Mini Review: New Treatments in Psoriatic Arthritis. Focus on the IL-23/17 Axis

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.

Neutrophilic asthma: welcome back!

“…What does this mean for targeted therapy of neutrophilic asthma? Brodalumab is a human anti-IL-17 receptor A mAb that inhibits IL-17A and IL-17F [15]. It is effective in psoriasis, but a trial in asthma was negative [5].…”

Practical recommendations for systemic treatment in psoriasis in case of coexisting inflammatory, neurologic, infectious or malignant disorders (BETA‐PSO: Belgian Evidence‐based Treatment Advice in Psoriasis; part 2)

“…It is our expert opinion that other biologics including guselkumab, risankizumab, tildrakizumab and brodalumab are also effective treatment in psoriatic patients with PSA, although they are currently unlicensed in this indication. 11 Systemic treatment with cyclosporine, for psoriasis patients with PSA, is less advisable due to limited evidence. Nonetheless, some studies support beneficial effects of cyclosporine on the symptoms of PSA in patients with skin psoriasis.…”

Pathogenesis of psoriasis in the “omic” era. Part IV. Epidemiology, genetics, immunopathogenesis, clinical manifestation and treatment of psoriatic arthritis

“…The striking features of PsA are subchondral perientheseal edema and diffuse bone edema [ 36 ]. The subenthesis bone in PsA represents increased vascularity and hyperosteoclastic cystic and erosive changes [ 42 ]. Physiologically, bone homeostasis is maintained by the balance between osteoclasts, capable of bone resorption, and osteoblasts, responsible for bone formation.…”

“…In PsA, IL-22 promotes the proliferation of the human mesenchymal stem cells (MSCs) and their differentiation into osteoblasts [ 30 ]. It induces osteoproliferation in the enthesis and periosteum via the STAT3 activation on osteoblasts causing new bone formation manifested by the peripheral joint fusion, enthesophytes, spurs, ankylosis as well as syndesmophytes in the axial skeleton and changes in the sacroiliac joints [ 28 , 42 , 41 ]. Mechanisms responsible for new bone formation in PsA may result from activation of several signaling pathways, including Wnt (Wingless-type like signaling), BMP (bone morphogenetic protein) and the Hedgehog signaling pathway.…”