Abstract
Psoriasis, an inflammatory skin disease, and psoriatic arthritis (PsA), an inflammatory arthritis, share clinical, genetic, and pathogenic factors and may be summed as one disease, the psoriatic disease. Interleukin (IL)-17 plays a major role in the development of both psoriasis and PsA. 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. 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. Some agents, target IL-23 and others IL-17 and include anti-IL-12/IL-23 p40 (ustekinumab, briankizumab), anti-IL-23p19 (guselkumab, tildrakizumab, risankizumab, brazikumab, mirikizumab), anti-IL-17A (secukinumab, ixekizumab), dual anti-IL-17A and anti-IL-17F (bimekizumab), or anti-IL-17 receptor (brodalumab) monoclonal antibodies. Janus tyrosine kinase(JAK) inhibitors also directly affect IL-23 and, thus, IL-17. After the first-generation pan-JAK inhibitors have been shown efficacy (tofacitinib, baricitinib), new-generation selective JAK inhibitors (filgotinib, upadacitinib) are under investigation in psoriasis and PsA.
Highlights
Psoriatic arthritis (PsA) is an inflammatory joint disease associated with psoriasis, a common inflammatory skin disease with a prevalence 2% to 3% worldwide (Rachakonda et al, 2014)
PsA occurs in a third of the patients with psoriasis (Mease et al, 2013) and apart from psoriasis, manifests with peripheral arthritis, enthesitis, dactylitis, spine involvement, and uveitis
The presence of enthesitis, which may be subclinical is very common in psoriasis and substantially increase the frequency of PsA in patients with psoriasis (Sakkas et al, 2019; Mease et al, 2019b) The pathogeneses of both PsA and psoriasis are incompletely understood, but innate and adaptive cells and proinflammatory cytokines are involved, the interleukin(IL)-23/IL-17 axis (Sakkas and Bogdanos, 2017)
Summary
Psoriatic arthritis (PsA) is an inflammatory joint disease associated with psoriasis, a common inflammatory skin disease with a prevalence 2% to 3% worldwide (Rachakonda et al, 2014). IL-17-producing T (Th17) cells are major players in the pathogenesis of psoriasis because they are present in psoriatic lesions and can induce activation/proliferation of keratinocytes and endothelial cells (Lowes et al, 2013; Skepner et al, 2014; Sakkas and Bogdanos, 2017; Boutet et al, 2018). A mice model with T cell-specific hyperactive STAT3 has augmented Th17 response and exhibits epidermal proliferation and synovial-entheseal inflammation which improve by abrogation of IL-17 and IL-22 cytokines (Yang et al, 2018). IL-17- and IL-22-producing cells are present with different frequencies in various anatomical sites with IL-22 expression being very low in arthritic joints in PsA (Benham et al, 2013). Briakinumab at week 12 achieved PASI75 in ~90% of patients versus 3% in the placebo group, but caused adverse effects in 36% of patients versus 10% in the placebo group (Kimball et al, 2008)
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