Abstract
Psoriasis is a chronic systemic inflammatory disease causing erythematosus and scaly skin plaques; up to 30% of patients with psoriasis develop Psoriatic Arthritis (PsA), which is characterised by inflammation and progressive damage of the peripheral joints and/or the spine and/or the entheses. The pathogenic mechanisms driving the skin disorder in psoriasis and the joint disease in PsA are sustained by the activation of inflammatory pathways that can be overlapping, but also, at least partially, distinct. Cytokines members of the IL-23/IL-17 family, critical in the development of autoimmunity, are abundantly expressed within the cutaneous lesions but also seem to be involved in chronic inflammation and damage of the synovium though, as it will be here discussed, not in all patients. In this review, we will focus on the state of the art of the molecular features of psoriatic skin and joints, focusing on the specific role of the IL-23/IL-17 pathway in each of these anatomical districts. We will then offer an overview of the approved and in-development biologics targeting this axis, emphasising how the availability of the “target” in the diseased tissues could provide a plausible explanation for the heterogeneous clinical efficacy of these drugs, thus opening future perspective of personalised therapies.
Highlights
Psoriasis (Ps) is a systemic disease that affects around 1% of the population worldwide [1] causing chronic inflammation of the skin
In the absence of specific diagnostic criteria, the diagnosis of Psoriatic Arthritis (PsA), in the context of clinical trials, relies on the classification criteria published by the CASPAR (ClASsification criteria for Psoriatic ARthritis) group, which include: (i) evidence of psoriasis; (ii) psoriatic nail dystrophy; (iii) negative tests for rheumatoid arthritis (RA); (iv) dactylitis; and (v) radiographic evidence of juxta-articular new bone formation [7]
Better efficacy was demonstrated by the significantly higher proportion of patients achieving a 90% reduction in the Psoriasis Area and Severity Index (PASI) score at 12 weeks when treated with risankizumab (77%) compared to ustekinumab (40%), maintaining a similar safety profile [114]
Summary
Psoriasis (Ps) is a systemic disease that affects around 1% of the population worldwide [1] causing chronic inflammation of the skin. Targeting the IL-23/IL-17 axis has been shown to be a winning strategy in both Ps and PsA, as demonstrated by the clinical efficacy of the antagonists currently in use and by the ongoing development of new agents It is important, to note the discordant effectiveness between skin and joint disease at least in a sizable number of patients. We will provide an update of the recent advances in the understanding of Ps/PsA pathophysiology, including the tissue-dependent selective role of the IL-23/IL-17 axis, and the latest knowledge about approved and in-trial therapeutics targeting this pathway Both Ps and PsA are chronic multifactorial diseases driven by a complex interplay between genetic factors, environment and immune dysfunction. We will review and highlight their similarities and differences with regards to pathogenesis, metabolic biomarkers and histological features
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