Tralokinumab plus topical corticosteroids for the treatment of moderate-to-severe atopic dermatitis: results from the double-blind, randomized, multicentre, placebo-controlled phase III ECZTRA 3 trial

Abstract

Background: Tralokinumab is a fully human monoclonal antibody that specifically neutralizes interleukin-13, a key driver of atopic dermatitis (AD).

Objectives: To evaluate the efficacy and safety of tralokinumab in combination with topical corticosteroids (TCS) in patients with moderate-to-severe AD who were candidates for systemic therapy.

Methods: This was a double-blind, placebo plus 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 every 4 weeks (Q4W), with TCS as needed, for another 16 weeks.

Results: At week 16, more patients treated with tralokinumab than with placebo achieved IGA 0/1: 38·9% vs. 26·2% [difference (95% confidence interval): 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% of those 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 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 was similar across treatment groups.

Conclusions: Tralokinumab 300 mg in combination with TCS as needed was effective and well tolerated in patients with moderate-to-severe AD.

Figure 1

Trial design. Clinical response is defined as patients achieving Investigator’s Global Assessment score of 0/1 or at least 75% reduction in the Eczema Area and Severity Index. AD, atopic dermatitis; Q2W, every 2 weeks; Q4W, every 4 weeks; TCS, topical corticosteroids.

Figure 2

(a) IGA score of 0/1 and (b) EASI 75 response by visit in the initial treatment period, full analysis set. Patients who received rescue medication were considered nonresponders. Patients with missing data were imputed as nonresponders. The number of patients assessed at each visit can be found in Tables S2 and S3; see Supporting Information. *P < 0·05 vs. placebo + TCS; **P < 0·01 vs. placebo + TCS; ***P < 0·001 vs. placebo + TCS. Model‐based treatment difference: ^† P < 0·05 vs. placebo + TCS; ^‡ P < 0·001 vs. placebo + TCS. EASI 75, at least 75% reduction in Eczema Area and Severity Index; IGA, Investigator’s Global Assessment; Q2W, every 2 weeks; TCS, topical corticosteroids.

Figure 3

Effect of tralokinumab and placebo treatment on secondary endpoint: (a) change from baseline in SCORAD score by visit; (b) change from baseline in weekly average of worst daily pruritus NRS score; and (c) change from baseline in DLQI score by visit, repeated‐measurements analysis, initial treatment period, full analysis set. Data are adjusted mean change (SE) from repeated‐measurements model. Data collected after permanent discontinuation of investigational medicinal product or initiation of rescue medication not included. The number of patients assessed at each visit can be found in Tables S6–S9; see Supporting Information. In case of no postbaseline assessments before indication of rescue medication, the week 2 (week 1 for NRS) change will be imputed as 0. Repeated‐measurements model: Change = Treatment × Week + Baseline × Week + Region + Baseline Investigator’s Global Assessment. *P < 0·05 vs. placebo + TCS; **P < 0·01 vs. placebo + TCS; ***P < 0·001 vs. placebo + TCS. DLQI, Dermatology Life Quality Index; NRS, Numeric Rating Scale; Q2W, every 2 weeks; SCORAD, SCORing Atopic Dermatitis; SE, standard error; TCS, topical corticosteroids.

Figure 4

Cumulative amount of TCS use by visit and treatment group, assuming no TCS used from the nonreturned tubes, initial treatment period, full analysis set. Data are adjusted mean (SE) from repeated‐measurements model. Data collected after permanent discontinuation of investigational medicinal product or initiation of rescue medication not included. Repeated‐measurements model: TCS cumulative amount (g) = Treatment × Week + Region + Baseline Investigator’s Global Assessment. *P < 0·05 vs. placebo + TCS; **P < 0·01 vs. placebo + TCS. Q2W, every 2 weeks; SE, standard error; TCS, topical corticosteroids.

Figure 5

IGA score of 0/1 and EASI 75 response at week 32, patients in the continuation treatment analysis set with IGA score of 0/1 (left) and EASI 75 (right) at week 16 achieved without rescue medication after initial randomization to tralokinumab. A responder was defined as having an IGA score of 0/1 or EASI 75. N = number of individuals being IGA 0/1 (left) and EASI 75 (right) responders at week 16 and initially treated with tralokinumab. n = number of responders at week 32. Patients who received rescue medication were considered nonresponders. Patients with missing data at week 32 were imputed as nonresponders. EASI 75, at least 75% reduction in Eczema Area and Severity Index; IGA, Investigator’s Global Assessment; Q2W, every 2 weeks; Q4W, every 4 weeks; TCS, topical corticosteroids.