Background Atopic dermatitis (AD) is the most common inflammatory skin disease, but treatment options for moderate-to-severe disease are limited. Ustekinumab is an IL-12/IL-23p40 antagonist that suppresses Th1, Th17 and Th22 activation, commonly used for psoriasis patients. Objective We sought to assess efficacy and safety of ustekinumab in moderate-to-severe AD patients. Methods In this phase II, double-blind, placebo-controlled study, 33 patients with moderate-to-severe AD were randomly assigned to either ustekinumab (n=16) or placebo (n=17), with subsequent crossover at 16wks, and last dose at 32wks. Background therapy with mild topical steroids was allowed to promote retention. Study endpoints included clinical (SCORAD50) and biopsy-based measures of tissue structure and inflammation, using protein and gene expression studies. Results The ustekinumab group achieved higher SCORAD50 responses at 12wks, 16wks (the primary endpoint), and 20wks compared to placebo, but the difference between groups was not significant. The AD molecular profile/transcriptome showed early robust gene modulation, with sustained further improvements until 32wks in the initial ustekinumab-group. Distinct and more robust modulation of Th1, Th17 and Th22 but also Th2-related AD genes was seen after 4wks of ustekinumab treatment (i.e. MMP12, IL-22, IL-13, IFN-γ, elafin/PI3, CXCL1, CCL17; p<0.05). Epidermal responses (K16, terminal differentiation) showed faster (4wks) and long-term regulation (32wks) from baseline in the ustekinumab-group. No severe adverse events were observed. Conclusions Ustekinumab had clear clinical and molecular effects, but clinical outcomes might have been obscured by a profound “placebo” effect, most likely due to background topical glucocorticosteroids and possibly insufficient dosing for AD.

Petrolatum robustly modulates antimicrobials and epidermal differentiation barrier measures. These data shed light on the beneficial molecular responses of petrolatum in barrier-defective states, such as AD and postoperative wound care.

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