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Psoriasis: HELP
Articles from University of Ghent
Based on 58 articles published since 2008
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These are the 58 published articles about Psoriasis that originated from University of Ghent during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
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 MAIT cells: not just another brick in the wall. 2016

Debusschere, Karlijn / Lories, Rik J / Elewaut, Dirk. ·Department of Internal Medicine-Rheumatology, Ghent University, Ghent, Belgium. · Unit of Molecular Immunology and Inflammation, Inflammation Research Center-VIB, Ghent, Belgium. · KU Leuven and Division of Rheumatology, Laboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, University Hospitals Leuven, Leuven, Belgium. ·Ann Rheum Dis · Pubmed #27474762.

ABSTRACT: -- No abstract --

4 Editorial Preface. 2014

Deodhar, Atul / van den Bosch, Filip. ·Oregon Health & Science University, Portland, OR, USA. Electronic address: deodhara@ohsu.edu. · University of Ghent, Belgium. ·Best Pract Res Clin Rheumatol · Pubmed #25488775.

ABSTRACT: -- No abstract --

5 Review Targeting the IL-23/IL-17 Pathway in Psoriasis: the Search for the Good, the Bad and the Ugly. 2018

Mylle, Sofie / Grine, Lynda / Speeckaert, Reinhart / Lambert, Jo L W / van Geel, Nanja. ·Department of Dermatology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium. · Department of Dermatology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium. Reinhart.Speeckaert@ugent.be. ·Am J Clin Dermatol · Pubmed #30003497.

ABSTRACT: New promising treatments have been developed for psoriasis that target different parts of the interleukin (IL)-23/IL-17 pathway. This approach is believed to be more disease specific, and sparing the T helper 1 pathway might prevent serious long-term adverse events. Moreover, superior Psoriasis Area and Severity Index improvements are observed, which has redefined treatment goals in psoriasis. The new molecules can be divided into different categories, according to the target: blocking agents can target the upstream cytokine IL-23 or the downstream IL-17. In the latter, a variety of targets exist, such as the ligands IL-17A and IL-17F, or a combination thereof, or a subunit of the receptor, IL-17RA. Each target seems to have its own set of advantages and pitfalls, which will impact the treatment decision in clinical practice. In this review, we summarize the current knowledge on the different inhibitors of the IL-23/IL-17 pathway. Furthermore, we briefly discuss the role of IL-17 in other diseases and comorbidities. Finally, we discuss how comprehensive knowledge is needed for the prescribing physician in order to make the most appropriate therapeutic choice for each individual patient.

6 Review Clinical management of psoriatic arthritis. 2018

Van den Bosch, Filip / Coates, Laura. ·Department of Rheumatology, Ghent University Hospital, Ghent, Belgium; VIB Center for Inflammation Research, Unit for Molecular Immunology and Inflammation, Department of Internal Medicine, Ghent University, Ghent, Belgium. Electronic address: filip.vandenbosch@ugent.be. · Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, UK. ·Lancet · Pubmed #29893227.

ABSTRACT: Psoriatic arthritis, or the broader term psoriatic disease, refers to an inflammatory disorder that affects multiple organs, including the skin and joints, and that also has related extra-articular manifestations and can have comorbidities. Patients with psoriatic disease have a substantial clinical burden. Early identification leading to timely diagnosis and treatment is crucial to prevent long-term structural damage and disability and the associated socioeconomic consequences. The increase in therapeutic options, such as disease-modifying anti-rheumatic drugs, both biological and targeted synthetic, has revolutionised the treatment of skin and joint disease, and has prompted clinicians to use the full clinical picture of an individual patient to make rational treatment decisions. Current research is also focused on treatment strategies, including treat to target, early remission-induction, and tapering.

