Tralokinumab

Tralokinumab is a human IgG4 monoclonal antibody that, unlike dupilumab, binds specifically to the interleukin-13 cytokine (IL-13). IL-13 plays an essential role in the pathogenesis of atopic dermatitis and bronchial asthma. Blockade of IL-13 prevents interaction with the receptor and prevents subsequent downstream IL-13 signaling. Therapeutic success with tralokinumab in atopic dermatitis (but not asthma) supports the hypothesis that blockade of the cytokine IL-13 alone is sufficient to improve symptoms of atopic dermatitis.

Tralokinumab is eliminated by non-saturable proteolysis.

The half-life is 22 days. This is consistent with the typical estimate for human IgG4 monoclonal antibodies directed against soluble cytokines. In ECZTRA 1, ECZTRA 2, and ECZTRA 3, a clearance of 0.149 l/day was determined by population PK analysis.

In Phase I studies with intravenous administration, clearance was determined to be between 0.179 and 0.211 l/day.

Asthma: Tralokinumab was primarily developed for the treatment of severe, uncontrolled asthma. Here, the efficacy and safety of tralokinumab could not be adequately demonstrated. Further testing in this condition was therefore discontinued (Panettieri RA Jr et al 2018).

Atopic dermatitis: In contrast, tralokinumab rapidly and persistently relieved symptoms of atopic dermatitis in a phase II study (Wollenberg A et al. 2019). Tralokinumab was shown to have good effects both as monotherapy and in combination with topical corticosteroids in adults with moderate-to-severe atopic dermatitis.

In June 2018, a phase IIb study was published that illustrated that the monoclonal antibody tralokinumab successfully relieved symptoms in patients with moderate-to-severe AD. This study also evaluated the effect of tralokinumab on health-related quality of life compared to placebo in 52 adult patients. Patients treated with the antibody showed statistically significant and clinically relevant improvements compared with placebo in nearly all aspects of health-related quality of life from week 12 (Silverberg J et al. 2018).

Tralokinumab has been approved for the treatment of moderate-to-severe atopic dermatitis in adults since June 2021.

Tralokinumab (Adtralza®⁾ has been approved since 2022 for patients 12 years of age and older with moderate-to-severe atopic dermatitis (AD).

Hypersensitivity: If a systemic hypersensitivity reaction (immediate or delayed) occurs, the use of tralokinumab should be discontinued and appropriate therapy initiated.

Conjunctivitis: Patients treated with tralokinumab who develop conjunctivitis that does not resolve after standard treatment should undergo ophthalmologic evaluation.According to the assessment from current European guidelines on atopic dermatitis, fewer acute complications are expected ungtner tralokinumab than, for example, drug therapy with dupilumab.

Helminthosis: Patients with known helminthosis were excluded from participation in clinical trials. It is not known whether tralokinumab affects the immune response to helminthosis by inhibiting the IL-13 pathway. Patients with existing helminthosis should be treated before initiating tralokinumab therapy. If patients become infected during tralokinumab therapy and do not respond to treatment for helminthosis, treatment with tralokinumab should be interrupted until the infection has resolved.

Pregnancy: To date, there is limited experience with the use of tralokinumab in pregnant women. Animal studies revealed no evidence of direct or indirect adverse health effects related to reproductive toxicity. As a precaution, use of tralokinumab during pregnancy should be avoided.

Lactation: It is not known whether tralokinumab passes into breast milk or is absorbed systemically after ingestion. A decision must be made as to whether to discontinue breastfeeding or to refrain from treatment with tralokinumab. Both the benefit of breastfeeding for the child and the benefit of the therapy for the woman should be considered.

Tralokinumab is injected subcutaneously into the thigh or abdomen, outside a 5 cm area around the belly button. If administered by another person, the injection may also be given in the upper arm.

The recommended dose for adults is 600 mg of tralokinumab (four injections of 150 mg each) as a starting dose, followed by 300 mg (two injections of 150 mg each) every two weeks as a subcutaneous injection.

The most common adverse reactions with the use of tralokinumab are:

• Upper respiratory tract infections; mainly reported as colds (23.4%)
• Injection site reactions (7.2%)
• conjunctivitis (5.4%)
• allergic conjunctivitis (2.0%)

The following interactions should be considered when using tralokinumab:

• Inactivated vaccines: Immune responses to inactivated vaccines were evaluated in a study in adults with atopic dermatitis. As there were no differences in antibody responses, patients treated with tralokinumab may receive inactivated vaccines or inactivated vaccines concurrently.
• Live vaccines and live attenuated vaccines: Live vaccines and live attenuated vaccines should not be used concomitantly with tralokinumab because clinical safety and efficacy have not been established. Therefore, it is recommended to update patients' vaccination status with live vaccines and live attenuated vaccines according to current vaccination recommendations prior to treatment with tralokinumab.

Tralokinumab must not be used in case of hypersensitivity to the active substance or to any of the other ingredients of the medicinal product mentioned.

Vaccines: Live and live attenuated vaccines must not be used concomitantly with tralokinumab because clinical safety and efficacy have not been established. Immune responses to tetanus booster vaccine and meningococcal vaccine have been studied. It is recommended that patients' vaccination status be updated with live and live attenuated vaccines according to current vaccination recommendations prior to treatment with tralokinumab.

Tralokinumab is available on the market as ^Adtralza®. It shows a safety profile at placebo level. In the initial phase up to 16 weeks, the safety profile of ^Adtralza® was at placebo level. In the long-term use, no new signals appeared. The conjunctivitis rate remained permanently low. Long-term safety is particularly relevant in view of the long-term therapy usually required. ^Adtralza® offers patients long-term disease control, a good long-term safety profile and thus significantly better quality of life.

Trafficability: Tralokinumab has no or negligible effect on trafficability and ability to operate machinery.

1. Blair HA (2022) Tralokinumab in Atopic Dermatitis: A Profile of Its Use. Clin Drug Investig 42: 365-374.

2. Specialized information Adtralza, LEO Pharma, sgtand October 2022.

3. Panettieri RA Jr et al (2018) Tralokinumab for the treatment of severe, uncontrolled asthma: the ATMOSPHERE clinical development program. Immunotherapy 10: 473-490.

4. Panettieri RA Jr et al (2018) Tralokinumab for severe, uncontrolled asthma (STRATOS 1 and STRATOS 2): two randomised, double-blind, placebo-controlled, phase 3 clinical trials. Lancet Respir Med 6:511-525.
5. Parker JM et al (2018) A phase 2 randomized controlled trial of tralokinumab in subjects with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 197:94-103.
6. Russell RJ et al (2018) MESOS study investigators. Effect of tralokinumab, an interleukin-13 neutralising monoclonal antibody, on eosinophilic airway inflammation in uncontrolled moderate-to-severe asthma (MESOS): a multicentre, double-blind, randomised, placebo-controlled phase 2 trial. Lancet Respir Med 6: 499-510.
7. Silverberg J et al: Treatment with tralokinumab improves healthrelated quality of life in adult patients with moderate to severe atopic dermatitis: results from a phase 2b, randomized, double-blind, placebo-controlled study. EADV 2018; Abstract P0281.
8. Wollenberg A et al (2019) Treatment of atopic dermatitis with tralokinumab, an anti-IL-13 mAb. J Allergy Clin Immunol 143:135-141.
9. Wollenberg A et al.(2022) European guideline (EuroGuiDerm) on atopic eczema: part I - systemic therapy. J Eur Acad Dermatol Venereol 36:1409-1431.