Adalimumab (antitumour necrosis factor-α) treatment of hidradenitis suppurativa ameliorates skin inflammation: an in situ and ex vivo study

Br J Dermatol. 2012 Feb;166(2):298-305. doi: 10.1111/j.1365-2133.2011.10698.x.

Abstract

Background: Hidradenitis suppurativa (HS) is a difficult-to-manage disease. Randomized controlled trials with antitumour necrosis factor (TNF)-α biologics have been conducted and in most studies disease activity was reduced. However, the mechanism of action in HS skin is so far unknown.

Objectives: To assess whether anti-TNF-α treatment affects in situ cytokine production and frequency of inflammatory cell populations in HS lesional skin.

Methods: Nine patients with HS, participating in a larger placebo-controlled, double-blind phase IIb clinical trial on the efficacy and safety of adalimumab in patients with moderate to severe HS (M10-467), were randomized and treated for 16weeks. In a mechanism-of-action substudy, biopsies were obtained at fixed time points pre- and post-treatment. One part of the biopsy was cultured for 24h for cytokine release in the culture medium, while another part was used for in situ analysis.

Results: Secretion of cytokines, including interleukin (IL)-1β, CXCL9 [monokine induced by interferon-γ (MIG)], IL-10, IL-11, B-lymphocyte chemoattractant (BLC) and IL-17A, was significantly elevated in HS. Adalimumab treatment was associated with decreased production of cytokines in HS skin, especially IL-1β, CXCL9 (MIG) and BLC. Treatment significantly reduced the number of CD11c+,CD14+ and CD68+ cells in HS lesional skin. The numbers of CD3+ and CD4+ T cells, and CD20+ and CD138+ B cells were also reduced by adalimumab treatment.

Conclusions: Adalimumab treatment inhibits important cytokines and inflammatory cell numbers in lesional HS skin, especially levels of IL-1β and numbers of inflammatory CD11c+ dendritic cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab
  • Adult
  • Aged
  • Anti-Inflammatory Agents / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Cells, Cultured
  • Cytokines / metabolism
  • Dermatitis / drug therapy*
  • Female
  • Hidradenitis Suppurativa / drug therapy*
  • Hidradenitis Suppurativa / metabolism
  • Humans
  • Male
  • Middle Aged
  • Skin / metabolism
  • Treatment Outcome
  • Young Adult

Substances

  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal, Humanized
  • Cytokines
  • Adalimumab