Anti-TNF-α Drugs Differently Affect the TNFα-sTNFR System and Monocyte Subsets in Patients with Psoriasis

Abstract

TNF-α has a central role in the development and maintenance of psoriatic plaques, and its serum levels correlate with disease activity. Anti-TNF-α drugs are, however, ineffective in a relevant percentage of patients for reasons that are currently unknown. To understand whether the response to anti-TNF-α drugs is influenced by the production of anti-drug antibodies or by the modulation of the TNFα-TNFα receptor system, and to identify changes in monocyte phenotype and activity, we analysed 119 psoriatic patients who either responded or did not respond to different anti-TNF-α therapies (adalimumab, etanercept or infliximab), and measured plasma levels of TNF-α, TNF-α soluble receptors, drug and anti-drug antibodies. Moreover, we analyzed the production of TNF-α and TNF-α soluble receptors by peripheral blood mononuclear cells (PBMCs), and characterized different monocyte populations. We found that: i) the drug levels varied between responders and non-responders; ii) anti-infliximab antibodies were present in 15% of infliximab-treated patients, while anti-etanercept or anti-adalimumab antibodies were never detected; iii) plasma TNF-α levels were higher in patients treated with etanercept compared to patients treated with adalimumab or infliximab; iv) PBMCs from patients responding to adalimumab and etanercept produced more TNF-α and sTNFRII in vitro than patients responding to infliximab; v) PBMCs from patients not responding to infliximab produce higher levels of TNF-α and sTNFRII than patients responding to infliximab; vi) anti- TNF-α drugs significantly altered monocyte subsets. A complex remodelling of the TNFα-TNFα receptor system thus takes place in patients treated with anti-TNF-α drugs, that involves either the production of anti-drug antibodies or the modulation of monocyte phenotype or inflammatory activity.

Insensitivity versus poor response to tumour necrosis factor inhibitors in rheumatoid arthritis: a retrospective cohort study

“…However, whether this explains the refractory status and/or exacerbation of symptoms during treatment remains uncertain. Second, previous reports suggested that the effect of TNFis is related to monocytes [29,30]. For example, a TNFi was reported to increase the secretion of the soluble TNF receptor, a natural inhibitor of TNF, and production of interleukin 10 by monocytes [31].…”

Gene Expression of Tumor Necrosis Factor-Alpha in Etanercept-Treated Rheumatoid Arthritis Patients

“…The therapeutic efficacy of etanercept was reduced in CIA mice that developed anti-etanercept antibodies, and the authors concluded that these antibodies can considerably reduce the effects of etanercept (anti-arthritic and anti-osteoporotic effects) [18]. Therefore, the formation of anti-etanercept antibodies may interfere with the expression of TNF mRNA, but such subject is a matter of controversy, and more recently, anti-etanercept antibodies have not been detected in psoriatic patients treated with etanercept [19].…”

Effects of aloe polysaccharide, a polysaccharide extracted from Aloe�vera, on TNF‑α‑induced HaCaT cell proliferation and the underlying mechanism in psoriasis

“…In patients with psoriasis, the serum levels of TNF-α are associated with disease activity. During the development of psoriasis, TNF-α is secreted by T cells and has an important role in the pathogenic process (13). Despite previous studies suggesting that Aloe vera may represent a promising therapeutic agent for the treatment of patients with psoriasis (6,14,15).…”