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


OBJECTIVE
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.
Departments of Dermatology Immunology, Erasmus MC, University Medical Center, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. h.vanderzee@erasmusmc.nl
H H
HH
van der Zee
J D
JD
Laman
L
L
de Ruiter
W A
WA
Dik
E P
EP
Prens
D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003872:Dermatitis / Q000188:drug therapy*; D005260:Female; D017497:Hidradenitis Suppurativa / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult
D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; D000068879:Adalimumab