Tralokinumab interacts in the following cases:
No dose adjustment is needed in patients with renal impairment. Very limited data are available in patients with severe renal impairment.
No dose adjustment is needed in patients with hepatic impairment. Very limited data are available in patients with moderate or severe hepatic impairment.
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.
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.
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%).
Adverse reactions observed from clinical trials are presented in the following table 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.
List of adverse reactions:
| MedDRA System Organ Class | Frequency | Adverse reaction |
|---|---|---|
| Infections and infestations | Very common Common | Upper respiratory tract infections Conjunctivitis |
| Blood and lymphatic system disorders | Common | Eosinophilia |
| Eye disorders | Common Uncommon | Conjunctivitis allergic Keratitis |
| General disorders and administration site conditions | Common | Injection site reactions |
The long-term safety of tralokinumab was assessed in 2 monotherapy studies up to 52 weeks, and in a combination study with topical corticosteroids up to 32 weeks. The long-term safety of tralokinumab is further assessed in an open-label extension study (ECZTEND) for up to 5 years of treatment in adults and adolescents with moderate-to-severe AD (atopic dermatitis) receiving 300 mg of tralokinumab every two weeks (Q2W). Interim safety data up to 39 months were generally consistent with the safety profile observed up to week 16 in the pool of 5 adult studies.
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.
The rate of conjunctivitis in the interim safety data from the long-term open-label extension study (ECZTEND) was 3.37 events/100 patient years of exposure, compared with 22.0 events/100 patient years of exposure in the initial 16 weeks 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.
The rate of keratitis in the interim safety data from the long-term open-label extension study (ECZTEND) was 0.15 events/100 patient years of exposure, compared with 1.7 events/100 patient years of exposure in the initial 16 weeks treatment period.
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 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. The rate of eczema herpeticum in the initial 16 weeks treatment period was 1.2 events/100 years of exposure. The rate of eczema herpeticum in the interim safety data from the long-term open-label extension study (ECZTEND) was 0.60 events/100 years of exposure.
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.
The ADA incidence for subjects who received tralokinumab up to 52 weeks was 4.6%; 0.9% had persistent ADA and 1.0% had neutralising antibodies.
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.
The rate of injection site reactions in the interim safety data from the long-term open-label extension study (ECZTEND) was 5.8 events/100 patient years of exposure, compared with 51.5 events/100 patient years of exposure in the initial 16 weeks treatment period.
The safety of tralokinumab was assessed in patients 12 to 17 years of age (adolescents) with moderate-to-severe atopic dermatitis in a monotherapy study of 289 adolescents (ECZTRA 6) and in a long-term open-label extension study (ECZTEND) including 127 adolescents transferred from ECZTRA 6. The safety profile of tralokinumab in these patients followed through the initial treatment period of 16 weeks and the long-term treatment period of 52 weeks (ECZTRA 6), as well as in the interim safety data from the long-term open-label extension study up to 21 months (ECZTEND) were similar to the safety profile from studies in adults. However, a lower frequency of subjects with conjunctivitis was observed with tralokinumab in adolescents (1.0%) than in adults (5.4%), and, unlike in adults, the frequency of conjunctivitis allergic was similar for tralokinumab and placebo in adolescent patients.
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