IL-13 plays a key role in the pathogenesis of atopic dermatitis (AD). The phase 3 ECZTRA trials demonstrated the remarkable efficacy of the IL-13 blocker tralokinumab in adult patients with moderate-to-severe AD .
AD is a chronic inflammatory skin disease. Tralokinumab is a fully human monoclonal antibody designed specifically to neutralise IL-13, a key driver of the underlying inflammation in AD, as Prof. Eric Simpson (Oregon Health & Science University, USA) explained. Recent data has suggested that IL-13 is the key type-2 cytokine driving inflammation in the periphery: IL-13 is overexpressed locally and has a significant impact on skin biology, including the recruitment of inflammatory cells, the alteration of the skin microbiome, and the decrease in the epidermal barrier function .
In the randomised, placebo-controlled, multinational phase 3 ECZTRA 1 and ECZTRA 2 trials, patients with moderate-to-severe AD (n=800 in ECZTRA 1; n=794 in ECZTRA 2) were randomised 3:1 to subcutaneous tralokinumab monotherapy (300 mg) or placebo every 2 weeks for 16 weeks. Primary endpoints were the percentage of participants with almost clear or clear skin according to the Investigator’s Global Assessment (IGA) score (0/1), and the percentage of patients with an improvement of the Eczema Area and Severity Index (EASI) score by 75%, achieved without the use of rescue medication. Most of the participants suffered from severe AD (IGA 4). At baseline, mean EASI scores were 32.4 (ECZTRA 1) and 32.2 (ECTZRA 2).
At week 16, patients who achieved these endpoints (i.e. responders) were re-randomised 2:2:1 to tralokinumab every 2 or every 4 weeks or placebo for a further 36-week maintenance phase. Placebo responders continued with placebo and all non-responders received open-label tralokinumab every 2 weeks with optional topical corticosteroids. Prof. Simpson explained that this design allows assessment of what happens if patients that are clear or almost clear at week 16 change the frequency of dosing.
At week 16, 15.8% of patients in the tralokinumab group compared with 7.1% in the placebo group gained an IGA 0/1 response (P=0.002) in the ECZTRA 1 trial. Corresponding numbers in the ECTZRA 2 trials were 22.2% versus 10.9% (P<0.001). A significant effect of tralokinumab was also seen with regard to the EASI 75 response: in the ECZTRA 1 trial, 25.0% in the tralokinumab group versus 12.7% in the placebo group, and in the ECZTRA 2 trial 33.2% versus 11.4%, respectively (P<0.001 for both comparisons).
At week 52, 59.6% and 55.8% of patients in both trials maintained EASI 75 with tralokinumab every 2 weeks; responses were similar in the group that received tralokinumab every 4 weeks. The overall adverse event rate was similar between tralokinumab every 2 weeks and placebo over 16 weeks; there were no new side effects seen until week 52.
For more articles on Type 2 Inflammation, see our independent webportal inflammation-type2.org.
- Simpson E, et al. Late-breaking abstract, AAD Virtual Meeting Experience, 12-14 June 2020.
- Bieber T. Allergy. 2020;75:54-62.
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Table of Contents: AAD 2020
Letter from the Editor
AAD 2020 Highlights Podcast
IL-17A and IL-17F blockade remarkably effective in psoriasis
Good response and pruritus reduction in AD with novel selective JAK1 inhibitor
Novel IL-23 blocker risankizumab highly effective and tolerable in psoriasis
IL-13 blocker tralokinumab effective in AD
Tape stripping – a painless way to distinguish AD and psoriasis?
IL-4/IL-13 blocker dupilumab effective in children with severe AD
Pembrolizumab leads to higher toxicity risk in obese melanoma patients
Can gene expression help to pick the right biologic to treat psoriasis in cancer patients?
Omalizumab for cancer-induced dermatoses
Psoriasis – What Is Hot?
Psoriasis therapy for children and pregnancies
Biologic psoriasis treatment to lower cardiovascular risk?
A new topical PDE-4 inhibitor effective in psoriasis
Systemic Therapies for Dermatologists
How to manage cutaneous side effects of immunotherapy
Cannabinoids: a future role in dermatology?
Hidradenitis Suppurativa/Acne Inversa
Biologics in HS – a growing armamentarium
Pearls of the Posters
Selective IL-23 blocker safe in elderly psoriasis patients
Spironolactone safe for androgenetic alopecia in cancer survivors
Baricitinib beneficial in head and neck AD
Continuous terbinafine most effective for toenail onychomycosis
ECLIPSE trial: skin clearance independent of PsA status at baseline
Biologics in HS – a growing armamentarium