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Spinal Diseases: HELP
Articles by Douglas James Veale
Based on 33 articles published since 2009
(Why 33 articles?)
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Between 2009 and 2019, D. Veale wrote the following 33 articles about Spinal Diseases.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline Treating axial spondyloarthritis and peripheral spondyloarthritis, especially psoriatic arthritis, to target: 2017 update of recommendations by an international task force. 2018

Smolen, Josef S / Schöls, Monika / Braun, Jürgen / Dougados, Maxime / FitzGerald, Oliver / Gladman, Dafna D / Kavanaugh, Arthur / Landewé, Robert / Mease, Philip / Sieper, Joachim / Stamm, Tanja / Wit, Maarten de / Aletaha, Daniel / Baraliakos, Xenofon / Betteridge, Neil / Bosch, Filip van den / Coates, Laura C / Emery, Paul / Gensler, Lianne S / Gossec, Laure / Helliwell, Philip / Jongkees, Merryn / Kvien, Tore K / Inman, Robert D / McInnes, Iain B / Maccarone, Mara / Machado, Pedro M / Molto, Anna / Ogdie, Alexis / Poddubnyy, Denis / Ritchlin, Christopher / Rudwaleit, Martin / Tanew, Adrian / Thio, Bing / Veale, Douglas / Vlam, Kurt de / van der Heijde, Désirée. ·Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria. · 2nd Department of Medicine, Hietzing Hospital, Vienna, Austria. · Health Consult, Vienna, Austria. · Rheumazentrum Ruhrgebiet, Ruhr-University Bochum, Herne, Germany. · Department of Rheumatology, Paris Descartes University, Paris, France. · Department of Rheumatology, St Vincent's University Hospital, Dublin, Ireland. · Division of Rheumatology, University of Toronto, Toronto, Ontario, Canada. · Division of Rheumatology, University of California, San Diego, CA, USA. · Amsterdam Rheumatology & Immunology Center, Amsterdam, The Netherlands. · Division of Rheumatology Research, Swedish-Providence St. Joseph Health System, University of Washington, Seattle, WA, USA. · Department of Gastroenterology, Infectiology and Rheumatology, Campus Benjamin Franklin, Charité Universitätsmedizin Berlin, Berlin, Berlin, Germany. · Section for Outcomes Research, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria. · Department of Medical Humanities, VU University Medical Centre, Amsterdam, The Netherlands. · Neil Betteridge Associates, UK. · Ghent University Hospital, Ghent, Belgium. · Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK. · Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, UK. · Department of Medicine, University of California, San Francisco, CA, USA. · Department of Rheumatology, UPMC Univ Paris 06, GRC-UPMC 08 (EEMOIS); AP-HP, Pitié Salpêtrière Hospital, Paris, France. · Institute of Molecular Medicine, University of Leeds, Leeds, UK. · Seayn Medical, Voorschoten, The Netherlands. · Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · University Health Network and University of Toronto, Toronto, Ontario, Canada. · University of Glasgow, College of Medical Veterinary and Life Sciences, Glasgow, UK. · A.DI.PSO. (Associazione per la Difesa degli Psoriasici)-PE.Pso.POF (Pan European Psoriasis Patients' Organization Forum), Rome, Italy. · Centre for Rheumatology & MRC Centre for Neuromuscular Diseases, University College London, London, UK. · Division of Rheumatology, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Pennsylvania, PA, USA. · German Rheumatism Research Centrer, Berlin, Germany. · Allergy, Immunology and Rheumatology Division, University of Rochester Medical Center Rochester, New York, NY, USA. · Division of Internal Medicine and Rheumatology, Klinikum Bielefeld, Bielefeld, Germany. · Department of Dermatology, Medical University of Vienna, Vienna, Austria. · Department of Dermatology, Erasmus Medical Center, Erasmus University, Rotterdam, The Netherlands. · Department of Rheumatology, Klinikum Bielefeld, Bielefeld, Germany. · Division of Rheumatology, University Hospitals Leuven, Leuven, Belgium. · Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. ·Ann Rheum Dis · Pubmed #28684559.

ABSTRACT: Therapeutic targets have been defined for axial and peripheral spondyloarthritis (SpA) in 2012, but the evidence for these recommendations was only of indirect nature. These recommendations were re-evaluated in light of new insights. Based on the results of a systematic literature review and expert opinion, a task force of rheumatologists, dermatologists, patients and a health professional developed an update of the 2012 recommendations. These underwent intensive discussions, on site voting and subsequent anonymous electronic voting on levels of agreement with each item. A set of 5 overarching principles and 11 recommendations were developed and voted on. Some items were present in the previous recommendations, while others were significantly changed or newly formulated. The 2017 task force arrived at a single set of recommendations for axial and peripheral SpA, including psoriatic arthritis (PsA). The most exhaustive discussions related to whether PsA should be assessed using unidimensional composite scores for its different domains or multidimensional scores that comprise multiple domains. This question was not resolved and constitutes an important research agenda. There was broad agreement, now better supported by data than in 2012, that remission/inactive disease and, alternatively, low/minimal disease activity are the principal targets for the treatment of PsA. As instruments to assess the patients on the path to the target, the Ankylosing Spondylitis Disease Activity Score (ASDAS) for axial SpA and the Disease Activity index for PSoriatic Arthritis (DAPSA) and Minimal Disease Activity (MDA) for PsA were recommended, although not supported by all. Shared decision-making between the clinician and the patient was seen as pivotal to the process. The task force defined the treatment target for SpA as remission or low disease activity and developed a large research agenda to further advance the field.

2 Guideline European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update. 2016

Gossec, L / Smolen, J S / Ramiro, S / de Wit, M / Cutolo, M / Dougados, M / Emery, P / Landewé, R / Oliver, S / Aletaha, D / Betteridge, N / Braun, J / Burmester, G / Cañete, J D / Damjanov, N / FitzGerald, O / Haglund, E / Helliwell, P / Kvien, T K / Lories, R / Luger, T / Maccarone, M / Marzo-Ortega, H / McGonagle, D / McInnes, I B / Olivieri, I / Pavelka, K / Schett, G / Sieper, J / van den Bosch, F / Veale, D J / Wollenhaupt, J / Zink, A / van der Heijde, D. ·Sorbonne Universités, UPMC Univ Paris 06, Institut Pierre Louis d'Epidémiologie et de Santé Publique, GRC-UPMC 08 (EEMOIS), Paris, France Department of rheumatology, AP-HP, Pitié Salpêtrière Hospital, Paris, France. · Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria Second Department of Medicine, Hietzing Hospital, Vienna, Austria. · Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands. · EULAR, representing People with Arthritis/Rheumatism in Europe (PARE), London, UK. · Research Laboratory and Clinical Division of Rheumatology, Department of Internal Medicine, University of Genova, Viale Benedetto, Italy. · Medicine Faculty, Paris Descartes University, Paris, France Rheumatology B Department, APHP, Cochin Hospital, Paris, France. · Leeds NIHR Musculoskeletal Biomedical Research Unit, LTHT, Leeds, UK Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK. · Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology Center, Amsterdam, The Netherlands Atrium Medical Center, Heerlen, The Netherlands. · North Devon, UK. · Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria. · Rheumazentrum Ruhrgebiet, Herne and Ruhr-Universität Bochum, Herne, Germany. · Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Germany. · Arthritis Unit, Department of Rheumatology, Hospital Clínic and IDIBAPS, Barcelona, Spain. · Belgrade University School of Medicine, Belgrade, Serbia. · Department of Rheumatology, St. Vincent's University Hospital and Conway Institute, University College Dublin, Dublin, Ireland. · Section of Rheumatology, Department of Clinical Sciences, Lund University, Lund, Sweden Sweden and School of Business, Engineering and Science, Halmstad University, Halmstad, Sweden. · Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK. · Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Laboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, KU Leuven, Belgium Division of Rheumatology, University Hospitals Leuven, Leuven, Belgium. · Department of Dermatology, University Hospital Münster, Münster, Germany. · A.DI.PSO. (Associazione per la Difesa degli Psoriasici)-PE.Pso.POF (Pan European Psoriasis Patients' Organization Forum), Rome, Italy. · Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK. · Rheumatology Department of Lucania, San Carlo Hospital of Potenza and Madonna delle Grazie Hospital of Matera, Potenza, Italy. · Institute and Clinic of Rheumatology Charles University Prague, Czech Republic. · Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany. · Department of Rheumatology, Campus Benjamin Franklin, Charité, Berlin, Germany. · Ghent University Hospital, Ghent, Belgium. · Centre for Arthritis and Rheumatic Disease, Dublin Academic Medical Centre, St. Vincent's University Hospital, Dublin, Ireland. · Schoen Klinik Hamburg, Rheumatology and Clinical Immunology, Hamburg, Germany. · Department of Rheumatology and Clinical Immunology, German Rheumatism Research Centre Berlin, Charité-University Medicine Berlin, Germany. ·Ann Rheum Dis · Pubmed #26644232.

