microlitre or more.

Emergency. Not used.

Titration and loading. No loading dose. Doses are fixed; no weight adjustment.

Contraindications. Hypersensitivity to mepolizumab. Not for acute bronchospasm.

Serious adverse effects. Hypersensitivity reactions (usually within hours, delayed reactions are possible), herpes zoster, opportunistic infection, worsening of helminth infection. There is no boxed warning.

Common adverse effects. Headache, injection-site reactions, back pain, fatigue, nasopharyngitis.

Interactions. None of clinical importance. Continue inhaled corticosteroid; taper oral corticosteroids only gradually and under supervision.

Common prescribing errors. Stopping the inhaled corticosteroid. Abrupt oral corticosteroid withdrawal. Using it in non-eosinophilic asthma. Not treating helminth infection first.

Special groups.

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

• Children 6 to 11 years: 40 mg dose.

• Older adults: no adjustment.

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

• East Africa: treat existing helminth infection before starting, because eosinophil suppression may reduce defence against helminths. Consider vaccination against herpes zoster where available. Availability is very limited.

Formulations. Prefilled pen and syringe 100 mg/mL; lyophilised powder 100 mg vial.

Preparation. Vials are reconstituted with 1.2 mL sterile water for injection, giving 100 mg/mL; allow up to 5 minutes to dissolve, swirl gently, and use within 8 hours. Prefilled devices are allowed to reach room temperature for about 30 minutes.

Administration. Subcutaneous into the thigh, abdomen or upper arm. Self-injection is allowed after training in patients over 12 years.

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

Monitoring. Exacerbations, control score, oral corticosteroid dose, lung function and eosinophils at 16 weeks and then 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. Refer for vasculitis features when corticosteroids are tapered.