7 Review CARD14-Mediated Activation of Paracaspase MALT1 in Keratinocytes: Implications for Psoriasis. 2017

Van Nuffel, Elien / Schmitt, Anja / Afonina, Inna S / Schulze-Osthoff, Klaus / Beyaert, Rudi / Hailfinger, Stephan. ·Unit of Molecular Signal Transduction in Inflammation, Inflammation Research Center, Ghent University-VIB, Ghent, Belgium; Department for Biomedical Molecular Biology, Ghent University, Ghent, Belgium. · Interfaculty Institute for Biochemistry, Eberhard Karls University of Tuebingen, Tuebingen, Germany. · Unit of Molecular Signal Transduction in Inflammation, Inflammation Research Center, Ghent University-VIB, Ghent, Belgium; Department for Biomedical Molecular Biology, Ghent University, Ghent, Belgium. Electronic address: rudi.beyaert@irc.vib-ugent.be. · Interfaculty Institute for Biochemistry, Eberhard Karls University of Tuebingen, Tuebingen, Germany. Electronic address: Stephan.Hailfinger@uni-tuebingen.de. ·J Invest Dermatol · Pubmed #27939769.

ABSTRACT: Mutations in caspase recruitment domain-containing protein 14(CARD14) have been linked to susceptibility to psoriasis. CARD14 is an intracellular scaffold protein that regulates proinflammatory gene expression. Recent studies have offered novel insights into the mechanisms of CARD14-mediated signaling in keratinocytes and the molecular impact of psoriasis-associated CARD14 mutations. CARD14 forms a signaling complex with BCL10 and the paracaspase MALT1, and this process is enhanced upon pathogenic CARD14 mutation, culminating in the activation of MALT1 protease activity and psoriasis-associated gene expression. This review summarizes the current knowledge of CARD14/MALT1-mediated signaling in keratinocytes and its therapeutic implications in psoriasis.

8 Review Secukinumab: IL-17A inhibition to treat psoriatic arthritis. 2016

Speeckaert, R / van Geel, N / Lambert, J / Claeys, L / Delanghe, J R / Speeckaert, M M. ·Department of Dermatology, Ghent University Hospital,Gent, Belgium. reinhart.Speeckaert@ugent.be. · Department of Dermatology, Ghent University Hospital,Gent, Belgium. · Department of Nephrology, Ghent University Hospital,Gent, Belgium. · Department of Clinical Chemistry, Ghent University Hospital,Gent, Belgium. ·Drugs Today (Barc) · Pubmed #28112279.

ABSTRACT: Interleukin-17A is an important cytokine in the pathogenesis of psoriatic arthritis. Secukinumab is a recombinant, high-affinity, fully human immunoglobulin G1kappa monoclonal antibody with a selective binding and neutralization of interleukin-17A. By providing an alternative mechanism of action to current treatments, secukinumab has shown efficacy in the key clinical domains of psoriatic arthritis. In the present paper, we discuss the role of interleukin-17A as a clinically relevant target in the treatment of psoriatic arthritis, based on preclinical findings, dose-ranging and regimen-finding, randomized, placebo-controlled clinical trials.

9 Review Recommendations for managing a suboptimal response to biologics for moderate-to-severe psoriasis: A Belgian perspective. 2016

de la Brassinne, Michel / Ghislain, Pierre-Dominique / Lambert, Jo L W / Lambert, Julien / Segaert, Siegfried / Willaert, Fabienne. ·a Department of Dermatology , Centre Hospitalier Universitaire de Liège , Liège , Belgium . · b Department of Dermatology , Clinical Research, Cliniques Saint-Luc, Université Catholique de Louvain , Brussels , Belgium . · c Department of Dermatology , University of Ghent , Ghent , Belgium . · d Department of Dermatology , University Hospital of Antwerp, University of Antwerp , Antwerp , Belgium . · e Department of Dermatology , University Hospitals Leuven , Leuven , Belgium , and. · f Department of Dermatology , Erasme University Hospital , Brussels , Belgium. ·J Dermatolog Treat · Pubmed #26415615.

ABSTRACT: Over the past decade, biologics have become the gold standard in the treatment of moderate-to-severe psoriasis for patients who have failed or who have contraindications to traditional systemic treatments. However, although practical recommendations on how to treat a suboptimal response to biologics exist in other chronic inflammatory diseases, they are only just beginning to emerge for psoriasis. This article aims to formulate recommendations in the case of a suboptimal response of psoriasis to biologics in the Belgian setting. A Belgian taskforce of psoriasis experts was convened to review the results of a literature search and formulate recommendations based on the available evidence and provide expert opinion to address gaps in the evidence. The taskforce has proposed a treatment algorithm for patients with a primary non-response or a secondary loss of response to help address an unmet need. Expert recommendations have been developed to address treatment strategies in case of a primary or secondary suboptimal response to biologics in the treatment of moderate-to-severe psoriasis in Belgium.