ABSTRACT: BACKGROUND: Since the publication of the European League Against Rheumatism recommendations for the pharmacological treatment of psoriatic arthritis (PsA) in 2012, new evidence and new therapeutic agents have emerged. The objective was to update these recommendations. METHODS: A systematic literature review was performed regarding pharmacological treatment in PsA. Subsequently, recommendations were formulated based on the evidence and the expert opinion of the 34 Task Force members. Levels of evidence and strengths of recommendations were allocated. RESULTS: The updated recommendations comprise 5 overarching principles and 10 recommendations, covering pharmacological therapies for PsA from non-steroidal anti-inflammatory drugs (NSAIDs), to conventional synthetic (csDMARD) and biological (bDMARD) disease-modifying antirheumatic drugs, whatever their mode of action, taking articular and extra-articular manifestations of PsA into account, but focusing on musculoskeletal involvement. The overarching principles address the need for shared decision-making and treatment objectives. The recommendations address csDMARDs as an initial therapy after failure of NSAIDs and local therapy for active disease, followed, if necessary, by a bDMARD or a targeted synthetic DMARD (tsDMARD). The first bDMARD would usually be a tumour necrosis factor (TNF) inhibitor. bDMARDs targeting interleukin (IL)12/23 (ustekinumab) or IL-17 pathways (secukinumab) may be used in patients for whom TNF inhibitors are inappropriate and a tsDMARD such as a phosphodiesterase 4-inhibitor (apremilast) if bDMARDs are inappropriate. If the first bDMARD strategy fails, any other bDMARD or tsDMARD may be used. CONCLUSIONS: These recommendations provide stakeholders with an updated consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes in PsA, based on a combination of evidence and expert opinion.

3 Editorial Is there a need for new agents with novel mechanisms of action in psoriatic arthritis? 2014

Orr, Carl / Veale, Douglas James. ·Dublin Academic Medical Centre, Centre for Arthritis and Rheumatic Diseases, St Vincent's University Hospital and The Conway Institute of Biomolecular and Biomedical Research, University College Dublin, , Dublin, Ireland. ·Ann Rheum Dis · Pubmed #24790066.

ABSTRACT: -- No abstract --

4 Editorial New therapies and new goals for psoriatic arthritis. 2011

Veale, Douglas James. · ·Arthritis Rheum · Pubmed #21128255.

ABSTRACT: -- No abstract --

5 Review The pathogenesis of psoriatic arthritis. 2018

Veale, Douglas J / Fearon, Ursula. ·Rheumatology EULAR Centre of Excellence, St Vincent's University Hospital and University College Dublin, Dublin, Ireland. Electronic address: douglas.veale@ucd.ie. · Rheumatology EULAR Centre of Excellence, St Vincent's University Hospital and University College Dublin, Dublin, Ireland; Department of Molecular Rheumatology, Trinity Biomedical Science Institute, Trinity College Dublin, Dublin, Ireland. ·Lancet · Pubmed #29893226.

ABSTRACT: Psoriatic arthritis is a chronic, immune-mediated, inflammatory arthropathy that presents with inflammation of the joints and entheses, including those of the axial skeleton, and is associated with increased mortality from cardiovascular disease. Diagnosis is primarily based on clinical phenotype because of the diversity of the associated features, which can include skin and nail disease, dactylitis, uveitis, and osteitis. Improved understanding of the pathogenesis of psoriatic arthritis has led to the development of effective biologics and small-molecular drugs targeting specific cytokines and signalling pathways, which can prevent disease progression and improve quality of life. However, at least 40% of patients with psoriatic arthritis have only a partial response or fail to respond to such treatments. Cytokine inhibitors, mainly those specific for tumour necrosis factor and, more recently, the interleukin 23-T-helper-17 cell pathway, have been highly successful in the treatment of disease manifestations in several different tissues, although targeting the interleukin 23-T-helper-17 cell pathway might be more effective in psoriasis than in arthritis. However, the precise mechanisms underlying the pathogenesis of psoriatic arthritis-which include genetics, environmental factors, and immune-mediated inflammation-are complex, and the relationship between disease of the joint and that of other domains is poorly understood. Improving our understanding of psoriatic arthritis pathogenesis could help to establish validated biomarkers for diagnosis, predict therapeutic response and remission, develop precision medicines, and predict which patients will respond to which therapy. We discuss advances in pathogenetic translational research that could inform these issues.

6 Review Biomarkers for rheumatoid and psoriatic arthritis. 2015

Verheul, M K / Fearon, U / Trouw, L A / Veale, D J. ·Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. · Centre for Arthritis and Rheumatic Diseases, Dublin Academic Medical Centre, UCD, Dublin, Ireland. · Centre for Arthritis and Rheumatic Diseases, Dublin Academic Medical Centre, UCD, Dublin, Ireland. Electronic address: douglas.veale@ucd.ie. ·Clin Immunol · Pubmed #25934385.

ABSTRACT: Rheumatic diseases, such as rheumatoid and psoriatic arthritis are systemic inflammatory conditions characterized by a chronic form of arthritis, often leading to irreversible joint damage. Early treatment for patients with rheumatic diseases is required to reduce or prevent joint injury. However, early diagnosis can be difficult and currently it is not possible to predict which individual patient will develop progressive erosive disease or who may benefit from a specific treatment according to their clinical features at presentation. Biomarkers are therefore required to enable earlier diagnosis and predict prognosis in both rheumatoid arthritis and psoriatic arthritis. In this review we will examine the evidence and current status of established and experimental biomarkers in rheumatoid and psoriatic arthritis for three important purposes; disease diagnosis, prognosis and prediction of response to therapy.

7 Review Psoriatic arthritis: recent progress in pathophysiology and drug development. 2013

Veale, Douglas James. · ·Arthritis Res Ther · Pubmed #24611179.

ABSTRACT: Psoriatic arthritis (PsA) is the second most common inflammatory arthropathy, after rheumatoid arthritis diagnosis, in early arthritis clinics. Most patients have established psoriasis, often for years, prior to the onset of joint pain and swelling; in addition, associated features of nail disease, dactylitis, enthesitis, spondylitis or uveitis may be present. Psoriasis may not be immediately apparent, as small or patchy lesions may occur in the scalp or perineum. PsA presents as a symmetrical polyarthritis, similar to rheumatoid arthritis, or an asymmetrical oligoarthritis with a predilection for the distal interphalangeal joints. Spinal involvement is similar, although not identical, to ankylosing spondylitis. Joint damage occurs early; up to 50% of PsA patients have an 11% annual erosion rate in the first 2 years of disease duration, suggesting it is not a benign condition. There have been significant advances in our understanding of PsA pathogenesis in recent years, in the areas of genetics and molecular biology, implicating both the innate and the adaptive immune systems. This has lead to the introduction of evidence-based targeted therapy, primarily with tumour necrosis factor inhibitor (TNFi) agents. Therapy with disease-modifying anti-rheumatic drugs, such as methotrexate and leflunomide, remains the first-choice therapeutic intervention, even though there are few randomised controlled trials with these agents. In contrast, a number of successful studies of TNFi agents demonstrate excellent efficacy, in combination with methotrexate, and several novel agents are currently in development for the treatment of PsA.

