Tralokinumab

There is limited amount of data from the use of tralokinumab in pregnant women.

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.

As a precautionary measure, it is preferable to avoid the use of tralokinumab during pregnancy.

It is unknown whether tralokinumab is excreted in human milk or absorbed systemically after ingestion. A decision must be made whether to discontinue breast-feeding or to discontinue tralokinumab therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility

Animal studies did not show any effects on male and female reproductive organs and on sperm count, motility and morphology.

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

Summary of the safety profile

The most common adverse reactions are upper respiratory tract infections (23.4%; mainly reported as common cold), injection site reactions (7.2%), conjunctivitis (5.4%) and conjunctivitis allergic (2.0%).

Tabulated list of adverse reactions

In a pool of 5 randomised, double-blind, placebo-controlled studies in patients with moderate to severe atopic dermatitis (ECZTRA 1, ECZTRA 2, and ECZTRA 3, a dose ranging trial and a vaccine-response study), 1,991 subjects were treated with subcutaneous injections of tralokinumab, with or without concomitant topical corticosteroids. A total of 807 patients were treated with tralokinumab for at least 1 year.

Listed in Table 1 are adverse reactions observed from clinical trials presented by system organ class and frequency, using the following categories: 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). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. The frequencies are based on the initial treatment period of up to 16 weeks in the pool of 5 studies in the atopic dermatitis population.

Table 1. List of adverse reactions:

The long-term safety of tralokinumab was assessed in the 2 monotherapy studies up to 52 weeks and in 1 combination study with topical corticosteroids up to 32 weeks. The safety profile of tralokinumab through week 52 and week 32 respectively was consistent with the safety profile observed up to week 16.

Description of selected adverse reactions

Conjunctivitis and related events

Conjunctivitis occurred more frequently in atopic dermatitis patients who received tralokinumab (5.4%) compared to placebo (1.9%) in the initial treatment period of up to 16 weeks in the pool of 5 studies. Conjunctivitis was reported at a higher frequency in patients with severe atopic dermatitis compared to subjects with moderate atopic dermatitis in both the tralokinumab group (6.0 vs 3.3%; initial treatment period) and placebo group (2.2 vs 0.8%; initial treatment period). Most patients recovered or were recovering during the treatment period.

Keratitis was reported in 0.5% of subjects treated with tralokinumab during the initial treatment period. Of these, half were classified as keratoconjunctivitis, all were non-serious and mild or moderate in severity, and none led to treatment discontinuation.

Eosinophilia

Adverse reactions of eosinophilia were reported in 1.3% of patients treated with tralokinumab and 0.3% of patients treated with placebo during the initial treatment period of up to 16 weeks in the pool of 5 studies. Tralokinumab-treated patients had a greater mean initial increase from baseline in eosinophil count compared to patients treated with placebo. Eosinophilia (≥5,000 cells/mcL) was measured in 1.2% of tralokinumab-treated patients and 0.3% of placebo-treated patients in the initial treatment period. However, the increase in the tralokinumab-treated patients was transient, and mean eosinophil counts returned to baseline during continued treatment. The safety profile for subjects with eosinophilia was comparable to the safety profile for all subjects.

Eczema Herpeticum

Eczema herpeticum was reported in 0.3% of the subjects treated with tralokinumab and in 1.5% of subjects in the placebo group, in the initial treatment period of up to 16 weeks in the pool of 5 studies in atopic dermatitis. Across all treatment periods in the pool of 5 studies, all eczema herpeticum events reported in the tralokinumab group were non-serious, none were severe, and a single event led to permanent discontinuation of treatment.

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity with tralokinumab.

Anti-drug-antibody (ADA) responses were not associated with any impact on tralokinumab exposure, safety, or efficacy.

In ECZTRA 1, ECZTRA 2, ECZTRA 3, and the vaccine-response study, the incidence of ADA up to 16 weeks was 1.4% for patients treated with tralokinumab and 1.3% for patients treated with placebo; neutralising antibodies were seen in 0.1% of patients treated with tralokinumab and 0.2% of patients treated with placebo.

Across all trial periods, the ADA incidence for subjects who received tralokinumab was 4.6%; 0.9% had persistent ADA and 1.0% had neutralising antibodies.

Injection site reactions

Injection site reactions (including pain and redness) occurred more frequently in patients who received tralokinumab (7.2%) compared to placebo (3.0%) in the initial treatment period of up to 16 weeks in the pool of 5 studies. Across all treatment periods in the 5 studies in atopic dermatitis, the vast majority (99%) of injection site reactions were mild or moderate in severity, and few patients (<1%) discontinued tralokinumab treatment. Most injections site reactions reported had a short duration with approximately 76% of the events resolving within 1 to 5 days.