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      Resolution of synovitis and arrest of catabolic and anabolic bone changes in patients with psoriatic arthritis by IL-17A blockade with secukinumab: results from the prospective PSARTROS study

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          Abstract

          Background

          Although the effects of interleukin-17A (IL-17A) inhibition on the signs and symptoms of psoriatic arthritis (PsA) are well defined, little is known about its impact of local inflammatory and structural changes in the joints. The PSARTROS study was designed to elucidate the effects of IL-17A inhibition on inflammation and bone changes in joints affected by PsA.

          Methods

          This was a prospective open-label study in 20 patients with active PsA receiving 24 weeks of treatment with the IL-17A inhibitor secukinumab. Magnetic resonance imaging (MRI), power Doppler ultrasound (PDUS), and high-resolution peripheral quantitative computer tomography (HR-pQCT) of the hands were performed at baseline and after 24 weeks to assess synovitis, periarticular inflammation, bone erosion, enthesiophyte formation, and bone structure. Demographic and clinical measures of joint disease (DAPSA and DAS28-ESR), skin disease (PASI and BSA), and composite measures (minimal disease activity, or MDA) were also recorded.

          Results

          Treatment with secukinumab led to significant improvement of signs and symptoms of PsA; 46% reached MDA and 52% DAPSA low disease activity. MRI synovitis ( P = 0.034) and signal in PDUS ( P = 0.030) significantly decreased after 24 weeks of treatment. Bone erosions in MRI and HR-pQCT and enthesiophytes in the HR-pQCT did not show any progression, and structural integrity and functional bone strength remained stable.

          Conclusions

          IL-17 inhibition by secukinumab over 24 weeks led to a significant decrease of synovial inflammation and no progression of catabolic and anabolic bone changes in the joints of patients with PsA.

          Trial registration

          ClinicalTrials.gov Identifier: NCT02483234, June 26, 2015; retrospectively registered.

          Electronic supplementary material

          The online version of this article (10.1186/s13075-018-1653-5) contains supplementary material, which is available to authorized users.

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          Most cited references 33

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          Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease.

          To characterize the diversity and taxonomic relative abundance of the gut microbiota in patients with never-treated, recent-onset psoriatic arthritis (PsA).
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            Blocking of interleukin-17 during reactivation of experimental arthritis prevents joint inflammation and bone erosion by decreasing RANKL and interleukin-1.

            Rheumatoid arthritis is characterized by an intermittent course of disease with alternate periods of remission and relapse. T cells, and in particular the T-cell cytokine interleukin-17 (IL-17), are expected to be involved in arthritic flares. Here, we report that neutralizing endogenous IL-17 during reactivation of antigen-induced arthritis prevents joint inflammation and bone erosion. Synovial IL-17 mRNA expression was clearly up-regulated during primary arthritis and was further enhanced after antigen rechallenge. Neutralization of IL-17 significantly prevented joint swelling at day 1 of flare and significantly suppressed joint inflammation and cartilage proteoglycan depletion at day 4, as assessed by histology. Blocking IL-17 also clearly reduced bone erosions. Cathepsin K, a marker of osteoclast-like activity, and synovial RANKL mRNA expression were both suppressed. The degree of bone erosions strongly correlated with the severity of joint inflammation, suggesting that anti-IL-17 treatment reduced bone erosion by suppressing joint inflammation. Interestingly, blocking IL-17 suppressed synovial expression of both IL-1beta and tumor necrosis factor-alpha, whereas blocking IL-1 did not affect tumor necrosis factor-alpha levels. These data indicate that IL-17 is an important upstream mediator in joint pathology during flare-up of experimental arthritis.
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              Enthesitis: from pathophysiology to treatment

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                Author and article information

                Contributors
                eleni.kampylafka@uk-erlangen.de
                isabelle.oliveira@uk-erlangen.de
                christina.linz@uk-erlangen.de
                veronika.lerchen@uk-erlangen.de
                fabian.stemmler@uk-erlangen.de
                david.simon@uk-erlangen.de
                matthias.englbrecht@uk-erlangen.de
                michael.sticherling@uk-erlangen.de
                juergen.rech@uk-erlangen.de
                arnd.kleyer@uk-erlangen.de
                georg.schett@uk-erlangen.de
                +49 9131-85 43 036 , axel.hueber@uk-erlangen.de
                Journal
                Arthritis Res Ther
                Arthritis Res. Ther
                Arthritis Research & Therapy
                BioMed Central (London )
                1478-6354
                1478-6362
                27 July 2018
                27 July 2018
                2018
                : 20
                Affiliations
                [1 ]ISNI 0000 0001 2107 3311, GRID grid.5330.5, Department of Internal Medicine 3 – Rheumatology and Immunology, , Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, ; Ulmenweg 18, 91054 Erlangen, Germany
                [2 ]ISNI 0000 0001 2107 3311, GRID grid.5330.5, Department of Dermatology, , Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, ; Ulmenweg 18, 91054 Erlangen, Germany
                Article
                1653
                10.1186/s13075-018-1653-5
                6063019
                30053825
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Orthopedics

                psoriatic arthritis, bone, erosions, enthesiophytes, synovitis, bdmards

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