8 Review Enthesitis in psoriatic disease. 2012

McGonagle, Dennis G / Helliwell, Philip / Veale, Douglas. ·Department of Investigative Rheumatology, University of Leeds, Leeds, UK. D.G.McGonagle@leeds.ac.uk ·Dermatology · Pubmed #23108016.

ABSTRACT: Enthesitis is increasingly recognized as an important component in psoriatic arthritis (PsA). Improved imaging techniques have expanded our understanding of the role of enthesitis in PsA and provided methods for earlier detection and assessment. Increased knowledge about the extent of tendon and ligament involvement has led to the theory that enthesitis may be the primary event in PsA. Given the historical difficulties in detecting and measuring enthesitis, its inclusion as an endpoint in PsA trials has been limited. Current trial data suggest that tumour necrosis factor inhibitors can successfully treat PsA-related enthesitis, which may have implications for the long-term prognosis of PsA. In this article, we review methods for detecting and assessing enthesitis, current thinking regarding the role of enthesitis in the pathogenesis of PsA, and trial evidence for the treatment of PsA and, therefore, enthesitis.

9 Review How early should psoriatic arthritis be treated with a TNF-blocker? 2010

Harty, Leonard / Veale, Douglas James. ·Dublin Academic Medical Centre, Department of Rheumatology, St Vincent's University Hospital, University College Dublin, Dublin, Ireland. ·Curr Opin Rheumatol · Pubmed #20520552.

ABSTRACT: PURPOSE OF REVIEW: Psoriatic arthritis (PsA) is the second most commonly identified inflammatory arthropathy in early arthritis clinics. It is a complex multisystem disease involving the skin and joints, but may also present with inflammation of the spine - spondylitis, digits - dactylitis, eyes - uveitis and ligamentous insertions - enthesitis. The skin manifestations may be mild or patchy and often precede the joint inflammation. Joint erosions, however, may occur within the first 2 years in up to half of PsA patients and an erosion rate of 11% per annum has been reported suggesting it is not a benign disease as it was once regarded. RECENT FINDINGS: Therapy with mild anti-inflammatories is only beneficial in very mild or localized disease. In cases of more widespread joint involvement systemic therapy with disease-modifying antirheumatic drugs (DMARDs) such as methotrexate may be required and in the case of extra-articular or spinal disease, in which DMARDs have failed to show efficacy, biologic therapy may be highly effective. SUMMARY: The question of how early treatment should be instituted should be decided in a specialist rheumatology referral centre following appropriate assessment. Optimal therapy with combination DMARD and biologics may result in remission rates of up to 60%.

10 Review Cardiovascular disease and risk factors in patients with psoriasis and psoriatic arthritis. 2010

Tobin, Anne-Marie / Veale, Douglas J / Fitzgerald, Oliver / Rogers, Sarah / Collins, Paul / O'Shea, Donal / Kirby, Brian. ·Department of Dermatology, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland. tobin.annemarie@gmail.com ·J Rheumatol · Pubmed #20472927.

ABSTRACT: OBJECTIVE: Patients with psoriasis and psoriatic arthritis (PsA) have an increased incidence of cardiovascular disease (CVD) and cardiovascular risk factors such as smoking, hypertension, and metabolic syndrome compared to the normal population. Patients with psoriasis and PsA may also have increased risk from nonconventional risk factors such as raised levels of homocysteine and excessive alcohol consumption. We conducted a comprehensive review of the literature on CVD and all cardiovascular risk factors in patients with psoriasis and PsA. DATA SOURCES: All studies identified from a Medline (www.ncbi.nlm.nih.gov) search pertaining to CVD, individual risk factors in psoriasis, and PsA were included. STUDY SELECTION: Studies included a healthy reference population, were published between 1975 and 2009, and were written in English. RESULTS: Our search yielded 14 studies that documented rates of CVD in patients with psoriasis and PsA compared to controls. Substantial evidence points to elevated risk of CVD in patients with psoriasis and PsA. CONCLUSION: It remains difficult to conclude if risk factors are caused by psoriasis or share a common pathogenesis. Physicians treating patients with psoriasis and PsA must be aware of all potential cardiovascular risk factors in their patients.

11 Review Psoriatic arthritis management update - biotherapeutic options. 2009

Saber, Tajvur P / Veale, Douglas J. ·Centre for Arthritis Research and Education, Dublin Academic Health Care, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland. ·J Rheumatol Suppl · Pubmed #19661546.

ABSTRACT: Psoriatic arthritis (PsA) is a seronegative spondyloarthropathy (SpA) occurring in up to 30% of patients with psoriasis. It has a wide variation of annual incidence (median 6.4, range 0.1-3.1 per 10(5) people), based on analysis of 13 incidence and prevalence reviews published between 1987 and December 2006. Conventional treatments with antiinflammatory and disease modifying or antirheumatic drugs are not efficacious in all patients, in particular those with axial disease. This review examines new pharmacological developments in the treatment of PsA with a focus on biologic therapies.

12 Clinical Trial Change in CD3 positive T-cell expression in psoriatic arthritis synovium correlates with change in DAS28 and magnetic resonance imaging synovitis scores following initiation of biologic therapy--a single centre, open-label study. 2011

Pontifex, Eliza K / Gerlag, Danielle M / Gogarty, Martina / Vinkenoog, Marjolein / Gibbs, Adrian / Burgman, Ilse / Fearon, Ursula / Bresnihan, Barry / Tak, Paul Peter / Gibney, Robin G / Veale, Douglas J / FitzGerald, Oliver. ·Department of Rheumatology, St. Vincents University Hospital, Elm Park, Dublin 4, Ireland. elizapontifex@hotmail.com ·Arthritis Res Ther · Pubmed #21272347.

ABSTRACT: INTRODUCTION: With the development of increasing numbers of potential therapeutic agents in inflammatory disease comes the need for effective biomarkers to help screen for drug efficacy and optimal dosing regimens early in the clinical trial process. This need has been recognized by the Outcome Measures in Rheumatology Clinical Trials (OMERACT) group, which has established guidelines for biomarker validation. To seek a candidate synovial biomarker of treatment response in psoriatic arthritis (PsA), we determined whether changes in immunohistochemical markers of synovial inflammation correlate with changes in disease activity scores assessing 28 joints (ΔDAS28) or magnetic resonance imaging synovitis scores (ΔMRI) in patients with PsA treated with a biologic agent. METHODS: Twenty-five consecutive patients with PsA underwent arthroscopic synovial biopsies and MRI scans of an inflamed knee joint at baseline and 12 weeks after starting treatment with either anakinra (first 10 patients) or etanercept (subsequent 15 patients) in two sequential studies of identical design. DAS28 scores were measured at both time points. Immunohistochemical staining for CD3, CD68 and Factor VIII (FVIII) was performed on synovial samples and scored by digital image analysis (DIA). MRI scans performed at baseline and at 12 weeks were scored for synovitis semi-quantitatively. The ΔDAS28 of the European League Against Rheumatism good response definition (>1.2) was chosen to divide patients into responder and non-responder groups. Differences between groups (Mann Whitney U test) and correlations between ΔDAS28 with change in immunohistochemical and MRI synovitis scores (Spearman's rho test) were calculated. RESULTS: Paired synovial samples and MRI scans were available for 21 patients (8 anakinra, 13 etanercept) and 23 patients (8 anakinra, 15 etanercept) respectively. Change in CD3 (ΔCD3) and CD68 expression in the synovial sublining layer (ΔCD68sl) was significantly greater in the disease responders compared to non-responders following treatment (P = 0.005 and 0.013 respectively). ΔCD3, but not ΔCD68 or ΔFVIII, correlated with both ΔDAS28 (r = 0.49, P = 0.025) and ΔMRI (r = 0.58, P = 0.009). CONCLUSIONS: The correlation of ΔCD3 with ΔDAS28 and ΔMRI following biologic treatment in this cohort contributes to the validation of ΔCD3 as a synovial biomarker of disease response in PsA, and supports the further evaluation of ΔCD3 for predictive properties of future clinical outcomes.

