551 - Continuous tralokinumab treatment over 4 years in adults with moderate-to-severe atopic dermatitis provides long-term disease control
Authors: Blauvelt Andrew , Langley Richard G , Peris Ketty , Silvestre Juan Francisco , Katoh Norito , Tauber Marie , Pinter Andreas , Ameen Mahreen , Gooderham Melinda , Øland Christian Bjerregård , Tindberg Ann-Marie , Gjerum Le , Reich Kristian 
Published: February 2024

Abstract

Introduction/Background
There is a need for additional long-term treatment options for patients with moderate-to-severe atopic dermatitis (AD) that provide sustained disease control with a favorable safety profile. Tralokinumab, a monoclonal antibody that specifically neutralizes interleukin-13, is approved for the treatment of moderate-to-severe AD in multiple countries. Clinical trials of up to 52-wk duration showed that tralokinumab was effective and well tolerated as monotherapy and in combination with topical therapy. ECZTEND (NCT03587805) is an ongoing open-label, 5-yr extension trial investigating the long-term safety and efficacy of tralokinumab ± optional topical corticosteroids (TCS).

Objectives
To assess the efficacy of long-term tralokinumab treatment, we conducted a post hoc interim subgroup analysis restricted to the largest, most homogenous patient population, with the longest treatment duration.

Methods
Adult patients with moderate-to-severe AD who were continuously treated with tralokinumab ± optional TCS for 52 wks in the parent phase 3 trials ECZTRA 1 (NCT03131648) or ECZTRA 2 (NCT03160885) and for up to 152 wks in ECZTEND as of data cutoff April 30, 2022, were included. Endpoints included proportion of patients achieving Investigator’s Global Assessment (IGA) score of 0/1 (clear/almost clear skin), at least 75% or 90% improvement in Eczema Area and Severity Index (EASI) relative to parent trial baseline (EASI-75 or EASI-90), EASI ≤7, worst weekly pruritus Numeric Rating Scale (NRS) ≤4, and Dermatology Life Quality Index (DLQI) ≤5. Results are presented using observed data. Sensitivity analyses on patients who completed Wk 152 in ECZTEND (or who withdrew, but were enrolled in the study at least 152 wks prior to the study cutoff) were performed using modified non-responder imputation (mNRI) with discontinuations due to AEs or lack of efficacy imputed as non-responders and a 2-step multiple imputation (MI) for other missing data [Step 1: Missing data up to 1 year in ECZTEND were imputed using a standard regression-based MI method; Step 2: Missing data post 1 year imputed by carrying forward the within-subject area under the curve of days in-response].

Results
347 adult patients with a mean age (SD) of 42.2 (14.5) yrs and a mean EASI (SD) of 30.8 (13.7) at parent trial baseline were included in this analysis. After 4 yrs of total tralokinumab treatment (at Wk 152 in ECZTEND), IGA 0/1 [% (n/N)] was observed in 52.6% (92/175) of patients. EASI-75 {% (n/N) [95% CI]} was achieved in 84.5% (147/174) [78.4, 89.1] of patients as observed, and in 73.4% (254.8/347) [68.6, 78.3] using mNRI. EASI-90 was achieved in 64.4% (112/174) [57.0, 71.1] of patients as observed, and in 53.4% (185.2/347) [47.8, 59.0] using mNRI. Additionally, EASI ≤7 (mild disease) was observed in 84.5% (147/174) of patients, worst weekly pruritus NRS ≤4 (no to mild itch) in 68.0% (119/175), and DLQI ≤5 (no to small effect of AD on quality of life) in 79.0% (128/162) of patients. The safety profile was favorable and consistent with earlier analyses, with no new safety signals arising with continued tralokinumab use.

Conclusions
Continuous use of tralokinumab ± optional TCS provided long-term disease control over 4 yrs in adult patients with moderate-to-severe AD.