25854 Effects on type 2 immunity when specifically targeting the interleukin-13 cytokine with tralokinumab

Abstract

Interleukin (IL)-13 is a key driver of the skin inflammation seen in patients with atopic dermatitis (AD). Tralokinumab is a fully human monoclonal antibody that specifically binds to the IL-13 cytokine with high affinity, preventing interaction with the type 2 (IL-13 receptor[R]α1/IL-4Rα) receptor complex and subsequent IL-13 signaling. Tralokinumab demonstrated efficacy and safety in three Phase 3 trials. We investigated the effects of specific IL-13 targeting in randomly selected patients (n = 309) enrolled in the ECZTRA 1 trial, treated with either tralokinumab 300 mg every 2 weeks (q2w) [n = 233] or placebo (n = 76), who had blood samples taken that were analyzed for key serum biomarkers. Treatment with tralokinumab q2w resulted in a statistically significant percentage decrease in key T helper 2 (Th2) biomarkers of AD and atopy, such as chemokine ligand (CCL)17/thymus- and activation-regulated chemokine and periostin from baseline to week 4, and at week 16 (75% and 34% vs 41% and 16% for placebo, respectively) [both P ˂ .0001]. Tralokinumab treatment also reduced other Th2-related chemokines, including CCL13, CCL17, CCL22, and CCL26. The serum concentrations of total immunoglobulin E (IgE) also showed a significant reduction at week 16 vs baseline. The reduced levels of CCL17 and IgE support the hypothesis that neutralization of the IL-13 cytokine alone may suffice to prevent Th2 signaling, allowing for modulation of type 2 immunity, including a decrease in IgE, without the need for direct blocking of the IL-4 pathway.