13 Article Group for Research and Assessment of Psoriasis and Psoriatic Arthritis/Outcome Measures in Rheumatology Consensus-Based Recommendations and Research Agenda for Use of Composite Measures and Treatment Targets in Psoriatic Arthritis. 2018

Coates, Laura C / FitzGerald, Oliver / Merola, Joseph F / Smolen, Josef / van Mens, Leonieke J J / Bertheussen, Heidi / Boehncke, Wolf-Henning / Callis Duffin, Kristina / Campbell, Willemina / de Wit, Maarten / Gladman, Dafna / Gottlieb, Alice / James, Jana / Kavanaugh, Arthur / Kristensen, Lars Erik / Kvien, Tore K / Luger, Thomas / McHugh, Neil / Mease, Philip / Nash, Peter / Ogdie, Alexis / Rosen, Cheryl F / Strand, Vibeke / Tillett, William / Veale, Douglas J / Helliwell, Philip S. ·University of Leeds, Leeds, UK, and University of Oxford, Oxford, UK. · St. Vincent's University Hospital and University College Dublin, Dublin, Ireland. · Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. · Medical University of Vienna, Vienna, Austria. · Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands. · Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) , Oslo, Norway, and People with Arthritis/Rheumatism in Europe, Zurich, Switzerland. · Geneva University Hospital and Geneva University, Geneva, Switzerland. · University of Utah, Salt Lake City. · GRAPPA and Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada. · VU University Medical Centre and EMGO+ Research Institute, Amsterdam, The Netherlands. · University of Toronto and Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada. · New York Medical College, Valhalla, New York. · GRAPPA, Bath, UK. · University of California at San Diego. · Copenhagen University Hospital, Copenhagen, Denmark. · Diakonhjemmet Hospital, Oslo, Norway. · University Hospital Münster, Münster, Germany. · University of Bath, Bath, UK. · St. Joseph Health System, University of Washington, Seattle. · University of Queensland, Brisbane, Queensland, Australia. · University of Pennsylvania, Philadelphia. · Stanford University, Palo Alto, California. · Royal National Hospital for Rheumatic Diseases and University of Bath, Bath, UK. · University of Leeds, Leeds, UK. ·Arthritis Rheumatol · Pubmed #29193765.

ABSTRACT: OBJECTIVE: A meeting was convened by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and Outcome Measures in Rheumatology (OMERACT) to further the development of consensus among physicians and patients regarding composite disease activity measures and targets in psoriatic arthritis (PsA). METHODS: Prior to the meeting, physicians and patients completed surveys on outcome measures. A consensus meeting of 26 rheumatologists, dermatologists, and patient research partners reviewed evidence on composite measures and potential treatment targets plus results of the surveys. The meeting consisted of plenary presentations, breakout sessions, and group discussions. International experts including members of GRAPPA and OMERACT were invited to the meeting, including the developers of all of the measures discussed. After discussions, participants voted on proposals for use, and consensus was established in a second survey. RESULTS: Survey results from 128 health care professionals and 139 patients were analyzed alongside a systematic literature review summarizing evidence. A weighted vote was cast for composite measures. For randomized controlled trials, the most popular measures were the PsA disease activity score (40 votes) and the GRAPPA composite index (28 votes). For clinical practice, the most popular measures were an average of scores on 3 visual analog scales (45 votes) and the disease activity in PsA score (26 votes). After discussion, there was no consensus on a composite measure. The group agreed that several composite measures could be used and that future studies should allow further validation and comparison. The group unanimously agreed that remission should be the ideal target, with minimal disease activity (MDA)/low disease activity as a feasible alternative. The target should include assessment of musculoskeletal disease, skin disease, and health-related quality of life. The group recommended a treatment target of very low disease activity (VLDA) or MDA. CONCLUSION: Consensus was not reached on a continuous measure of disease activity. In the interim, the group recommended several composites. Consensus was reached on a treatment target of VLDA/MDA. An extensive research agenda was composed and recommends that data on all PsA clinical domains be collected in ongoing studies.

14 Article Determinants of Patient-Physician Discordance in Global Assessment in Psoriatic Arthritis: A Multicenter European Study. 2017

Desthieux, Carole / Granger, Benjamin / Balanescu, Andra Rodica / Balint, Peter / Braun, Jürgen / Canete, Juan D / Heiberg, Turid / Helliwell, Philip S / Kalyoncu, Umut / Kvien, Tore K / Kiltz, Uta / Niedermayer, Dora / Otsa, Kati / Scrivo, Rossana / Smolen, Josef / Stamm, Tanja A / Veale, Douglas J / de Vlam, Kurt / de Wit, Maarten / Gossec, Laure. ·Sorbonne Universités, UPMC University Paris 06, Institut Pierre Louis d'Epidémiologie et de Santé Publique, GRC-UPMC 08 (EEMOIS), AP-HP, Hôpital Pitié Salpêtrière, Paris, France. · University of Medicine and Pharmacy Carol Davila and St Maria Hospital, Bucharest, Romania. · National Institute of Rheumatology and Physiotherapy, Budapest, Hungary. · Ruhrgebiet, Herne and Ruhr-Universität Bochum, Herne, Germany. · Hospital Clínic and IDIBAPS, Barcelona, Spain. · Østfold University College, Halden, and Regional Research Support, Oslo University Hospital, Oslo, Norway. · University of Leeds, Leeds, UK. · Hacettepe University, Ankara, Turkey. · Diakonhjemmet Hospital, Oslo, Norway. · Tallinn Central Hospital, Tallinn, Estonia. · Sapienza Università di Roma, Rome, Italy. · III Medical University of Vienna, Vienna, Austria. · Dublin Academic Medical Centre and St Vincent's University Hospital, Dublin, Ireland. · University Hospitals Leuven, Leuven, Belgium. · Patient Research Partner, People with Arthritis/Rheumatism in Europe, Zurich, Switzerland. ·Arthritis Care Res (Hoboken) · Pubmed #27998026.

ABSTRACT: OBJECTIVE: Patient-physician discordance in global assessment of disease activity concerns one-third of patients, but what does it reflect? We aimed to assess patient-physician discordance in psoriatic arthritis (PsA) and patient-reported domains of health (physical and psychological) associated with discordance. METHODS: We analyzed the PsAID (Psoriatic Arthritis Impact of Disease), a cross-sectional, multicenter European study of patients with PsA according to expert opinion. Patient global assessment (PGA) and physician global assessment (PhGA) were rated on a 0-10 numeric rating scale. Discordance was defined as the difference (PGA-PhGA) and as the absolute difference |PGA-PhGA| ≥3 points. Determinants of PGA-PhGA were assessed by a stepwise multivariate linear regression among 12 physical and psychological aspects of impact: pain, skin problems, fatigue, ability to work/leisure, functional incapacity, feeling of discomfort, sleep disturbance, anxiety/fear, coping, embarrassment/shame, social participation, and depressive affects. RESULTS: In 460 patients (mean ± SD age 50.6 ± 12.9 years, 52.2% female, mean ± SD disease duration 9.5 ± 9.5 years, mean ± SD Disease Activity Index for Psoriatic Arthritis score 30.8 ± 32.4, and 40.4% undergoing treatment with biologic agents), the mean ± SD PGA was higher than the mean PhGA, with a mean absolute difference of 1.9 ± 1.8 points. Discordance defined by |PGA-PhGA| ≥3 of 10 concerned 134 patients (29.1%), and 115 patients (85.8% of the patients with discordance) had PGA>PhGA. Higher fatigue (β = 0.14), lower self-perceived coping (β = 0.23), and impaired social participation (β = 0.16) were independently associated with a higher difference (PGA-PhGA). CONCLUSION: Discordance concerned 29.1% of these patient/physician dyads, mainly by PGA>PhGA. Factors associated with discordance were psychological rather than physical domains of health. Discordance was more frequent in patients in remission, indicating more work is needed on the patient perspective regarding disease activity.

