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)

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 center dot 2% vs. 50 center dot 5%; difference 14 center dot 1% (95% confidence interval 2 center dot 5-25 center dot 7); P = 0 center dot 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.