Long-Term Safety and Efficacy of Tralokinumab in Adults and Adolescents with Moderate-to-Severe Atopic Dermatitis Treated for up to 6 Years

Abstract

Introduction: Tralokinumab, a monoclonal antibody that specifically neutralizes interleukin-13, is indicated for the treatment of moderate-to-severe atopic dermatitis (AD) in patients ≥12 years of age. ECZTEND (NCT03587805) is an open-label extension study evaluating the long-term safety and efficacy of tralokinumab in patients with moderate-to-severe AD. Interim analyses previously demonstrated the benefit-risk profile of tralokinumab in patients followed up to 3.5 years in ECZTEND; here, we present the final study results.

Methods: Patients completing any of 9 parent trials (ECZTRA 1-8 and the TraSki investigator-initiated study) were able to enter ECZTEND. Patients in ECZTEND received tralokinumab 300 mg every other week, with topical corticosteroids and/or calcineurin inhibitors allowed. The primary objective of ECZTEND was to assess safety of tralokinumab treatment from baseline up to Week 268. Secondary objectives were to assess efficacy, including proportions of patients achieving Investigator’s Global Assessment score of 0 or 1 (IGA 0/1; clear/almost clear skin) or ≥75% improvement in Eczema Area and Severity Index (EASI-75) from parent trial baseline, and quality of life (QoL) measures up to Week 248.

Results: In total, 1672 patients were treated with tralokinumab for up to 5.1 years in ECZTEND. Median exposure was 2.6 years, with 4466.2 total patient years of exposure. Maximum tralokinumab exposure, including the parent trial period, was 6.1 years. In ECZTEND, exposure-adjusted incidence rate (IR) of patients with ≥1 treatment-emergent adverse event (AE) was 114.3, which was lower than the initial 16-week treatment period of the parent trials (IR=424.8 for tralokinumab; IR=475.3 for placebo). Over 5 years of ECZTEND, serious AEs were reported in 9.0% of patients (IR=3.54). AEs that led to permanent discontinuation of treatment occurred in 4.5% of patients (IR=1.71). The most frequently reported AEs (≥5% of patients) were nasopharyngitis (22.2%), dermatitis atopic (21.4%), coronavirus infection (17.9%), upper respiratory tract infection (8.8%), headache (6.8%), and conjunctivitis (6.2%). Pre-defined AEs of special interest (eye disorders, skin infections requiring systemic treatment, eczema herpeticum, malignancies) were observed at rates similar to, or lower than, the initial treatment period of the parent trials. At Week 248, response rates (95% CI) for IGA 0/1 and EASI-75 were 66.7% (56.1-75.8) and 92.9% (85.3-96.7), respectively. Additionally, itch, sleep, and QoL improvements were sustained at levels equivalent to no-to-mild disease throughout ECZTEND.

Conclusions: Long-term use of tralokinumab, up to 1 year in parent trials plus up to 5 years in ECZTEND, was well-tolerated with no new safety signals identified in patients aged 12 and up with moderate-to-severe AD. Tralokinumab treatment demonstrated robust long-term efficacy with sustained improvements in AD signs, symptoms, and QoL.