Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Volume 141, Issue 11, Pages 2730-+Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jid.2021.04.010
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- AbbVie
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The study suggests that ADA has a distinct mechanism of action in hidradenitis suppurativa compared to other drugs, promoting wound healing and specific regulation of inflammatory M phi. ADA treatment significantly reduces levels of inflammatory MMPs and promotes the expression of healing-related MMPs and tissue inhibitor of metalloproteinases in patients with hidradenitis suppurativa who responded to the therapy.
Adalimumab (ADA) is the only Food and Drug Administration-approved treatment for moderate-to-severe hidradenitis suppurativa, whereas etanercept and certolizumab-pegol have been shown to be ineffective, suggesting that the mechanism of action of ADA is distinct in hidradenitis suppurativa and may contribute to improved wound healing. Given that macrophages (M phi s) play pivotal roles throughout the wound healing process, an in vitro M phi differentiation assay was carried out to assess the impact of TNF-anti-TNF complexes on these cells. TNF-ADA complexes exhibited stronger inhibitory effects on inflammatory M phi differentiation. Moreover, RNA sequencing revealed several unique wound healing profiles for TNF-ADA-treated inflammatory M phi s, which were not observed for those treated with either TNF-etanercept or TNF-certolizumab-pegol complexes, including the inhibition of the matrix metalloproteinase (MMP) pathway. In addition, ADA administration was found to significantly reduce the levels of inflammatory MMP-1 and MMP-9 while promoting wound-healing MMP-13 and tissue inhibitor of metalloproteinases 2 levels in the circulation of the patients with hidradenitis suppurativa who responded to treatment. Our in vitro findings show that TNF-ADA-treated inflammatory M phi s exhibit a distinct profile resembling wound healing. Moreover, ADA not only differentially regulates MMP expression in patients with hidradenitis suppurativa responding to the therapy but also potentially induces a transition to a profile suggestive of wound healing.
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