15 Article Fatigue in psoriatic arthritis - a cross-sectional study of 246 patients from 13 countries. 2016

Gudu, Tania / Etcheto, Adrien / de Wit, Maarten / Heiberg, Turid / Maccarone, Mara / Balanescu, Andra / Balint, Peter V / Niedermayer, Dora S / Cañete, Juan D / Helliwell, Philip / Kalyoncu, Umut / Kiltz, Uta / Otsa, Kati / Veale, Douglas J / de Vlam, Kurt / Scrivo, Rossana / Stamm, Tanja / Kvien, Tore K / Gossec, Laure. ·Department of Rheumatology, Sorbonne universités, UPMC université Paris 06, institut Pierre-Louis d'épidémiologie et de santé publique, GRC-UPMC 08 (EEMOIS), Pitié-Salpêtrière Hospital, AP-HP, 47-83, boulevard de l'Hôpital, 75013 Paris, France; Research Center of Rheumatic Diseases, University of Medicine and Pharmacy Carol Davila, St Maria Hospital, 011172 Bucharest, Romania. · Epidemiology and Biostatistics Unit, Sorbonne Paris Cité Research Center, Inserm U1153, 75014 Paris, France. · Patient Research Partner, People with Arthritis/Rheumatism in Europe (PARE), 8802 Zurich, Switzerland. · Department of Health and Social Sciences, Østfold University College, Halden, Regional Research Support, Oslo University Hospital, 4950 Oslo, Norway. · Patient Research Partner, ADIPSO (Associazione per la Difesa degli Psoriasici)-PE.Pso.POF (Pan European Psoriasis Patients' Organization Forum), 00193 Rome, Italy. · Research Center of Rheumatic Diseases, University of Medicine and Pharmacy Carol Davila, St Maria Hospital, 011172 Bucharest, Romania. · 3rd Rheumatology Department, National Institute of Rheumatology and Physiotherapy, 1023 Budapest, Hungary. · Arthritis Unit, Department of Rheumatology, Hospital Clínic and IDIBAPS, 08036 Barcelona, Spain. · Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, LS7 4SA Leeds, UK. · Division of Rheumatology, Faculty of Medicine, Hacettepe University, 06100 Ankara, Turkey. · Rheumazentrum Ruhrgebiet, Herne and Ruhr-Universität Bochum, 44652 Herne, Germany. · Rheumatology Department, Tallinn Central Hospital, 10138 Tallinn, Estonia. · Dublin Academic Medical Centre, St Vincent's University Hospital, D4 Dublin, Ireland. · Department of Rheumatology, University Hospitals Leuven, 3000 Leuven, Belgium. · Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, 00185 Rome, Italy. · Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, 1090 Vienna, Austria. · Department of Rheumatology, Diakonhjemmet Hospital, No-0370 Oslo, Norway. · Department of Rheumatology, Sorbonne universités, UPMC université Paris 06, institut Pierre-Louis d'épidémiologie et de santé publique, GRC-UPMC 08 (EEMOIS), Pitié-Salpêtrière Hospital, AP-HP, 47-83, boulevard de l'Hôpital, 75013 Paris, France. Electronic address: laure.gossec@aphp.fr. ·Joint Bone Spine · Pubmed #27055727.

ABSTRACT: OBJECTIVES: Fatigue is an aspect of psoriatic arthritis (PsA), which is important to patients. The objective was to evaluate magnitude of fatigue in PsA patients and to assess factors that might explain high levels of fatigue. METHODS: This was an ancillary analysis of a cross-sectional study in 13 countries of unselected PsA patients who fulfilled the CASPAR criteria. Patient-perceived importance of fatigue was assessed through a priority exercise. Levels of fatigue were assessed by a numeric rating scale (range 0-10). Factors potentially associated with fatigue>5/10: i.e., demographic variables (age, gender, disease duration, education level) and disease related characteristics including joint counts, C-reactive protein, skin psoriasis, axial involvement, enthesitis, dactylitis, structural damage, were assessed by univariate, multivariate logistic and multiple linear regression. RESULTS: In all, 246 patients were analysed: mean±standard deviation age 51.2±13.0years, mean disease duration 9.9±10.1years, mean DAS28 3.5±1.3. Fatigue was ranked second in patient-perceived importance, after pain. Magnitude of fatigue was high: mean fatigue 5.0±3.0. Fatigue>5/10 was well explained (variance explained 73%) by skin psoriasis (odds ratio 4.67 [95% confidence interval 1.05; 20.72]), tender joints (1.30 [1.01; 1.68]) and lower education level (1.09 [1.02; 1.23]). In the multiple linear regression model, fatigue was explained by skin psoriasis, tender joints, enthesitis, female gender, education level. CONCLUSIONS: Fatigue is a priority for PsA patients. Fatigue levels were high in these patients and fatigue>5/10 was mainly associated with disease-related factors but also patient-related variables, indicating that the etiology of fatigue in PsA is multifactorial.

16 Article Patient global assessment in psoriatic arthritis - what does it mean? An analysis of 223 patients from the Psoriatic arthritis impact of disease (PsAID) study. 2016

Tälli, Sandra / Etcheto, Adrien / Fautrel, Bruno / Balanescu, Andra / Braun, Jurgen / Cañete, Juan D / de Vlam, Kurt / de Wit, Maarten / Heiberg, Turid / Helliwell, Philip / Kalyoncu, Umut / Kiltz, Uta / Maccarone, Mara / Niedermayer, Dora / Otsa, Kati / Scrivo, Rossana / Smolen, Josef S / Stamm, Tanja / Veale, Douglas J / Kvien, Tore K / Gossec, Laure. ·Sorbonne universités, UPMC université Paris 06, institut Pierre-Louis d'épidémiologie et de santé publique, 75013 Paris, France; AP-HP, Pitié-Salpêtrière hospital, department of rheumatology, 47-83, boulevard de l'Hôpital, 75013 Paris, France. · Paris Descartes university, department of rheumatology, Cochin hospital and epidemiology, 75014 Paris, France; Biostatistics unit, Sorbonne Paris Cité research center, Inserm U1153, 75004 Paris, France. · Research center of rheumatic diseases, Sf. Maria hospital, university of medicine and pharmacy Carol Davila, 011172 Bucharest, Romania. · Rheumazentrum Ruhrgebiet, 44649 Herne, Germany; Ruhr-Universität Bochum, 44801 Bochum, Germany. · Arthritis unit, department of rheumatology, hospital Clínic and IDIBAPS, 08036 Barcelona, Spain. · Department of rheumatology, university hospitals Leuven, 1348 Leuven, Belgium. · People with Arthritis/Rheumatism in Europe (PARE), 8000 Zurich, Switzerland. · Faculty of health and social studies, Oestfold university college, NO-1757 Halden, regional research support Oslo, university hospital Postbox 4956 Nydalen, NO-0424 Oslo, Norway. · Institute of rheumatic and musculoskeletal medicine, university of Leeds, LS2 9JT Leeds, United Kindom. · University faculty of medicine, division of rheumatology, 06560 Ankara, Turkey. · Associazione per la Difesa degli Psoriasici (ADIPSO) - Pan European Psoriasis Patients' Organization Forum (PE.Pso.POF), 00193 Rome, Italy. · 3rd rheumatology department, National institute of rheumatology and physiotherapy, 1051 Budapest, Hungary. · East-Tallinn central hospital, rheumatology department, 10001 Tallinn, Estonia. · Dipartimento di medicina interna e specialità mediche, reumatologia, Sapienza università di Roma, 00185 Rome, Italy. · Division of rheumatology, department of medicine 3, medical university of Vienna, 2nd department of medicine, Hietzing hospital, 1130 Vienna, Austria. · Division of rheumatology, department of medicine 3, medical university of Vienna, 2nd department of medicine, Hietzing hospital, 1130 Vienna, Austria; University of applied sciences FH Campus Wien, department of health, division of health assisting engineering, 1140 Vienna, Austria. · Dublin academic medical centre, Saint-Vincent's university hospital, Elm Park, Dublin 4, Ireland. · Department of rheumatology, Diakonhjemmet hospital, 0370 Oslo, Norway. · Sorbonne universités, UPMC université Paris 06, institut Pierre-Louis d'épidémiologie et de santé publique, 75013 Paris, France; AP-HP, Pitié-Salpêtrière hospital, department of rheumatology, 47-83, boulevard de l'Hôpital, 75013 Paris, France. Electronic address: laure.gossec@psl.aphp.fr. ·Joint Bone Spine · Pubmed #26677994.

