IL-22 targeted monoclonal antibody(BioAtla)

Interleukin 22 promotes epidermal hyperplasia and inhibits skin barrier function.

Evaluate interleukin 22 blockade in adults with moderate-to-severe atopic dermatitis (AD).

We performed a randomized, double-blind, placebo-controlled trial with intravenous fezakinumab monotherapy every 2 weeks for 10 weeks, with follow-up assessments until 20 weeks. The change in SCOring AD (SCORAD) score from baseline at 12 weeks served as the primary end point.

At 12 weeks, the mean declines in SCORAD for the entire study population were 13.8 ± 2.7 in the fezakinumab arm and 8.0 ± 3.1 in the placebo arm (P = .134). In the severe AD patient subset (with a baseline SCORAD of ≥50), SCORAD decline was significantly stronger in the drug-treated patients than placebo-treated patients at 12 weeks (21.6 ± 3.8 vs 9.6 ± 4.2, P = .029) and 20 weeks (27.4 ± 3.9 vs 11.5 ± 5.1, P = .010). At 12 weeks, improvements in body surface area involvement in the entire population were significantly stronger in the drug-treated than placebo-treated patients (12.4% ± 2.4 vs 6.2% ± 2.7; P = .009), and in the severe AD subset, the decline in Investigator Global Assessment was significantly higher in the drug-treated than placebo-treated patients (0.7 ± 0.2 vs 0.3 ± 0.1; P = .034). All scores showed progressive improvements after last dosing (10 weeks) until end of study (20 weeks). Common adverse events were upper respiratory tract infections.

The limited sample size and lack of assessment with Eczema Area and Severity Index and a pruritus numerical rating scale were limiting factors. Significance was primarily obtained in severe AD.

Fezakinumab was well-tolerated, with sustained clinical improvements after last drug dosing.

IL-22 functions as both a proinflammatory cytokine and an anti-inflammatory cytokine in various inflammations, depending on the cellular and cytokine milieu. However, the roles of IL-22 in the regulation of allergic airway inflammation are still largely unknown.

We sought to determine whether IL-22 is involved in the regulation of allergic airway inflammation.

We examined IL-22 production and its cellular source at the site of antigen-induced airway inflammation in mice. We also examined the effect of IL-22 neutralization, as well as IL-22 administration, on antigen-induced airway inflammation. We finally examined the effect of IL-22 on IL-25 production from a lung epithelial cell line (MLE-15 cells).

Antigen inhalation induced IL-22 production in the airways of sensitized mice. CD4(+) T cells, but not other lymphocytes or innate cells, infiltrating in the airways produced IL-22, and one third of IL-22-producing CD4(+) T cells also produced IL-17A. The neutralization of IL-22 by anti-IL-22 antibody enhanced antigen-induced IL-13 production, eosinophil recruitment, and goblet cell hyperplasia in the airways. On the other hand, intranasal administration of recombinant IL-22 attenuated antigen-induced eosinophil recruitment into the airways. Moreover, anti-IL-22 antibody enhanced antigen-induced IL-25 production in the airways, and anti-IL-25 antibody reversed the enhancing effect of anti-IL-22 antibody on antigen-induced eosinophil recruitment into the airways. Finally, IL-22 inhibited IL-13-mediated enhancement of IL-25 expression in IL-1β- or LPS-stimulated MLE-15 cells.

IL-22 attenuates antigen-induced airway inflammation, possibly by inhibiting IL-25 production by lung epithelial cells.