Maurer, MarcusMarcusMaurerCheung, Dorothy S.Dorothy S.CheungTheess, WiebkeWiebkeTheessYang, XiaoyingXiaoyingYangDolton, Michael J.Michael J.DoltonGuttman, AnnaAnnaGuttmanChoy, David F.David F.ChoyDash, AjitAjitDashGrimbaldeston, Michele A.Michele A.GrimbaldestonSoong, WeilyWeilySoong2023-08-182023-08-182022https://publica.fraunhofer.de/handle/publica/44838310.1016/j.jaci.2022.08.0152-s2.0-8513902171936041655Background: The binding of IL-33 to its receptor ST2 (alias of IL1RL1) leads to the release of inflammatory mediators and may play a role in the pathogenesis of atopic dermatitis. Astegolimab is a fully human, IgG2 mAb that binds to ST2 and inhibits IL-33 signaling. Objectives: This study sought to assess the efficacy, safety, and pharmacokinetics of astegolimab in patients with atopic dermatitis. Methods: This was a randomized, placebo-controlled, phase 2 study in which adults with chronic atopic dermatitis were randomized 1:1 to receive astegolimab 490 mg every 4 weeks or placebo, for 16 weeks. The primary outcome was the percentage of change from baseline to week 16 of the Eczema Area and Severity Index score. Results: A total of 65 patients were enrolled in the study (placebo, n = 32; astegolimab, n = 33). The adjusted mean percentage of change from baseline to week 16 in the Eczema Area and Severity Index score was -51.47% for astegolimab compared with -58.24% for placebo, with a nonsignificant treatment difference of 6.77% (95% CI: -16.57-30.11; P = .5624). No differences were observed between treatment groups for secondary efficacy outcomes and in exploratory biomarkers (blood eosinophils, serum IL-5, serum CCL13). With the use of loading dose, pharmacokinetic exposure was sufficient from week 1. Astegolimab was well-tolerated, with a safety profile consistent with that observed in previous clinical trials. Conclusions: In patients with atopic dermatitis, astegolimab did not show a significant difference compared to placebo for the primary or secondary outcomes.enAtopic dermatitisIL-33ST2journal article