Tezepelumab

Tezepelumab is a human monoclonal antibody against thymic stromal lymphopoietin (TSLP), an upstream epithelial cytokine. It is given subcutaneously every 4 weeks for severe asthma with no phenotype restriction, and in some regions for chronic rhinosinusitis with nasal polyps.

Classification. Anti-TSLP biologic, IgG2 monoclonal antibody.

Mechanism. Neutralises TSLP, lowering eosinophils, IgE, FeNO and interleukin-5 and interleukin-13 signalling at the top of the inflammatory cascade.

Pharmacokinetics. Subcutaneous bioavailability about 77%. Half-life about 26 days. Cleared by proteolytic catabolism.

Specialist, severe asthma, adults and adolescents from 12 years. Add-on when asthma remains uncontrolled on high-dose inhaled corticosteroid with a LABA and another controller, regardless of eosinophil count or allergic status. Dose is 210 mg subcutaneously every 4 weeks. Assess response at 16 weeks and then each year.

Chronic rhinosinusitis with nasal polyps, adults, where licensed. 210 mg every 4 weeks.

Emergency. Not used.

Titration and loading. No loading dose, no titration, no weight adjustment.

Contraindications. Hypersensitivity. Not for acute bronchospasm.

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

Common adverse effects. Pharyngitis, arthralgia, back pain, injection-site reactions.

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

Common prescribing errors. Stopping the inhaled corticosteroid. Abrupt oral corticosteroid withdrawal. Using it for acute attacks.

Special groups.

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

• Children: not licensed under 12 years.

• 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 210 mg/1.91 mL.

Preparation. Remove from the refrigerator and allow the pen or syringe to reach room temperature, up to about an hour. Do not shake. Do not use if cloudy or discoloured.

Administration. Subcutaneous into the thigh or abdomen, or upper arm if given by a caregiver. Self-injection after training in patients 12 years and over, with supervision for adolescents.

Baseline. Control score, exacerbation count, eosinophils and FeNO if available, 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.