IL-22 receptor blocker reduces itch and skin lesions in AD

IL-22 might be a novel therapeutic target in the therapy of moderate-to-severe atopic dermatitis (AD) as it has a profound effect on multiple inflammatory pathways in AD. In a first phase 2a study in patients with moderate-to-severe AD, the investigative IL-22 receptor blocker LEO138559 showed high efficacy and was well tolerated.

Blockade of IL-22 has shown to be associated with a significant downregulation of multiple immune pathways, such as Th1/CXCL9 [1]. The expression of this proinflammatory cytokine is increased and thought to contribute to epidermal hyperplasia and barrier defects in patients with AD. Prof. Diamant Thaçi (University of Lübeck, Germany) presented the results of a phase 2a, randomised, double-blind, placebo-controlled, proof-of-concept trial (NCT04922021) to assess the efficacy and safety of LEO138559, a monoclonal antibody that specifically targets the IL-22 receptor, blocking signalling of IL-22 and potentially also IL-20 and IL-24 [2]. Included were 58 patients, randomised 1:1 to receive the agent or placebo every 2 weeks for 16 weeks, followed by a 16-week safety follow-up.

At week 16, the Eczema Area and Severity Index (EASI) change from baseline, the primary study endpoint, was -15.3 in the participants treated with LEO138559, a 65.4% improvement compared with -3.5 in the placebo group (P=0.003). “The agent really works fast,” Prof. Thaçi said. In addition, the antibody was superior regarding all secondary endpoints, namely EASI75, EASI90, and EASI100 responses and in the Investigator’s Global Assessment scale. LEO138559 also had a pronounced antipruritic effect: 20% of the participants that got the active ingredient achieved a reduction in a numerical rating scale of ≥4 compared with 7 in the placebo group (P=0.14).

The new antibody showed good tolerability with no serious adverse events and only 1 case of conjunctivitis.

1. Brunner PM, et al. J Allergy Clin Immunol 2019;143:142–54.
2. Thaçi, D. Efficacy and safety of IL-22R inhibition in patients with moderate-to-severe atopic dermatitis: results from a Phase 2a monotherapy trial. S042, AAD 2023 Annual Meeting, 17–21 March, New Orleans, USA.

Posted on 15 May, 2023