ABSTRACT: OBJECTIVE: Patient global assessment is a key outcome measure in psoriatic arthritis. To explore the meaning of patient global assessment in psoriatic arthritis by examining associations to domains of health assessed by the Psoriatic arthritis impact of disease score. METHODS: Post-hoc analysis of a multicentre cross-sectional study of patients with psoriatic arthritis. Data collection included patient global assessment, specific joint and skin global patient assessments, Psoriatic arthritis impact of disease questions covering physical (including joints and skin), psychological and social impact, and other comparator outcomes. Univariate analyses (Pearson correlation) and multivariate linear regression were performed to explain patient global assessment and the specific joint and skin global patient assessments. RESULTS: Among 223 patients (mean age: 51.0 [standard deviation, ±13.3] years; mean disease duration: 9.9 [±10.1] years; mean swollen joint count: 4.1 [±5.1]; 84.3% with current psoriasis [mainly of less than 5% body surface area]), 50.2% were females. Mean patient global assessment was 4.8 (±2.7), mean joint and skin patient assessments were respectively 5.6 (±2.5) and 4.1 (±3.0). Intraclass correlation between patient global assessment and joint or skin patient assessment was respectively 0.71 (95% confidence interval, 0.64-0.77) and 0.52 (95% confidence interval, 0.42-0.60). In multivariate analyses, patient global assessment was explained (R(2) of model: 0.754) by coping (β = 0.287); pain (β = 0.240); work and/or leisure activities (β = 0.141); and anxiety (β = 0.109). CONCLUSIONS: Patient global assessment in psoriatic arthritis was explained mainly by physical, but also psychological aspects of the disease.

17 Article Tofacitinib regulates synovial inflammation in psoriatic arthritis, inhibiting STAT activation and induction of negative feedback inhibitors. 2016

Gao, W / McGarry, T / Orr, C / McCormick, J / Veale, D J / Fearon, U. ·Centre for Arthritis and Rheumatic Diseases, Dublin Academic Medical Centre, St Vincent's University Hospital, Dublin, Ireland. ·Ann Rheum Dis · Pubmed #26353790.

ABSTRACT: BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory disease, characterised by synovitis and destruction of articular cartilage/bone. Janus-kinase and signal transducer and activator of transcription (JAK-STAT) signalling pathway is implicated in the pathogenesis of PsA. OBJECTIVES: To examine the effect of tofacitinib (JAK inhibitor) on proinflammatory mechanisms in PsA. METHODS: Primary PsA synovial fibroblasts (PsAFLS) and ex vivo PsA synovial explants were cultured with tofacitinib (1 µM). PhosphoSTAT3 (pSTAT3), phosphoSTAT1 (pSTAT1), suppressor of cytokine signaling-3 (SOCS3), protein inhibitor of activated Stat3 (PIAS3) and nuclear factor kappa B cells (NFκBp65) were quantified by western blot. The effect of tofacitinib on PsAFLS migration, invasion, Matrigel network formation and matrix metallopeptidase (MMP)2/9 was quantified by invasion/migration assays and zymography. Interleukin (IL)-6, IL-8, IFN-gamma-inducible protein 10 (IP-10) monocyte chemoattractant protein (MCP)-1, IL-17, IL-10, MMP3 and tissue inhibitor of metalloproteinases 3 (TIMP3) were assessed by ELISA. RESULTS: Tofacitinib significantly decreased pSTAT3, pSTAT1, NFκBp65 and induced SOCS3 and PIAS3 expression in PsAFLS and synovial explant cultures (p<0.05). Functionally, PsAFLS invasion, network formation and migration were inhibited by tofacitinib (all p<0.05). In PsA explant, tofacitinib significantly decreased spontaneous secretion of IL-6, IL-8, MCP-1, MMP9/MMP2, MMP3 (all p<0.05) and decreased the MMP3/TIMP3 ratio (p<0.05), with no effect observed for IP-10 or IL-10. CONCLUSIONS: This study further supports JAK-STAT inhibition as a therapeutic target for the treatment of PsA.

18 Article A clinically based protein discovery strategy to identify potential biomarkers of response to anti-TNF-α treatment of psoriatic arthritis. 2016

Collins, Emily S / Butt, Aisha Q / Gibson, David S / Dunn, Michael J / Fearon, Ursula / van Kuijk, Arno W / Gerlag, Danielle M / Pontifex, Eliza / Veale, Douglas J / Tak, Paul P / FitzGerald, Oliver / Pennington, Stephen R. ·School of Medicine and Medical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin, Ireland. · Department of Rheumatology, St Vincent's University Hospital, Elm Park, Dublin, Ireland. · Northern Ireland Centre for Stratified Medicine, University of Ulster, C-TRIC, Londonderry, UK. · Department of Clinical Immunology and Rheumatology, F4-105, Academic Medical Centre/University of Amsterdam, Amsterdam, The Netherlands. ·Proteomics Clin Appl · Pubmed #26108918.

ABSTRACT: PURPOSE: Psoriatic arthritis (PsA) can be treated using biologic therapies targeting biomolecules such as tumor necrosis factor alpha, interleukins (IL)-17 and IL-23. Although 70% PsA patients respond well to therapy, 30% patients show no or limited clinical improvement. Biomarkers that predict response to therapy would help to avoid unnecessary use of expensive biologics in nonresponding patients and enable alternative treatments to be explored. EXPERIMENTAL DESIGN: Patient synovial tissue samples from two clinical studies were analysed using difference in-gel electrophoresis-based proteomics to identify protein expression differences in response to anti-TNF-α treatment. Subsequent multiplexed MRM measurements were used to verify potential biomarkers. RESULTS: A total of 119 proteins were differentially expressed (p<0.05) in response to anti-TNF-α treatment and 25 proteins were differentially expressed (p<0.05) between "good responders" and "poor responders". From these differentially expressed proteins, MRM assays were developed for four proteins to explore their potential as treatment predictive biomarkers. CONCLUSION AND CLINICAL RELEVANCE: Gel-based proteomics strategy has demonstrated differential protein expression in synovial tissue of PsA patients, in response to anti-TNF-α treatment. Development of multiplex MRM assays to these differentially expressed proteins has the potential to predict response to therapy and allow alternative, more effective treatments to be explored sooner.

