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

TNF-alpha has a central role in the development and maintenance of psoriatic plaques, and its serum levels correlate with disease activity. Anti-TNF-alpha drugs are, however, ineffective in a relevant percentage of patients for reasons that are currently unknown. To understand whether the response to anti-TNF-alpha drugs is influenced by the production of anti-drug antibodies or by the modulation of the TNF alpha-TNF alpha 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-alpha therapies (adalimumab, etanercept or infliximab), and measured plasma levels of TNF-alpha, TNF-alpha soluble receptors, drug and anti-drug antibodies. Moreover, we analyzed the production of TNF-alpha and TNF-alpha 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-alpha 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-alpha and sTNFRII in vitro than patients responding to infliximab; v) PBMCs from patients not responding to infliximab produce higher levels of TNF-alpha and sTNFRII than patients responding to infliximab; vi) anti-TNF-alpha drugs significantly altered monocyte subsets. A complex remodelling of the TNF alpha-TNF alpha receptor system thus takes place in patients treated with anti-TNF-alpha drugs, that involves either the production of anti-drug antibodies or the modulation of monocyte phenotype or inflammatory activity.