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Blockade of intra-articular TNF in peripheral spondyloarthritis: Its relevance to clinical scores,quantitative imaging and synovial fluid and synovial tissue biomarkers
Authors:Ugo Fiocco  Paolo Sfriso  Francesca Oliviero  Francesca Lunardi  Fiorella Calabrese  Elena Scagliori  Luisella Cozzi  Antonio Di Maggio  Roberto Nardacchione  Béatrice Molena  Mara Felicetti  Katia Gazzola  Roberto Stramare  Léopoldo Rubaltelli  Benedetta Accordi  Luisa Costa  Pascale Roux-Lombard  Leonardo Punzi  Jean-Michel Dayer
Institution:1. Department of Medicine, University of Padova, Via Giustiniani, 2, 35128 Padova, Italy;2. Department of Medical-Diagnostic Science and Special Therapies, University of Padova, Padova, Italy;3. Department of Orthopedics, Leonardo Foundation, Abano Terme General Hospital, Abano Terme (PD), Italy;4. Oncohematology Laboratory, Department of Pediatrics, University of Padova, Padova, Italy;5. Rheumatology Research Unit, Department of Clinical and Experimental Medicine, University Federico II, Naples, Italy;6. Immunology and Allergy Division, Geneva University Hospitals and University of Geneva, 4, rue Gabrielle Perret-Gentil, CH-1211 Geneva, Switzerland;7. Faculty of Medicine, CMU, 1, rue Michel-Servet, CH-1211 Geneva, Switzerland
Abstract:ObjectivesThis open-label study is based on a translational approach with the aim of detecting changes in the clinical condition as well as in imaging and synovial biological markers in both synovial fluid (SF) and synovial tissue (ST) in peripheral spondyloarthritis (SpA) patients following intra-articular (IA) blockade of TNF-α by serial etanercept injections.MethodsTwenty-seven SpA patients with resistant knee synovitis underwent four biweekly IA injections of etanercept (E) (12.5 mg). The primary outcome of Thompson's Knee Index (THOMP), and secondary outcomes of Knee Joint Articular Index (KJAI), C-reactive protein (CRP), HAQ-Disability Index (HAQ-DI), maximal synovial thickness (MST) according to ultrasonography (US) and contrast-enhanced magnetic resonance (C+MR) imaging, ST-CD45+ mononuclear cells (MNC) and ST-CD31+ vessels, IL-1β, IL-1Ra and IL-6 levels in SF were assessed at baseline and at the end of the study.ResultsAt the study end, clinical and imaging outcomes as well as ST and SF biological markers were significantly reduced compared to baseline. There were significant correlations between clinical, imaging and biological markers (CRP with either THOMP, or KJAI, or HAQ-DI or SF-IL-1Ra; US-MST with KJAI, ST-CD45+ with either THOMP, or KJAI, or ST-CD31+, or SF-IL-1β; SF-IL-6 with either THOMP, or KJAI, or SF-IL-1β, or IL-1Ra).ConclusionsThe proof of concept study revealed early improvement either in local and systemic clinical scores, in synovial thickness measures by C+MR and US, or expression of synovial biological markers. CD45+, CD31+ in ST and IL-6 and IL-1β in SF may be considered potential biomarkers of the peripheral SpA response to IA TNF-α blocking.
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