There is an increased risk of opportunistic infections in patients with PsA, and this risk is increased further with targeted biologic therapy.<b>Areas covered</b>: This paper reviews the role of the interleukin (IL)-12, IL-23 and IL-17 axis in the pathogenesis of PsA.
IL-17A+ CD8+ T cells were predominantly TCRαβ+ and their frequencies were increased in the SF vs. PB of patients with established PsA (p<0.0001) or other SpA (p=0.0009).
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.
Since the connection of dysregulated IL-17 and psoriasis pathogenesis turned out to be particularly evident, a number of monoclonal antibodies targeting IL-17 pathways have been approved and are used as first line treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis, and further agents are currently in clinical development.
Despite a ballooning therapeutic tool box, treatment responses to newer biologic agents and oral small molecules in psoriatic arthritis (PsA) and spondyloarthritis (SpA) are of similar magnitude to those observed with anti-Tumor Necrosis Factor (TNF) medications (1, 2).The PsA and SpA therapeutic outcomes stand in marked contrast to those reported in psoriasis where blockade of molecules in the IL-23/IL-17 pathway often provide prolonged, deep responses and in some cases even remission (3).
These results suggest that Breg cells are a major target of apremilast in PsA and psoriasis and that apremilast-induced increase of Breg cells is associated with a decrease of Th1 cells, IFNγ-producing NKT cells and IL-17-producing NKT cells.
The guideline covers the management of active PsA in patients who are treatment-naive and those who continue to have active PsA despite treatment, and addresses the use of oral small molecules, tumor necrosis factor inhibitors, interleukin-12/23 inhibitors (IL-12/23i), IL-17 inhibitors, CTLA4-Ig (abatacept), and a JAK inhibitor (tofacitinib).
The guideline covers the management of active PsA in patients who are treatment-naive and those who continue to have active PsA despite treatment, and addresses the use of oral small molecules, tumor necrosis factor inhibitors, interleukin-12/23 inhibitors (IL-12/23i), IL-17 inhibitors, CTLA4-Ig (abatacept), and a JAK inhibitor (tofacitinib).
83 records were enrolled.The IL-17 level was elevated in AS (SMD = 2.348, P < .001), RA (SMD = 1.502, P < .001), PsA (SMD = 1.710, P < .001) and OA (SMD = 1.192, P = .016), and similar results occurred in subgroup analysis.
Two independent authors searched the databases PubMed and EMBASE for studies reporting on adverse events in phase 3 trials of IL-17 and IL-23 inhibitors for patients with psoriasis and psoriatic arthritis.
In this review, we focus on the latest data from studies investigating the role of IL-17A in ankylosing spondylitis (AS) and PsA that build on existing and emerging scientific knowledge in the field.
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.
Cytokines from the IL-17 family have been shown to be involved in the pathogenesis of several diseases such as spondyloarthritis, psoriatic arthritis, or psoriasis.
Intriguingly, although targeting the IL-23-IL-17 axis substantially improves psoriasis outcomes, this strategy is not more effective than TNF inhibitors in improving musculoskeletal symptoms in PsA.
IL-17A is classically considered to be the most biologically active, but recent studies have shown that IL-17F is also increased in psoriatic skin and synovial cell in psoriatic arthritis, supporting the rationale for targeting both IL-17A and IL-17F in psoriatic disease.
In the circulation, we found increased percentage of CD8<sup>+</sup> CCR6<sup>+</sup> T cell effectors expressing CD69 and of IL-17-producing T cells in patients with psoriatic arthritis.
Therapeutic agents targeting the IL-23/IL-17 axis have been proven to be very effective in psoriasis and PsA, some are already in the therapeutic armamentarium and others are in the development.
Although the short-term effects of tumor necrosis factor alpha (TNF-α) and interleukin-17A (IL-17A) inhibition on the structural changes in psoriatic arthritis (PsA) using high-resolution peripheral quantitative computed tomography (HR-pQCT) have been reported, no studies have investigated the long-term structural changes in PsA patients receiving routine care.