19 Article Redox-mediated angiogenesis in the hypoxic joint of inflammatory arthritis. 2014

Biniecka, Monika / Connolly, Mary / Gao, Wei / Ng, Chin T / Balogh, Emese / Gogarty, Martina / Santos, Lelani / Murphy, Evelyn / Brayden, David / Veale, Douglas J / Fearon, Ursula. ·Dublin Academic Medical Centre and St. Vincent's University Hospital, Dublin, Ireland. ·Arthritis Rheumatol · Pubmed #25155522.

ABSTRACT: OBJECTIVE: Inflammatory arthritis is associated with joint inflammation, synovial tissue proliferation, and degradation of articular cartilage and bone. Angiogenesis is an early and fundamental component of synovial inflammation. Oxygen metabolism is recognized as an important mediator of joint vascular remodeling. The aim of this study was to determine whether in vivo synovial hypoxia (tissue PO2 [tPO2 ]) and tumor necrosis factor (TNF) blocking therapy alter synovial vascular expression of NADPH oxidase (NOX) and how this action regulates angiogenic mechanisms. METHODS: NOX-2 protein and messenger RNA expression was examined in patients with inflammatory arthritis before and after receiving TNF inhibitor (TNFi) therapy and in mice with collagen-induced arthritis (CIA). Proangiogenic processes were assessed in human microvascular endothelial cells (HMVECs) following culture with NOX-2 activators (TNFα and 4-hydroxynonenal), small interfering RNA (siRNA) for NOX, and the inhibitor diphenyleneiodonium (DPI) under conditions of normoxia or 3% hypoxia. RESULTS: We demonstrated significantly increased NOX-2 expression in the joints of patients with inflammatory arthritis and the joints of mice with CIA as compared to controls. NOX-2 expression was higher in patients with synovial tPO2 levels <3% than in those with tPO2 levels >3% (P < 0.05), and correlated with in vivo macroscopic/microscopic measures of angiogenesis, such as vascularity and levels of vascular endothelial growth factor, angiopoietin 2, factor VIII, neural cell adhesion molecule, and α-smooth muscle actin (P < 0.05 for all). A decrease in NOX-2 expression was paralleled by an increase in in vivo tPO2 levels only in those patients who were defined as TNFi responders. In vitro NOX-2 activators and 3% hypoxia significantly promoted HMVEC migration, angiogenic tube formation, and secretion of proangiogenic mediators, effects that were blocked by siRNA for NOX-2 or the NOX-2 inhibitor DPI. CONCLUSION: We demonstrated that hypoxia activates NOX-2 protein expression, and NOX-2-induced oxidative stress may be an initiating factor in driving angiogenesis.

20 Article A patient-derived and patient-reported outcome measure for assessing psoriatic arthritis: elaboration and preliminary validation of the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire, a 13-country EULAR initiative. 2014

Gossec, Laure / de Wit, Maarten / Kiltz, Uta / Braun, Juergen / Kalyoncu, Umut / Scrivo, Rossana / Maccarone, Mara / Carton, Laurence / Otsa, Kati / Sooäär, Imre / Heiberg, Turid / Bertheussen, Heidi / Cañete, Juan D / Sánchez Lombarte, Anselm / Balanescu, Andra / Dinte, Alina / de Vlam, Kurt / Smolen, Josef S / Stamm, Tanja / Niedermayer, Dora / Békés, Gabor / Veale, Douglas / Helliwell, Philip / Parkinson, Andrew / Luger, Thomas / Kvien, Tore K / Anonymous690793. ·Department of Rheumatology, UPMC University Paris 06, GRC-UPMC 08 (EEMOIS) and AP-HP, Pitié Salpêtrière Hospital, , Paris, France. ·Ann Rheum Dis · Pubmed #24790067.

ABSTRACT: INTRODUCTION: The objective was to develop a questionnaire that can be used to calculate a score reflecting the impact of psoriatic arthritis (PsA) from the patients' perspective: the PsA Impact of Disease (PsAID) questionnaire. METHODS: Twelve patient research partners identified important domains (areas of health); 139 patients prioritised them according to importance. Numeric rating scale (NRS) questions were developed, one for each domain. To combine the domains into a single score, relative weights were determined based on the relative importance given by 474 patients with PsA. An international cross-sectional and longitudinal validation study was performed in 13 countries to examine correlations of the PsAID score with other PsA or generic disease measures. Test-retest reliability and responsiveness (3 months after a treatment change) were examined in two subsets of patients. RESULTS: Two PsAID questionnaires were developed with both physical and psychological domains: one for clinical practice (12 domains of health) and one for clinical trials (nine domains). Pain, fatigue and skin problems had the highest relative importance. The PsAID scores correlated well with patient global assessment (N=474, Spearman r=0.82-0.84), reliability was high in stable patients (N=88, intraclass correlation coefficient=0.94-0.95), and sensitivity to change was also acceptable (N=71, standardised response mean=0.90-0.91). CONCLUSIONS: A questionnaire to assess the impact of PsA on patients' lives has been developed and validated. Two versions of the questionnaire are available, one for clinical practice (PsAID-12) and one for clinical trials (PsAID-9). The PsAID questionnaires should allow better assessment of the patient's perspective in PsA. Further validation is needed.

21 Article Glycosylation status of serum in inflammatory arthritis in response to anti-TNF treatment. 2013

Collins, Emily S / Galligan, Marie C / Saldova, Radka / Adamczyk, Barbara / Abrahams, Jodie L / Campbell, Matthew P / Ng, Chin-Teck / Veale, Douglas J / Murphy, Thomas B / Rudd, Pauline M / Fitzgerald, Oliver. ·Department of Rheumatology, Dublin Academic Medical Centre, Dublin 4, Ireland. ·Rheumatology (Oxford) · Pubmed #23681398.

ABSTRACT: OBJECTIVE: Glycosylation is the most common post-translational modification and is altered in disease. The typical glycosylation change in patients with inflammatory arthritis (IA) is a decrease in galactosylation levels on IgG. The aim of this study is to evaluate the effect of anti-TNF therapy on whole serum glycosylation from IA patients and determine whether these alterations in the glycome change upon treatment of the disease. METHODS: Serum samples were collected from 54 IA patients before treatment and at 1 and 12 months after commencing anti-TNF therapy. N-linked glycans from whole serum samples were analysed using a high-throughput hydrophilic interaction liquid chromatography-based method. RESULTS: Glycosylation on the serum proteins of IA patients changed significantly with anti-TNF treatment. We observed an increase in galactosylated glycans from IgG, also an increase in core-fucosylated biantennary galactosylated glycans and a decrease in sialylated triantennary glycans with and without outer arm fucose. This increase in galactosylated IgG glycans suggests a reversing of the N-glycome towards normal healthy profiles. These changes are strongly correlated with decreasing CRP, suggesting a link between glycosylation changes and decreases in inflammatory processes. CONCLUSION: Glycosylation changes in the serum of IA patients on anti-TNF therapy are strongly associated with a decrease in inflammatory processes and reflect the effect of anti-TNF on the immune system.

22 Article Periarticular bone gain at proximal interphalangeal joints and changes in bone turnover markers in response to tumor necrosis factor inhibitors in rheumatoid and psoriatic arthritis. 2013

Szentpetery, Agnes / McKenna, Malachi J / Murray, Barbara F / Ng, Chin Teck / Brady, Jennifer J / Morrin, Michelle / Radovits, Bea / Veale, Douglas J / Fitzgerald, Oliver. ·Department of Rheumatology, the Metabolism Laboratory, St. Vincent's University Hospital, Dublin, Ireland. ·J Rheumatol · Pubmed #23457381.

