Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2)

Abstract

Background: Tralokinumab, a fully human monoclonal antibody, specifically neutralizes interleukin-13, a key cytokine driving peripheral inflammation in atopic dermatitis (AD). In phase II studies, tralokinumab combined with topical corticosteroids provided early and sustained improvements in AD signs and symptoms.

Objectives: To evaluate the efficacy and safety of tralokinumab monotherapy in adults with moderate-to-severe AD who had an inadequate response to topical treatments.

Methods: In two 52-week, randomized, double-blind, placebo-controlled, phase III trials, ECZTRA 1 and ECZTRA 2, adults with moderate-to-severe AD were randomized (3 : 1) to subcutaneous tralokinumab 300 mg every 2 weeks (Q2W) or placebo. Primary endpoints were Investigator's Global Assessment (IGA) score of 0 or 1 at week 16 and ≥ 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16. Patients achieving an IGA score of 0 or 1 and/or EASI 75 with tralokinumab at week 16 were rerandomized to tralokinumab Q2W or every 4 weeks or placebo, for 36 weeks. The trials were registered with ClinicalTrials.gov: NCT03131648 and NCT03160885.

Results: At week 16, more patients who received tralokinumab vs. placebo achieved an IGA score of 0 or 1: 15·8% vs. 7·1% in ECZTRA 1 [difference 8·6%, 95% confidence interval (CI) 4·1-13·1; P = 0·002] and 22·2% vs. 10·9% in ECZTRA 2 (11·1%, 95% CI 5·8-16·4; P < 0·001) and EASI 75: 25·0% vs. 12·7% (12·1%, 95% CI 6·5-17·7; P < 0·001) and 33·2% vs. 11·4% (21·6%, 95% CI 15·8-27·3; P < 0·001). Early improvements in pruritus, sleep interference, Dermatology Life Quality Index, SCORing Atopic Dermatitis and Patient-Oriented Eczema Measure were observed from the first postbaseline measurements. The majority of week 16 tralokinumab responders maintained response at week 52 with continued tralokinumab treatment without any rescue medication (including topical corticosteroids). Adverse events were reported in 76·4% and 61·5% of patients receiving tralokinumab in ECZTRA 1 and ECZTRA 2, respectively, and in 77·0% and 66·0% of patients receiving placebo in ECZTRA 1 and ECZTRA 2, respectively, in the 16-week initial period.

Conclusions: Tralokinumab monotherapy was superior to placebo at 16 weeks of treatment and was well tolerated up to 52 weeks of treatment.

Figure 1

Achievement of (a) Investigator’s Global Assessment (IGA) score of 0 or 1 and (b) ≥ 75% improvement in Eczema Area and Severity Index (EASI 75) in the 16‐week initial treatment period in ECZTRA 1 and ECZTRA 2. Patients who received rescue medication were considered nonresponders. Patients with missing data at week 16 were imputed as nonresponders. The Cochran–Mantel–Haenszel test was used, stratified by region and baseline IGA. ^* P < 0·05 vs. placebo, ^** P < 0·01 vs. placebo, ^*** P < 0·001 vs. placebo. ^† P = 0.002 vs. placebo. Q2W, every 2 weeks.

Figure 2

Maintenance of (a) Investigator’s Global Assessment (IGA) score of 0 or 1 and (b) ≥ 75% improvement in Eczema Area and Severity Index (EASI 75) clinical response at week 52 in ECZTRA 1 and ECZTRA 2. Patients who, after week 16, received rescue medication or were transferred to open‐label treatment were considered nonresponders at week 52. Missing values were imputed as nonresponse. The Cochran–Mantel–Haenszel test was used, stratified by region. Maintenance of IGA 0 or 1 was assessed in patients achieving the week 16 primary outcome of IGA score of 0 or 1 without use of rescue medication after initial randomization to tralokinumab. EASI 75 was assessed in patients achieving the week 16 primary outcome of EASI 75 without use of rescue medication after initial randomization to tralokinumab. ^** P < 0·01, vs. placebo ^*** P < 0·001 vs. placebo. Q2W, every 2 weeks; Q4W, every 4 weeks.

Figure 3

Example of improvement in Eczema Area and Severity Index (EASI) from baseline to week 16 in a patient receiving tralokinumab. IGA, Investigator’s Global Assessment; NRS, numerical rating scale.