Testing Ustekinumab for Severe Atopic Dermatitis

Approved by the FDA to treat plaque psoriasis, psoriatic arthritis, and active Crohn's disease, ustekinumab appeared to benefit patients with severe atopic dermatitis (AD) in a small study seeking to correlate its immunologic effects with clinical efficacy.

Ustekinumab (Stelara, Janssen), a monoclonal antibody approved by the FDA to treat plaque psoriasis, psoriatic arthritis, and active Crohn's disease, appeared to benefit patients with severe atopic dermatitis (AD) in a small study seeking to correlate its immunologic effects with clinical efficacy.

The investigation of the effects of ustekinumab on epidermal hyperplasia, inflammatory infiltrate, and symptoms of AD was published online this month in the Journal of the American Academy of Dermatology.

EASI

Three patients with severe, therapy-resistant AD were enrolled to receive 45mg of subcutaneous ustekinumab at 0, 4, and 12 weeks and then every 8 weeks, with testing completed at 16 weeks. Changes in symptom severity were measured principally with the Eczema Area and Severity Index () and Scoring Atopic Dermatitis (SCORAD).

Skin biopsy features were compared from baseline to week 8 against control specimens from 5 healthy volunteers. Assessments included measuring messenger RNA levels of chemokines and cytokines involved in the particular T-cell pathways thought to contribute to cutaneous inflammatory responses of AD.

EASI

Christine Bangert and colleagues reported that all patients experienced a gradual improvement of symptoms, meeting the primary efficacy criteria of a 50 percent reduction in the score by week 16, as well as significant decrease in SCORAD index and on two measures of pruritus. Epidermal hyperproliferation and hyperplasia were reduced, but not to levels matching healthy skin controls.

Analysis of inflammatory infiltrate evidenced some degree of normalization, with a stable number of epidermal Langerhans cells throughout the treatment period corresponding to healthy skin controls. Inflammatory dendritic epidermal cells, which the investigators note are a hallmark of AD, were significantly reduced with treatment, as were dermal mast cells. T cells were clearly reduced with treatment, with mRNA measurements revealing reduction in gene expression levels of T-helper (Th) 2- and 22-related cytokines.

"It is conceivable that a modifying effect of ustekinumab on Th22-related pathways in chronic AD lesions results in a down-regulation of Th2-associated proinflammatory processes," Bangert and colleagues indicated. "Taken together, our results demonstrate a distinct clinical and immunologic response to ustekinumab in a small patient cohort."

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