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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 references33

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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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            Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction

            In autoimmune arthritis, traditionally classified as a T helper (Th) type 1 disease, the activation of T cells results in bone destruction mediated by osteoclasts, but how T cells enhance osteoclastogenesis despite the anti-osteoclastogenic effect of interferon (IFN)-γ remains to be elucidated. Here, we examine the effect of various Th cell subsets on osteoclastogenesis and identify Th17, a specialized inflammatory subset, as an osteoclastogenic Th cell subset that links T cell activation and bone resorption. The interleukin (IL)-23–IL-17 axis, rather than the IL-12–IFN-γ axis, is critical not only for the onset phase, but also for the bone destruction phase of autoimmune arthritis. Thus, Th17 is a powerful therapeutic target for the bone destruction associated with T cell activation.
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              Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial.

              Interleukin 17A is a proinflammatory cytokine that is implicated in the pathogenesis of psoriatic arthritis. We assessed the efficacy and safety of subcutaneous secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis.
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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
                : 153
                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
                Author information
                http://orcid.org/0000-0001-6454-1234
                Article
                1653
                10.1186/s13075-018-1653-5
                6063019
                30053825
                1d3298b8-9721-45d6-b16f-4aa7af8ebc23
                © 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.

                History
                : 9 April 2018
                : 27 June 2018
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

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

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