Adalimumab (anti-TNF-alpha) treatment of hidradenitis suppurativa ameliorates skin inflammation: an in situ and ex vivo study.
Author(s): van der Zee HH, Laman JD, de Ruiter L, Dik WA, Prens EP
Affiliation(s): Departments of Dermatology Immunology, Erasmus MC, University Medical Center, Rotterdam.
Publication date & source: 2011-10-20, Br J Dermatol., [Epub ahead of print]
Background: Hidradenitis suppurativa (HS) is a difficult to manage disease. Randomized controlled trials with anti-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 HS patients, 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 sub-study, 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 IL-1beta, CXCL9 (MIG), IL-10, IL-11, BLC and IL-17A was significantly elevated in HS. Adalimumab treatment was associated with decreased cytokine production in HS skin, especially IL-1beta, 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, 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 inflammatory CD11c+ dendritic cells and.IL-1beta levels. Copyright (c) 2011 British Association of Dermatologists.