Evidence for tmTNF reverse signaling : Implications for an arginase-1-mediated therapeutic effect of TNF inhibitors during inflammation.

In order to ascertain the significance of transmembrane tumor necrosis factor (tmTNF) reverse signaling , we generated a triple transgenic mouse model (3TG, TNFR1-/-, TNFR2-/-, and tmTNFKI/KI) in which all canonical tumor necrosis factor (TNF) signaling was abolished. In bone-marrow-derived macrophages harvested from these mice, various anti-TNF biologics induced the expression of genes characteristic of alternative macrophages and also inhibited the expression of pro-inflammatory cytokines mainly through the upregulation of arginase-1. Injections of TNF inhibitors during arthritis increased pro-resolutive markers in bone marrow precursors and joint cells leading to a decrease in arthritis score.

Biological DMARD efficacy in psoriatic arthritis: a systematic literature review and meta-analysis on articular, enthesitis, dactylitis, skin and functional outcomes.

Objectives: There is no hierarchy in the use of biotherapies (bDMARDs) in psoriatic arthritis (PsA) and no published head-to-head comparative studies. Our purpose is to evaluate the respective efficacy of TNF inhibitors, IL12/23 inhibitors (ustekinumab), IL17 inhibitors (secukinumab, ixekizumab) and CTLA4Ig (abatacept) on articular, enthesitis, dactylitis, skin and functional outcomes in PsA.

Methods: Randomised controlled trials assessing bDMARDs in PsA were selected through the MedLine, Cochrane and Embase databases.