10 Review Practical guidance on immunogenicity to biologic agents used in the treatment of psoriasis: What can be learnt from other diseases? 2015

Lambert, Jo / Nast, Alexander / Nestle, Frank O / Prinz, Jörg C. ·a Department of Dermatology , Ghent University Hospital , Ghent , Belgium . · b Division of Evidence Based Medicine (dEBM), Department of Dermatology, Venerology and Allergy , Charité - Universitätsmedizin Berlin , Berlin , Germany . · c St. John's Institute of Dermatology, King's College London School of Medicine , London , UK , and. · d Clinic and Policlinic for Dermatology and Allergology, Ludwig-Maximilian-University , Munich , Germany. ·J Dermatolog Treat · Pubmed #26108443.

ABSTRACT: The clinical efficacy of biologic agents for the treatment of moderate to severe psoriasis is well proven in clinical studies, but patients may lose response over time. Loss of response may be due to immunogenicity and the formation of anti-drug antibodies (ADA). Although data on the immunogenicity of drugs used to treat psoriasis are now emerging, more information on the impact of factors, such as dosing regimens and concomitant immunosuppressive therapy is needed. Exploring research from other disease areas where immunogenicity has long been recognised as a significant clinical issue may help in developing future strategies for using drug level and ADA measurements to help tailor biologic therapy to meet individual needs. To this end, we analyse what is known about biologics and immunogenicity in psoriasis. In order to learn from other indications, we then address the issue of immunogenicity for three different types of biologic treatments. First, factor VIII-substitution in haemophilia, where the immune system is newly exposed to a physiologic but formerly absent protein. Second, the use of biologics in inflammatory bowel disease, where similar treatment challenges apply as observed in psoriasis. Third, immunogenicity in multiple sclerosis caused by therapeutic antibodies or interferons. Immunogenicity strategies used in other disease areas will need to be tested in psoriasis before they can be widely adopted in routine clinical practice.

11 Review An inflammatory triangle in psoriasis: TNF, type I IFNs and IL-17. 2015

Grine, Lynda / Dejager, Lien / Libert, Claude / Vandenbroucke, Roosmarijn E. ·Inflammation Research Center, VIB, Ghent, Belgium; Department Biomedical Molecular Biology, Ghent University, Ghent, Belgium. ·Cytokine Growth Factor Rev · Pubmed #25434285.

ABSTRACT: Psoriasis is a skin disease where various cytokines play a detrimental role, yet our understanding of the disease is still limited. TNF is a validated drug target in psoriasis and other autoimmune diseases, but its use is associated with side effects. Some paradoxical side effects of anti-TNF treatment are supposedly associated with type I IFNs, which are also implicated in the pathogenesis of psoriasis. Recently, the IL-23/IL-17 axis has been associated with psoriasis as well, and new drugs targeting this axis have already been developed. Findings suggest that these cytokines are interwoven. We discuss recent findings reinforcing the role of TNF, Type I IFNs and IL-17 in the pathogenesis of psoriasis and the apparent inflammatory interplay between these three cytokines.

12 Review The role of mechanical stress in the pathogenesis of spondyloarthritis and how to combat it. 2014

Jacques, Peggy / McGonagle, Dennis. ·University Hospital Ghent, De Pintelaan 185, 9000 Ghent, Belgium. · The Leeds Institute of Rheumatic and Musculoskeletal Medicine, 2nd Floor, Chapel Allerton Hospital, Chapeltown Road, Leeds LS7 4SA, UK. Electronic address: D.G.McGonagle@leeds.ac.uk. ·Best Pract Res Clin Rheumatol · Pubmed #25488779.

