Ustekinumab treatment in severe atopic dermatitis: Down-regulation of T-helper 2/22 expression

J Am Acad Dermatol. 2017 Jan;76(1):91-97.e3. doi: 10.1016/j.jaad.2016.07.047. Epub 2016 Oct 13.

Abstract

Background: It has recently been suggested that patients with moderate to severe atopic dermatitis (AD) may profit from anti-interleukin (IL)-12/-23 p40 therapy.

Objective: We sought to assess the immunologic effects of ustekinumab treatment on AD skin and to correlate them with the clinical efficacy of this drug.

Methods: We investigated the course of 3 patients with severe AD who were administered 45 mg of subcutaneous ustekinumab over a period of 16 weeks. Clinical scores and skin biopsy specimens, taken at baseline and at week 8, were used to assess changes in disease severity.

Results: All patients showed a gradual improvement of the disease, achieving a 50% reduction in the Eczema Area and Severity Index score by week 16. Immunohistology of skin biopsy specimens revealed a significant decrease in the degree of epidermal hyperplasia/proliferation and the number of infiltrating dermal T cells, dendritic cells, and mast cells after treatment. Using quantitative real-time polymerase chain reaction of lesional skin, we found a clear reduction of T-helper 2-/22-associated molecules after therapy.

Limitations: The small number of patients (n = 3) limits efficacy analysis and warrants prospective placebo-controlled studies in larger patient cohorts.

Conclusion: Blocking IL-12/-23 p40 could be beneficial for a subgroup of patients with severely infiltrated AD.

Keywords: T helper 17; T helper 2; T helper 22; anti-interleukin-12/-23 p40; atopic dermatitis; cytokines; eczema; inflammatory; ustekinumab.

MeSH terms

  • Adult
  • CD4 Lymphocyte Count
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dermatitis, Atopic / drug therapy*
  • Dermatitis, Atopic / pathology*
  • Dermatologic Agents / pharmacology*
  • Dermatologic Agents / therapeutic use
  • Down-Regulation / drug effects*
  • Female
  • Gene Expression / drug effects
  • Humans
  • Langerhans Cells / drug effects
  • Male
  • Mast Cells / drug effects
  • Middle Aged
  • RNA, Messenger / metabolism
  • Severity of Illness Index
  • T-Lymphocytes, Cytotoxic / drug effects
  • Th1 Cells / metabolism
  • Th17 Cells / metabolism
  • Th2 Cells / drug effects
  • Th2 Cells / metabolism*
  • Ustekinumab / pharmacokinetics*
  • Ustekinumab / therapeutic use

Substances

  • Cytokines
  • Dermatologic Agents
  • RNA, Messenger
  • Ustekinumab