In the last years TRAF3IP2 gene variants had been described as associated with susceptibility to several diseases such as psoriasis and psoriatic arthritis.
TRAF3IP2 gene, associated with susceptibility to psoriatic arthritis and psoriasis, encodes for Act1, a negative regulator of adaptive immunity and a positive signaling adaptor in IL-17-mediated immune responses.
The recent observations described and discussed in this review raise the clinically significant possibility of redefining the immunological role of IL-17 in PsA and provide a basis for defining future studies to elucidate the molecular and cellular functions of Act1.
Only three modestly sized genome-wide association studies of PsA have been undertaken to date, but they have identified the HLA-C region, IL12B, TRAF3IP2, and FBXL19 genes as being associated with PsA susceptibility.
Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6, suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV.
A stratified analysis of our datasets including only PsA cases (1,922 cases compared to 8,037 controls, P = 4.57 × 10⁻¹² for rs33980500) suggested that TRAF3IP2 represents a shared susceptibility for PsV and PsA.
To examine whether initiation of interleukin (IL)-17, IL-12/23 or tumour necrosis factor (TNF) inhibitor is associated with an increased risk of serious infection among real-world psoriasis (PsO) or psoriatic arthritis (PsA) patients.
Anti-tumor necrosis factor-alpha (TNF-α) immunotherapy has revolutionized the treatment of inflammatory diseases, such as psoriasis and psoriatic arthritis.
Fecal samples from PsA/SpA patients pre- and post-treatment with tumor necrosis factor inhibitors (TNFi; n=15) or an anti-interleukin (IL)-17A monoclonal antibody inhibitor (IL-17i; n=14) underwent sequencing (16S, ITS and shotgun metagenomics) and computational microbiome analysis.
Biologic agents with different mechanisms of action [inhibitors of tumor necrosis factor-α (TNF-α), interleukin (IL)-12/23, and IL-17] showed efficacy in randomized controlled trials (RCT) in the treatment of psoriatic arthritis.
HLA-C*06:02-negative patients were significantly more likely to respond to adalimumab than ustekinumab at all time points (most strongly at 6 months: odds ratio [OR], 2.95; P = 5.85 × 10<sup>-7</sup>), and the difference was greater in HLA-C*06:02-negative patients with psoriatic arthritis (OR, 5.98; P = 6.89 × 10<sup>-5</sup>).
We also explore the role of MTX in combination therapy with tumor necrosis factor inhibitors, in addition to its safety and tolerability, to answer the question: should methotrexate have any place in the treatment of psoriatic arthritis?
Data were pooled from 2 phase III studies (Efficacy and Safety of Tofacitinib in Psoriatic Arthritis [OPAL Broaden] and Tofacitinib in Patients with Psoriatic Arthritis With Inadequate Response to TNF Inhibitors [OPAL Beyond]) and 1 ongoing long-term extension (Open-Label Extension Study of Tofacitinib in Psoriatic Arthritis [OPAL Balance], data cutoff January 2017; database not locked).
Real-World Long-Term Effectiveness of Tumor Necrosis Factor Inhibitors in Psoriatic Arthritis Patients from the Rheumatic Diseases Portuguese Register.
Achieving remission in psoriatic arthritis by early initiation of TNF inhibition: a double-blind, randomised, placebo-controlled trial of golimumab plus methotrexate versus placebo plus methotrexate.
Despite the introduction of new molecules with different mechanisms of action, the role of anti-TNF in the treatment of all disease manifestations of this intriguing disease is still central.<b>Areas covered</b>: The aim of this paper is to review the role of anti-TNF drugs in the treatment of different disease domains in PsA (peripheral and axial joints, skin, enthesis, patient's reported outcomes, extra-articular manifestations), reporting data from randomized clinical trials and observational studies.
To evaluate the risk of AF and major adverse cardiovascular events (MACE) associated with use of ustekinumab vs tumor necrosis factor inhibitors (TNFi) in patients with psoriasis or psoriatic arthritis.
Persistence of tumor necrosis factor inhibitor or conventional synthetic disease-modifying antirheumatic drug monotherapy or combination therapy in psoriatic arthritis in a real-world setting.
Clinical trials have reported the effectiveness of numerous biologics with different targets, such as tumor necrosis factor-α, interleukin (IL)-17A, IL-17 receptor, IL-12/23(p40), and IL-23(p19) for the treatment of PsA.
Trajectory of radiographic change over a decade: the effect of transition from conventional synthetic disease-modifying antirheumatic drugs to anti-tumour necrosis factor in patients with psoriatic arthritis.
The association to PsA was observed in the presence of polymorphisms: TNF-238 G > A (rs361525), -308 G > A (rs1800629), and -857 C > T (rs1799724); IL12B C > G (rs6887695) and A > C (rs3212227); IL23A A > G (rs2066808) and IL23R G > A (rs11209026).
If TNF inhibitors are initiated in the early stages of psoriatic arthritis, this could potentially modulate disease and therefore allow us to discontinue the TNF inhibitor after achieving remission.
Patients with PsA enrolled in the Corrona Registry between 2005 and 2013 were followed from initiation of a TNF inhibitor (TNFi; etanercept, adalimumab, infliximab, certolizumab, or golimumab) to the visit closest to 12 months.
Improved knowledge of the immune/inflammatory pathways, which characterise the pathophysiology of rheumatoid arthritis (RA) and seronegative spondyloarthropathies (SpA), such as ankylosing spondylitis (AS) and psoriatic arthritis (PsA), have provided the link between inflammation and bone loss, via a complex network of bone cells, T and B cells, pro-inflammatory cytokines such as TNF-α, IL1, IL6, IL17, IL23, costimulator molecules, signalling pathways including both RANKL/RANK/OPG and Wnt signallings.