IL-13 plays a key role in 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 to assess 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.
- 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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