ABSTRACT: Given that entheses are sites of high mechanical stress that concentrate the forces of large contracting muscles down onto a small footprint of bone contact, it was recognized nearly 60 decades ago that stress and injury at such sites may play a role in the pathogenesis of mechanically related enthesopathy. In recent years, the role of mechanical stress and its related consequences on inflammatory enthesitis have also been recognized. Clinical imaging studies and experimental animal models of spondyloarthropathy including tumor necrosis factor (TNF) transgenic models and interleukin (IL)-23 overexpression systems are associated with a primary enthesitis with disease subsequently spreading to adjacent joint structures including the synovium and bone. Joint mechanical stress, without discernible microdamage or injury, leads to spondyloarthritis (SpA) in a TNF transgenic model. Normal-aged human entheses often demonstrate microdamage, but it is unclear whether an abnormal response to mechanical stress alone or the need for stress-induced microdamage is involved in human disease initiation. Clinically, the contribution of mechanical stress to SpA including psoriatic arthritis (PsA) helps conceptualize the disease in a new way and provides obvious mechanistic links to skin and nail Koebner responses. It also offers novel epidemiological explanations for why PsA develops in subjects with high body mass indices most typically in the fourth and fifth decades. Molecularly, the monogenic forms of SpA including caspase recruitment domain-containing protein 14 (CARD14) and IL36RN mutations have site-specific expression of mutated proteins in the skin, thus offering a direct molecular link between local inflammation-related pathway dysregulation and local stress or injury in disease causation. Given that many of the pathways that govern both immunity and mechanical stress including extracellular-signal-regulated kinase (ERK) and mitogen-activated protein kinase (MAPK) are shared, it may be difficult to develop strategies that selectively target mechanical stress-related pathways. However, occupational- and obesity-related factors may be potentially modifiable in susceptible individuals to prevent or ameliorate disease.

13 Review Cancer risk in immune-mediated inflammatory diseases (IMID). 2013

Beyaert, Rudi / Beaugerie, Laurent / Van Assche, Gert / Brochez, Lieve / Renauld, Jean-Christophe / Viguier, Manuelle / Cocquyt, Veronique / Jerusalem, Guy / Machiels, Jean-Pascal / Prenen, Hans / Masson, Pierre / Louis, Edouard / De Keyser, Filip. ·Department of Rheumatology, Ghent University, 0K12, De Pintelaan 185, Ghent B-9000, Belgium. filip.dekeyser@ugent.be. ·Mol Cancer · Pubmed #23987103.

ABSTRACT: Inflammation and cancer have a profound yet ambiguous relationship. Inflammation - especially chronic inflammation - has protumorigenic effects, but inflammatory cells also mediate an immune response against the tumor and immunosuppression is known to increase the risk for certain tumors.This article reviews current literature on the role of inflammation in cancer and the cancer risk in immune-mediated inflammatory diseases (IMIDs). We discuss the effect on cancer risk of different drug classes used in the treatment of IMIDs treatment, including biologicals such as tumor necrosis factor (TNF) inhibitors.Overall cancer incidence and mortality risk are similar to the general population in inflammatory bowel disease (IBD), and slightly increased for rheumatoid arthritis and psoriasis, with risk profiles differing for different tumor types. Increased risk for non-melanoma skin cancer is associated with thiopurine treatment in IBD, with the combination of anti-TNF and methotrexate in rheumatoid arthritis and with PUVA, cyclosporine and anti-TNF treatment in psoriasis. Data on the safety of using biologic or immunosuppressant therapy in IMID patients with a history of cancer are scarce.This review provides clinicians with a solid background to help them in making decisions about treatment of immune-mediated diseases in patients with a tumor history.This article is related to another review article in Molecular Cancer: http://www.molecular-cancer.com/content/12/1/86.

14 Review Therapy for spondyloarthritis: the role of extra-articular manifestations (eye, skin). 2012

Carron, Philippe / Van Praet, Liesbet / Jacques, Peggy / Elewaut, Dirk / Van den Bosch, Filip. ·Department of Rheumatology, Ghent University Hospital, Ghent 9000, Belgium. ·Rheum Dis Clin North Am · Pubmed #23083757.

ABSTRACT: Spondyloarthritis can be considered one of the prototypes (besides rheumatoid arthritis) of an inflammatory rheumatic disease. The locomotor system is prominently involved with arthritis, enthesitis, dactylitis, sacroiliitis, and/or axial disease; but besides the rheumatologic component, other body systems are frequently affected. Extra-articular manifestations are all the medical conditions and symptoms that are not directly related to the locomotor system. Besides inflammatory bowel diseases, the major concept-related extra-articular manifestations are located in the eye (acute anterior uveitis) and the skin (psoriasis). This review focuses on the possible implications of these nonrheumatologic manifestations regarding the treatment of spondyloarthritis.

