555 - Safety of tralokinumab for the treatment of atopic dermatitis in patients with up to 4.5 years of treatment: an updated integrated analysis of eight clinical trials
Authors: Reich Kristian , Langley Richard G , Silvestre Juan Francisco , Staumont-Salle Delphine , Costanzo Antonio , Pink Andrew , Paller Amy , Katoh Norito , Wollenberg Andreas , Warren Richard B , Øland Christian Bjerregård , Tindberg Ann-Marie , Gjerum Le , Simpson Eric 
Published: February 2024

Abstract

Introduction/Background
Tralokinumab, a monoclonal antibody that specifically neutralizes interleukin-13, is indicated for the treatment of patients (pts) with moderate-to-severe AD. Clinical trials of up to 52 weeks’ duration, showed that tralokinumab was efficacious and well tolerated as monotherapy and in combination with topical therapy.

Objectives
To evaluate the long-term safety of tralokinumab in an integrated analysis of seven phase 3 parent trials of up to 52 weeks’ duration (NCT03131648, NCT03160885, NCT03363854, NCT03562377, NCT03526861, NCT03761537, NCT04587453), and the ongoing, up to 5-year extension study (ECZTEND; NCT03587805).

Methods
Two datasets were analyzed: a placebo-controlled (PC) dataset from the initial 16-wk period of the parent trials and an all-tralokinumab (AT) dataset combining the parent trials with the subsequent ECZTEND trial including pts from first dose of tralokinumab until end of tralokinumab exposure or data cut-off (April 30th, 2022). Exposure was defined over the active treatment periods. For the AT dataset, periods on placebo were disregarded. All treatment-emergent adverse events (AEs) were recorded. AEs of special interest (AESIs) were predefined. Proportions of pts with events and incidence rates (IR) per 100 patient-years of exposure (PYE) were calculated. PYE was defined as the time until the first event or exposure end, whichever came first, and incidence was defined as the first event.

Results
In total, 2693 pts (≥12 years) received tralokinumab for up to 238.5 weeks (≈4.5 years) with a median exposure time of 76.5 weeks in the AT dataset. Total exposure time was 5320.2 patient years. Median age at baseline was 33.0 years (min-max; 12-92). 10.4% of pts were 12-17 years. Overall, 2307 pts experienced an AE (IR=202.0), most (97.3%) of which were mild-to-moderate. Serious AEs (SAEs) were reported in 226 pts (IR=4.5); SAEs were considered possibly or probably related by the investigator in 50 pts (IR=0.9). No SAEs at the preferred term level were reported with an IR≥0.1. Discontinuation of treatment due to AEs was low (IR=2.8). AEs leading to drug withdrawal with an IR&gt;0.1 were dermatitis atopic (IR=0.5) and injection site reaction (ISR) (IR=0.2). The most frequently reported AEs in the AT dataset were consistent with the PC dataset, including nasopharyngitis (IR=18.4), upper respiratory tract infection (IR=6.9), conjunctivitis (IR=5.0), ISR (IR=3.6), conjunctivitis allergic (IR=2.7), and injection site pain (IR=1.5). AESIs, including eye disorders, skin infections requiring systemic treatment, eczema herpeticum, and malignancies, were observed in the AT dataset at rates similar to or lower than reported in the PC dataset.

Conclusions
Long-term use of tralokinumab, for up to 4.5 years, was well tolerated, and the pattern of AEs was consistent with the initial placebo-controlled treatment period and with no new safety signals identified.