ABSTRACT: OBJECTIVE: Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are characterized by periarticular bone erosion; periarticular bone formation is a feature in PsA. The effect of anti-tumor necrosis factor-α (TNF-α) on periarticular bone remodeling is unclear in both diseases. Our aim was to assess the response of bone turnover markers (BTM) and hand bone mineral density (BMD) to anti-TNF over 3 years in RA and PsA. METHODS: We measured serum bone-specific alkaline phosphatase (bone ALP), procollagen type-I N-propeptide (PINP), intact osteocalcin, C-terminal cross-linking telopeptides (CTX-I), urinary N-terminal cross-linking telopeptide of type-I collagen (NTX-I), and free deoxypyridinoline crosslinks (fDPD) at baseline, 1, 12, and 36 months. BMD measurements (hands/spine/hip) were obtained at 3 timepoints. RESULTS: We recruited 62 patients (RA 35; PsA 27). BTM correlated significantly with hand BMD but not with central BMD. Low hand BMD was associated with RA and increased BTM. Following anti-TNF therapy, hip BMD declined while spine and hand BMD were unchanged. Periarticular BMD at proximal interphalangeal (PIP) joints increased while it decreased at metacarpophalangeal joints. Bone ALP increased steadily and was always higher in PsA. PINP and intact osteocalcin increased to a lesser extent, but resorption markers did not change. CONCLUSION: At baseline, hand BMD was inversely associated with BTM. Bone formation rather than resorption markers better showed the bone response to anti-TNF. Despite a lack of effect on central BMD, the modest effect of anti-TNF on PIP BMD may provide evidence that BTM reflect specifically bone remodeling activity at periarticular sites of inflammation in RA and PsA.

23 Article Notch signalling pathways mediate synovial angiogenesis in response to vascular endothelial growth factor and angiopoietin 2. 2013

Gao, Wei / Sweeney, Catherine / Walsh, Ceara / Rooney, Peadar / McCormick, Jennifer / Veale, Douglas J / Fearon, Ursula. ·Department of Rheumatology, Translational Research Group, Dublin Academic Medical Centre, St Vincent's University Hospital, Dublin, Ireland. ·Ann Rheum Dis · Pubmed #23161900.

ABSTRACT: OBJECTIVE: Notch signalling pathways are critical for angiogenesis and endothelial cell (EC) fate; however the mechanisms regulating these processes in the inflamed joint remain to be elucidated. Here, we examine whether Notch signalling mediates vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang2)-induced vascular function. METHODS: Notch-1 intracellular domain (Notch-1 IC), Notch-4 IC, Delta-like-ligand 4, Hes-related transcriptional repressors-1 and 2 (Hrt-1, Hrt-2) mRNA and/or protein expression was measured by Real-time PCR and/or western blot. VEGF/Ang2 induced EC function was assessed using transwell invasion chambers, matrigel tube formation assays and wound repair scratch assays±Notch-1 siRNA or an γ-secretase inhibitor N-(N-(3,5-Difluorophenacetyl-L-alanly))-S-phenylglycine-t-Butyl Ester (DAPT) in RA synovial explants or human microvascular EC. Interleukin (IL)-6 and IL-8 were measured by ELISA and MMP2 and 9 by gelatine zymography. RESULTS: Notch-1 IC and Notch-4 IC protein expressions were demonstrated in RA and psoriatic arthritis synovial biopsies, with minimal expression observed in Osteoarthritis (OA). VEGF and Ang2 induced Notch-1 IC/ Notch-4 IC protein expression in synovial explant cultures and human microvascular EC levels were further potentiated by VEGF/Ang2 stimulation in combination. Notch-1, Delta-like-ligand 4, and Hrt-2 mRNA expression were significantly induced by VEGF and Ang2 alone and in combination. Furthermore VEGF/Ang2-induced EC invasion, angiogenesis and migration were inhibited by Notch-1 siRNA or DAPT. Conditioned media from VEGF/Ang2 stimulated RA synovial explants induced EC tube formation, an effect that was inhibited by DAPT. Finally, DAPT significantly decreased VEGF/Ang2 induced IL-6, IL-8, MMP2 and 9 expressions in RA synovial explants. CONCLUSIONS: Notch-1 mediates VEGF/Ang2-induced angiogenesis and EC invasion in inflammatory arthritis.

24 Article Joint tenderness and swelling in biologic-treated inflammatory arthritis patients - a tricky trade off? 2012

Harty, L C / Ng, C T / Fearon, C / Murray, C A / Fitzgerald, O / Veale, D J. ·Bone and Joint Unit, Department of Rheumatology, St Vincent's University Hospital, Dublin, Ireland. lenharty@yahoo.com ·Int J Clin Pract · Pubmed #22257038.

ABSTRACT: OBJECTIVE: To compare the pattern of joint responses in patients with rheumatoid arthritis and psoriatic arthritis treated with TNF inhibitor (TNFi) therapy. METHODS: A total of 182 PsA/Rheumatoid arthritis (RA) patients attending the rheumatology unit of a tertiary referral centre in Ireland were recruited and prospectively followed up by the attendant rheumatologists. Clinical progress of the patients was noted at baseline and 6 months after starting TNFi therapy. RESULTS: A total of 114 RA and 68 PsA patients were assessed; 20% of the patients had one of either tender joints or swollen joints after 6 months of therapy. Rheumatoid arthritis patients had a significantly higher proportion of non-tender swollen joints compared with PsA patients, whereas PsA patients had a higher proportion of tender non-swollen joints (p < 0.05). CONCLUSION: Residual joint swelling was found more commonly in RA patients than in PsA patients following TNFi therapy, whereas residual tender joints occurred more frequently in PsA; this may reflect enthesiopathy or periostitis.

25 Article Mitochondrial mutagenesis correlates with the local inflammatory environment in arthritis. 2012

Harty, Leonard C / Biniecka, Monika / O'Sullivan, Jacintha / Fox, Edward / Mulhall, Kevin / Veale, Douglas J / Fearon, Ursula. ·Translation Rheumatology Research Group, Dublin Academic Medical Centre, St Vincent’s University Hospital, Elm Park, Ireland. ·Ann Rheum Dis · Pubmed #22121133.

ABSTRACT: BACKGROUND: To examine the association between mitochondrial mutagenesis and the proinflammatory microenvironment in patients with inflammatory arthritis. METHODS: Fifty patients with inflammatory arthritis underwent arthroscopy and synovial tissue biopsies, synovial fluid and clinical assessment were obtained. Fifteen patients pre/post-TNFi therapy were also recruited. Normal synovial biopsies were obtained from 10 subjects undergoing interventional arthroscopy. Macroscopic synovitis/vascularity was measured by visual analogue scale. Cell-specific markers CD3 (T cells) and CD68 (macrophages) were quantified by immunohistology. TNFα, IL-6, IFNγ and IL-1β were measured in synovial fluids by MSD multiplex assays. Synovial tissue mitochondrial mutagenesis was quantified using a mitochondrial random mutation capture assay (RMCA). The direct effect of TNFα on oxidative stress and mitochondrial function was assessed in primary cultures of rheumatoid arthritis synovial fibroblast cells (RASFCs). Mitochondrial mutagenesis, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and mitochondrial mass (MM) were quantified using the RMCA and specific cell fluorescent probes. RESULTS: A significant increase in mtDNA mutation frequency was demonstrated in inflamed synovial tissue compared with control (p<0.05), an effect that was independent of age. mtDNA mutations positively correlated with macroscopic synovitis (r=0.52, p<0.016), vascularity (r=0.54, p<0.01) and with synovial fluid cytokine levels of TNFα (r=0.74, p<0.024) and IFNγ (r=0.72, p<0.039). mtDNA mutation frequency post-TNFi therapy was significantly lower in patients with a DAS<3.2 (p<0.05) and associated with clinical and microscopic measures of disease (p<0.05). In vitro TNFα significantly induced mtDNA mutations, ROS, MM and MMP in RASFCs (all p<0.05). CONCLUSION: High mitochondrial mutations are strongly associated with synovial inflammation showing a direct link between mitochondrial mutations and key proinflammatory pathways.

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