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New insights into the pathogenesis and genetics of psoriatic arthritis.

ABSTRACT: Psoriasis vulgaris and psoriatic arthritis (PsA) are inter-related heritable diseases. Psoriatic skin is characterized by hyperproliferative, poorly differentiated keratinocytes and severe inflammation. Psoriatic joints are characterized by highly inflamed synovia and entheses with focal erosions of cartilage and bone. Genetic analyses have uncovered risk factors shared by both psoriasis and PsA. Predisposition to psoriasis and PsA arising from common variation is most strongly conferred by the HLA class I region. Other genetic risk factors implicate the interleukin (IL)-23 pathway and the induction and regulation of type 17 T-helper cells in the pathogenesis of both diseases. Secretion of cytokines, such as IL-22 and IL-17, could result in the hyperproliferative phenotype of keratinocytes and potentially synoviocytes, leading to a vicious cycle of cellular proliferation and inflammation in both the skin and joints. In synovial tissue, disease-related cytokines could also promote osteoclast formation, resulting in bone erosion. The next step will be to identify genetic risk factors specifically associated with PsA. Although therapies that target tumor necrosis factor are often highly successful in the treatment of both diseases, genetic findings are likely to lead to the development of treatments tailored to an individual's genetic profile.

SUBMITTER: Nograles KE

PROVIDER: S-EPMC2790861 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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New insights into the pathogenesis and genetics of psoriatic arthritis.

Nograles Kristine E KE Brasington Richard D RD Bowcock Anne M AM

Nature clinical practice. Rheumatology 20090201 2

Psoriasis vulgaris and psoriatic arthritis (PsA) are inter-related heritable diseases. Psoriatic skin is characterized by hyperproliferative, poorly differentiated keratinocytes and severe inflammation. Psoriatic joints are characterized by highly inflamed synovia and entheses with focal erosions of cartilage and bone. Genetic analyses have uncovered risk factors shared by both psoriasis and PsA. Predisposition to psoriasis and PsA arising from common variation is most strongly conferred by the ...[more]

PMID: 19182814

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Project description:IntroductionPsoriatic arthritis (PsA) is an immune-mediated chronic inflammatory arthropathy associated with impaired physical function and reduced quality of life. Biologic therapies that target tumor necrosis factor (anti-TNF) have significantly improved clinical outcomes. Partial, non- and transient responses remain common comprising significant unmet clinical need. New therapies with novel modes of action are urgently required.ObjectivesThe interleukin (IL)-17 pathway has recently been attributed a critical role in the pathogenesis of spondyloarthritides. Herein, we review data from clinical studies with secukinumab, a novel fully human IgG1κ anti-IL-17A monoclonal antibody (mAb), in patients with active PsA.ResultsAcross two pivotal phase 3 studies, secukinumab provided significant and sustained reductions in the signs and symptoms of PsA, inhibition of radiographic progression, and improved patient-reported outcomes and measures of quality of life. The primary efficacy endpoint, a ≥20% improvement from baseline according to the American College of Rheumatology 20 (ACR20) response at Week 24, was significantly higher in patients treated with secukinumab compared with placebo, with improvements sustained through at least 52 weeks. Clinical benefits were seen with secukinumab regardless of concomitant methotrexate treatment and in patients who were either anti-TNF-naïve or who were inadequate responders to anti-TNF therapy. Secukinumab was well-tolerated, with a safety profile consistent with that previously reported in psoriasis trials. The most common adverse events were nasopharyngitis, upper respiratory tract infections, and headache.ConclusionSecukinumab offers an effective new addition to the available treatment options for PsA. Regulatory submissions have been filed worldwide, with the first approvals recently obtained in Japan and Europe. Future studies are required to define the optimal timing and strategic use of this novel treatment modality.FundingNovartis Pharma.

Dataset Information

New insights into the pathogenesis and genetics of psoriatic arthritis.

Publications

New insights into the pathogenesis and genetics of psoriatic arthritis.

Similar Datasets

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