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

作者：van der Zee H H^*; Laman J D; de Ruiter L; Dik W A; Prens E P

来源：British Journal of Dermatology, 2012, 166(2): 298-305.

DOI：10.1111/j.1365-2133.2011.10698.x

Background Hidradenitis suppurativa (HS) is a difficult-to-manage disease. Randomized controlled trials with antitumour necrosis factor (TNF)-alpha 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-alpha 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 16 weeks. 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 24 h for cytokine release in the culture medium, while another part was used for in situ analysis.
Results Secretion of cytokines, including interleukin (IL)-1 beta, CXCL9 [monokine induced by interferon-gamma (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-1 beta, 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-1 beta and numbers of inflammatory CD11c+ dendritic cells.

• 出版日期2012-2