Tralokinumab Plus Topical Corticosteroids in Adults With Severe Atopic Dermatitis and Inadequate Response to or Intolerance of Ciclosporin A

A Placebo-controlled, Randomized, Phase III Clinical Trial (ECZTRA 7)

J. Gutermuth; A.E. Pink; M. Worm; L. Soldbro; C. Bjerregård Øland; S. Weidinger


The British Journal of Dermatology. 2022;186(3):440-452. 

In This Article

Abstract and Introduction


Background: Patients with severe atopic dermatitis (AD) not controlled with topical therapy have limited treatment options. Ciclosporin A (CSA) is a commonly used, broad immunosuppressant in AD, but treatment with CSA requires monitoring for potentially serious adverse effects. In a previous phase III trial, tralokinumab plus topical corticosteroids (TCS) as needed provided early and sustained improvements in AD signs and symptoms.

Objectives: To evaluate the efficacy and safety of tralokinumab plus TCS in adult patients with severe AD whose disease was not adequately controlled with CSA or who had contraindications to oral CSA.

Methods: In this 26-week, multicentre, parallel, randomized, double-blind, placebo-controlled, phase III trial, European adults with severe AD were randomized 1 : 1 to subcutaneous tralokinumab 300 mg or placebo every 2 weeks plus TCS as needed. The primary endpoint was a 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16.

Results: In total, 277 patients were randomized. At week 16, more patients treated with tralokinumab plus TCS vs. placebo plus TCS achieved EASI 75 [64·2% vs. 50·5%; difference 14·1% (95% confidence interval 2·5–25·7); P = 0·018], which increased further up to week 26. Improvements in AD severity were accompanied by early improvements in patient-reported outcomes, including Dermatology Life Quality Index, Patient-Oriented Eczema Measure, pruritus and sleep interference. Tralokinumab plus TCS also showed a higher EASI75 response at week 16 among patients who had previously failed CSA therapy vs. placebo plus TCS (57% vs. 41%). The overall incidence of adverse events was similar between treatment arms.

Conclusions: Tralokinumab 300 mg plus TCS as needed was effective and well tolerated in patients with severe AD whose disease was not adequately controlled with CSA or who had contraindications to oral CSA.


Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by intense pruritus and recurrent dry, red and excoriated patches.[1] AD is associated with sleep disturbance, anxiety, depression and work absenteeism,[2–4] which places a substantial burden on patients and society.[5,6]

Management of AD is aimed at long-term control of the disease, preventing flares and avoiding adverse events (AEs).[4] According to guidelines and consensus statements, patients with AD who fail or are intolerant of topical treatments should be treated systemically with immunosuppressants or biologics.[4,7–9] Therapies currently used for the systemic treatment of moderate-to-severe AD include immunosuppressants, such as corticosteroids, ciclosporin A (CSA), methotrexate and azathioprine, which may be associated with toxicities, in addition to one biologic, dupilumab, and a small-molecule inhibitor of Janus kinase, baricitinib.[4,10] Topical corticosteroids (TCS) and topical calcineurin inhibitors are commonly used in combination with these therapies; however, their efficacy is affected by patient adherence. Achieving the right balance of efficacy and safety is a critical factor in patients' preferences in relation to treatment.[11,12] The range of systemic treatment options that provide sustained disease control and have an acceptable safety profile is still limited.[7,8,13–15]

CSA is considered a first-line treatment for patients with severe AD in some countries; however, it is approved for use only in Europe and Japan and has limitations to its use.[4,8] CSA use is associated with side-effects and requires close monitoring for signs of hypertension and nephrotoxicity; therefore, continuous treatment beyond 2 years is not recommended and some suggest a treatment duration of only 3–6 months.[4,8] With limited treatment options, patients with severe AD who have inadequate response with CSA or are ineligible for CSA are an important patient population to investigate.

Tralokinumab is a fully human immunoglobulin G4 monoclonal antibody that specifically targets the interleukin-13 cytokine, a key driver of the signs and symptoms of AD.[16,17] Tralokinumab, used concomitantly with TCS or as monotherapy, was effective and well tolerated with a favourable benefit–risk profile in phase II and III trials in patients with moderate-to-severe AD.[18–20]

The aim of this trial was to evaluate the efficacy and safety of tralokinumab plus TCS as needed in a European population of adult patients with severe AD whose disease was not adequately controlled with CSA or who had contraindications to oral CSA.