Tralokinumab is a fully human monoclonal antibody that specifically neutralizes interleukin-13, a key driver of atopic dermatitis (AD).To evaluate the efficacy and safety of tralokinumab in combination with TCS in patients with moderate-to-severe AD who were candidates for systemic therapy.This was a double-blind, placebo plus optional TCS-controlled phase III trial. Patients were randomized 2 : 1 to subcutaneous tralokinumab 300 mg or placebo every 2 weeks (Q2W) with TCS as needed over 16 weeks. Patients who achieved an Investigator's Global Assessment (IGA) score of 0/1 and/or 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16 with tralokinumab were rerandomized 1 : 1 to tralokinumab Q2W or Q4W, with TCS as needed, for another 16 weeks.At week 16, more tralokinumab-treated patients than placebo achieved IGA 0/1: 38·9% vs. 26·2% [difference (95% CI): 12·4% (2·9-21·9); P = 0·015] and EASI 75: 56·0% vs. 35·7% [20·2% (9·8-30·6); P < 0·001]. Of the patients who were tralokinumab responders at week 16, 89·6% and 92·5% treated with tralokinumab Q2W and 77·6% and 90·8% treated with tralokinumab Q4W maintained an IGA 0/1 and EASI 75 response at week 32, respectively. Among patients who did not achieve an IGA 0/1 and EASI 75 with tralokinumab Q2W at 16 weeks, 30·5%, and 55·8% achieved these endpoints, respectively, at week 32. The overall incidence of adverse events (AEs) was similar across treatment groups.Tralokinumab 300 mg in combination with TCS as needed was effective and well tolerated in patients with moderate-to-severe AD.