15 Review New insights in segmental vitiligo: case report and review of theories. 2012

van Geel, N / Mollet, I / Brochez, L / Dutré, M / De Schepper, S / Verhaeghe, E / Lambert, J / Speeckaert, R. ·Department of Dermatology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium. Nanja.vangeel@UGent.be ·Br J Dermatol · Pubmed #21936857.

ABSTRACT: Segmental vitiligo and generalized vitiligo are in general considered to be separate entities. The aetiopathogenesis of segmental vitiligo remains unclear, although several hypotheses have been put forward including mainly neuronal mechanisms. The typical association with other autoimmune diseases, as seen in generalized vitiligo, seems to be significantly less in segmental vitiligo, although recent insights point towards a possible immune-mediated overlap between the two subtypes. In this article, we describe a case with simultaneous presence of segmental vitiligo, alopecia areata, psoriasis and a halo naevus. To our knowledge, this is the first case with this exceptional combination. This concomitant presence could support the involvement of a shared autoimmune-mediated process, and may provide new insights into the pathogenesis of segmental vitiligo and direct future research. In the light of this remarkable case, different possible aetiopathogenetic mechanisms leading to the clinical presentation of segmental vitiligo are discussed and a new three-step theory is proposed.

16 Review Vaccinations in patients with immune-mediated inflammatory diseases. 2010

Rahier, Jean-François / Moutschen, Michel / Van Gompel, Alfons / Van Ranst, Marc / Louis, Edouard / Segaert, Siegfried / Masson, Pierre / De Keyser, Filip. ·Department of Rheumatology, Ghent University Hospital, Ghent, Belgium. ·Rheumatology (Oxford) · Pubmed #20591834.

ABSTRACT: Patients with immune-mediated inflammatory diseases (IMID) such as RA, IBD or psoriasis, are at increased risk of infection, partially because of the disease itself, but mostly because of treatment with immunomodulatory or immunosuppressive drugs. In spite of their elevated risk for vaccine-preventable disease, vaccination coverage in IMID patients is surprisingly low. This review summarizes current literature data on vaccine safety and efficacy in IMID patients treated with immunosuppressive or immunomodulatory drugs and formulates best-practice recommendations on vaccination in this population. Especially in the current era of biological therapies, including TNF-blocking agents, special consideration should be given to vaccination strategies in IMID patients. Clinical evidence indicates that immunization of IMID patients does not increase clinical or laboratory parameters of disease activity. Live vaccines are contraindicated in immunocompromized individuals, but non-live vaccines can safely be given. Although the reduced quality of the immune response in patients under immunotherapy may have a negative impact on vaccination efficacy in this population, adequate humoral response to vaccination in IMID patients has been demonstrated for hepatitis B, influenza and pneumococcal vaccination. Vaccination status is best checked and updated before the start of immunomodulatory therapy: live vaccines are not contraindicated at that time and inactivated vaccines elicit an optimal immune response in immunocompetent individuals.

17 Clinical Trial Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active psoriatic arthritis (EQUATOR): results from a randomised, placebo-controlled, phase 2 trial. 2018

Mease, Philip / Coates, Laura C / Helliwell, Philip S / Stanislavchuk, Mykola / Rychlewska-Hanczewska, Anna / Dudek, Anna / Abi-Saab, Walid / Tasset, Chantal / Meuleners, Luc / Harrison, Pille / Besuyen, Robin / Van der Aa, Annegret / Mozaffarian, Neelufar / Greer, Joy M / Kunder, Rebecca / Van den Bosch, Filip / Gladman, Dafna D. ·Swedish-Providence-St Joseph Health Systems, Seattle WA, USA; University of Washington, Seattle, WA, USA. Electronic address: pmease@philipmease.com. · Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK. · Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, UK. · National Pirogov Memorial Medical University, Vinnytsya, Ukraine. · Ai Centrum Medyczne, Poznan, Poland. · Centrum Medyczne AMED, Warszawa, Poland. · Galapagos NV, Mechelen, Belgium. · Galapagos BV, Leiden, Netherlands. · Gilead Sciences, Foster City, CA, USA. · Ghent University Hospital, Ghent, Belgium; VIB-UGent Center for Inflammation Research, Ghent University, Ghent, Belgium. · University of Toronto and Krembil Research Institute, Toronto Western Hospital, Toronto, Canada. ·Lancet · Pubmed #30360969.

