Dupilumab induced ‘rapid and stable blockade’ of IL-4R alpha in B and T cells in AD

Dupilumab was associated with a rapid onset of action in B and T cells that persisted through a year of therapy in patients with atopic dermatitis, according to a study.

“Dupilumab, a mAb targeting IL-4 receptor alpha (IL-4R alpha), markedly improves disease severity in patients with atopic dermatitis,” Daphne S. Bakker, MD, of the National Expertise Center for Atopic Dermatitis and the department of dermatology and allergology at University Medical Center Utrecht, the Netherlands, and colleagues wrote.

The researchers suggested that the impact of blocking IL-4R alpha on the dynamics of circulating skin-homing T cells has not yet undergone investigation, noting that these T cells are critical in the pathologic mechanism of AD. In addition, they added that it is unclear if dupilumab has the capacity to induce long-lasting polarization in the T and B cells.

In the study of 10 patients with moderate to severe AD, both short- and long-term effects of the drug were assessed for a number of parameters, including “IL-4R alpha expression and T-cell cytokine production within total and skin-homing (cutaneous lymphocyte antigen⁺/CCR4⁺) subpopulations,” according to the study.

A complete blockade of IL-4R alpha expression and signal transducer and activator of transcription 6 phosphorylation in CD19⁺ B cells and CD4⁺ T cells was observed after treatment with dupilumab. This effect was observed within 2 hours of treatment initiation and persisted through 52 weeks of follow-up.

The drug failed to induce a change in the proportion of skin-homing T-cell subsets. However, a significant decrease in the percentage of proliferating (Ki67⁺) and T helper type 2 and T helper type 22 cytokine-producing skin-homing CD4⁺ T cells occurred after 4 weeks of treatment.

The researchers did not observe skewing in general T helper type cells, even after 52 weeks.

“Overall, this study confirms the mechanism of action of dupilumab treatment by demonstrating a (very) rapid and stable blockade of IL-4R alpha on B cells and T cells accompanied by a strong early functional immunological effect (after 4 weeks), specifically in skin-homing T cells of patients with AD treated with dupilumab,” the researchers wrote. “For the future, monitoring peripheral (skin-homing) T-cell responses might be a useful tool to predict and/or monitor treatment efficacy and potential side effects and guide tapering strategies in patients with AD.”