Amlitelimab therapy leads to sustained decrease of IL-22 in AD patients

Amlitelimab treatment significantly decreased serum levels of interleukin (IL)-22, which essentially affects the immune dysregulation in atopic dermatitis (AD), well after the last application. Hence, this may explain its efficacy in a previously presented randomised, placebo-controlled, phase 2a trial in patients with moderate-to-severe AD.  

Amlitelimab is a fully human, non-depleting, non-cytotoxic, anti-OX40 ligand, monoclonal antibody, that inhibits the engagement of OX40 ligand in antigen-presenting cells and blocks both T helper 2 and T helper 1/17/22 cells, which are central to the inflammation and pathological outcomes in AD. Dr Stephan Weidinger (University Hospital Schleswig-Holstein, Germany) and his team evaluated the effects of amlitelimab on IL-22, an important T helper 22 cell-associated disease mediator of AD [1]. Presented was an exploratory serum analysis from patients with moderate-to-severe AD,  participating to  a double-blind, placebo-controlled, multicentre, phase 2a trial, whose results were presented at a previous meeting [2].

The trial recruited 78 patients, randomised 1:1:1 to intravenous amlitelimab low dose (200 mg/100 mg maintenance every 4 weeks; n=27), high dose (500 mg/250 mg; n=27), or placebo until week 12. Percentage change in Eczema Area and Severity Index (EASI) from baseline to week 16 was the primary efficacy endpoint. In this trial, amlitelimab was well tolerated, with an unremarkable safety profile. The mean percentage change in EASI at week 16 from baseline was -80.12% for low dose amlitelimab (P=0.009) and -69.97% for high dose amlitelimab (P=0.072) versus -49.37% for placebo. Moreover, responders had sustained clinical responses up to week 36.

Serum was collected at baseline, week 4, and week 16, and in the case of responders also at week 24 and week 36. Ultra-sensitive single-molecule immune assay (Simoa) ascertained the IL-22 level.

No difference was detected in the levels of IL-22 between the groups at baseline. Yet, the IL-22 level correlated with disease severity at baseline as measured by EASI (r=0.53; P<0.0001) and Scoring of atopic dermatitis (SCORAD) (r=0.36; P=0.001). Furthermore, a significant reduction in IL-22 levels was observed at week 16 in participants treated with amlitelimab (low-dose P<0.0001; high-dose P=0.001) but not in the placebo group (P=0.381). The amlitelimab-induced decrease in IL-22 levels remained consistent until week 36 in responders, so the strong reduction of IL-22 extended beyond the last application of amlitelimab.

“To conclude, in this phase 2a study, amlitelimab treatment not only induced significant improvements in patients with AD but also significantly reduced serum levels of IL-22, which is an important disease mediator. In good responders, this reduction of IL-22 was maintained up to week 36, so 24 weeks after the last application,” Prof. Weidinger concluded. A phase 2b study is now enrolling participants.

1. Weidinger S, et al. Treatment with amlitelimab - a novel non-depleting, non-cytotoxic anti-OX40Ligand monoclonal antibody - reduces IL-22 serum levels in a Phase 2a randomised, placebo-controlled trial in patients with moderate-to-severe atopic dermatitis. Abstract No 743, EADV Congress 2022, Milan, Italy, 7–10 September.
2. Weidinger S, et al. Abstract 203, RAD 2022 Virtual, 9‒11 April.

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Posted on 5 November 20225 November 2022