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).
We confirm the previously described association of rs2066808 variant with psoriasis and PsA and we show evidence of an extended genomic region inside IL23A gene as carrier of true disease susceptibility factors.
IL-23 is important in the proliferation and maintenance of IL-17, and therefore, cytokines of the IL-23/IL-17 axis attracted much interest as therapeutic targets in psoriasis and PsA.
Psoriatic arthritis (PsA) can be treated using biologic therapies targeting biomolecules such as tumor necrosis factor alpha, interleukins (IL)-17 and IL-23.
The IL-23/IL-17 axis plays a critical pathogenic role for both PsA and Ps, and biologics neutralizing IL-17A or IL-23/IL-12 are effective therapies for PsA and Ps.
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.
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.
To investigate the levels of the proinflammatory cytokines tumor necrosis factor α (TNF-α), interleukin 23 (IL-23) and IL-17 in patients with psoriasis and psoriatic arthritis with concomitant metabolic syndrome.
Thus, these Ad.scIL-23-treated mice represent a physiologically relevant model of psoriatic arthritis for understanding disease progression and for testing therapeutic approaches.-Flores, R. R., Carbo, L., Kim, E., Van Meter, M., De Padilla, C. M. L., Zhao, J., Colangelo, D., Yousefzadeh, M. J., Angelini, L. A., Zhang, L., Pola, E., Vo, N., Evans, C. H., Gambotto, A., Niedernhofer, L. J., Robbins, P. D. Adenoviral gene transfer of a single-chain IL-23 induces psoriatic arthritis-like symptoms in NOD mice.
In recent years, interleukin (IL)-12/IL-23 inhibitors have entered clinical practice as a new class of drug for the treatment of PsA, with some data suggesting a lower effect of body weight on their effectiveness.
Furthermore, polymorphisms of <i>IL23R</i> are a risk factor for ankylosing spondylitis (AS) and psoriatic arthritis (PsA), which indicates that IL-23 is also involved in the pathogenesis of spondyloarthritis (SpA).
Interleukin-17A (IL-17A), IL-17F, IL-23, and CRP concentrations were measured in serum samples collected as part of the 2 PSUMMIT phase III studies of ustekinumab in PsA (n = 927).
Perturbation of the IL-23/Th17 axis instigates Th17-mediated inflammation in R26Stat3C<sup>stopfl/fl</sup> CD4Cre mice, leading to cutaneous and synovio-entheseal inflammation and bone pathologic features highly reminiscent of human PsA.
More recently, analysis of psoriasis genome-wide association studies in a PsA subgroup has also implicated IL23A, TNFAIP3, and TNIP1 genetic variants as conferring risk to PsA.
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).