Tezepelumab

The use of live attenuated vaccines should be avoided in patients receiving tezepelumab.

Abrupt discontinuation of corticosteroids after initiation of therapy is not recommended. Reduction in corticosteroid doses, if appropriate, should be gradual and performed under the supervision of a physician.

Blocking thymic stromal lymphopoietin (TSLP) may theoretically increase the risk of serious infections. In placebo-controlled studies, no increase in serious infections was observed with tezepelumab.

Patients with pre-existing serious infections should be treated before initiating therapy with tezepelumab. If patients develop a serious infection while receiving tezepelumab treatment, therapy with tezepelumab should be discontinued until the serious infection resolves.

There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of tezepelumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.

Human IgG antibodies, such as tezepelumab, are transported across the placenta barrier; therefore, tezepelumab may be transmitted from the mother to the developing foetus.

As a precautionary measure, it is preferable to avoid the use of tezepelumab during pregnancy unless the expected benefit to the pregnant mother is greater than any possible risk to the foetus.

It is unknown whether tezepelumab is excreted in human milk. Human IgGs are known to be excreted in breast milk during the first few days after birth, which decreases to low concentrations soon afterwards; consequently, a risk to the breast-fed child cannot be excluded during this short period.

For this specific period, a decision should be made whether to discontinue/abstain from tezepelumab therapy, taking into account the benefit of breast-feeding to the child and the benefit of therapy to the woman.

Afterwards, tezepelumab could be used during breast-feeding if clinically needed.

Fertility

There are no fertility data in humans. Animal studies showed no adverse effects of tezepelumab treatment on fertility.

Tezepelumab has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

The most commonly reported adverse reactions during treatment are arthralgia (3.8%) and pharyngitis (4.1%).

Tabulated list of adverse reactions

In clinical studies in patients with severe asthma, a total of 665 patients received at least one dose of tezepelumab in trials of 52 weeks duration.

The frequency of adverse reactions is defined using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); and not known (cannot be estimated from available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

List of adverse reactions:

^a Pharyngitis was defined by the following grouped preferred terms: pharyngitis, pharyngitis bacterial, pharyngitis streptococcal and viral pharyngitis.
^b Rash was defined by the following grouped preferred terms: rash, rash pruritic, rash erythematous, rash maculo-papular, rash macular.
^c See ‘Description of selected adverse reactions’.

Description of selected adverse reactions

Injection site reactions

In the pooled safety data from PATHWAY and NAVIGATOR, injection site reactions (e.g. injection site erythema, injection site swelling, injection site pain) occurred at a rate of 3.8% in patients treated with tezepelumab 210 mg subcutaneous every 4 weeks (Q4W).

Paediatric population

A total of 82 adolescents aged 12 to 17 with severe, uncontrolled asthma were enrolled in the 52 week Phase 3 NAVIGATOR study. The safety profile in adolescents was generally similar to the overall study population.