ABSTRACT: BACKGROUND: The Janus kinase 1 (JAK1) pathway has been implicated in the pathogenesis of psoriatic arthritis. We aimed to investigate the efficacy and safety of filgotinib, a selective JAK1 inhibitor, for the treatment of psoriatic arthritis. METHODS: The EQUATOR trial was a randomised, double-blind, placebo-controlled phase 2 trial that enrolled adults from 25 sites in seven countries (Belgium, Bulgaria, Czech Republic, Estonia, Poland, Spain, and Ukraine). Patients (aged ≥18 years) had active moderate-to-severe psoriatic arthritis (defined as at least five swollen joints and at least five tender joints) fulfilling Classification for psoriatic arthritis (CASPAR) criteria, active or a documented history of plaque psoriasis, and an insufficient response or intolerance to at least one conventional synthetic disease-modifying anti-rheumatic drug (csDMARD). Patients continued to take csDMARDs during the study if they had received this treatment for at least 12 weeks before screening and were on a stable dose for at least 4 weeks before baseline. Using an interactive web-based system, we randomly allocated patients (1:1) to filgotinib 200 mg or placebo orally once daily for 16 weeks (stratified by current use of csDMARDs and previous use of anti-tumour necrosis factor). Patients, study team, and sponsor were masked to treatment assignment. The primary endpoint was proportion of patients achieving 20% improvement in American College of Rheumatology response criteria (ACR20) at week 16 in the full analysis set (patients who received at least one dose of study drug), which was compared between groups with the Cochran-Mantel-Haenszel test and non-responder imputation method. This trial is registered with ClincalTrials.gov, number NCT03101670. FINDINGS: Between March 9, and Sept 27, 2017, 191 patients were screened and 131 were randomly allocated to treatment (65 to filgotinib and 66 to placebo). 60 (92%) patients in the filgotinib group and 64 (97%) patients in the placebo group completed the study; five patients (8%) in the filgotinib group and two patients (3%) in the placebo group discontinued treatment. 52 (80%) of 65 patients in the filgotinib group and 22 (33%) of 66 in the placebo group achieved ACR20 at week 16 (treatment difference 47% [95% CI 30·2-59·6], p<0·0001). 37 (57%) patients who received filgotinib and 39 (59%) patients who received placebo had at least one treatment-emergent adverse event. Six participants had an event that was grade 3 or worse. The most common events were nasopharyngitis and headache, occurring at similar proportions in each group. One serious treatment-emergent adverse event was reported in each group (pneumonia and hip fracture after a fall), one of which (pneumonia) was fatal in the filgotinib group. INTERPRETATION: Filgotinib is efficacious for the treatment of active psoriatic arthritis, and no new safety signals were identified. FUNDING: Galapagos and Gilead Sciences.

18 Clinical Trial Rheumatoid arthritis and psoriatic arthritis synovial fluids stimulate prolactin production by macrophages. 2017

Tang, Man Wai / Garcia, Samuel / Malvar Fernandez, Beatriz / Gerlag, Danielle M / Tak, Paul-Peter / Reedquist, Kris A. ·Department of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; m.w.tang@amc.uva.nl. · Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · Department of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · GlaxoSmithKline, Cambridge, United Kingdom. · GlaxoSmithKline, Stevenage, United Kingdom. · Department of Rheumatology, Ghent University, Ghent, Belgium; and. · Department of Rheumatology, University of Cambridge, Cambridge, United Kingdom. ·J Leukoc Biol · Pubmed #28642278.

ABSTRACT: Prolactin (PRL) is a neuroendocrine hormone that can promote inflammation. We examined the synovial tissue and fluid levels of PRL in patients with inflammatory arthritis, PRL expression in differentiated Mϕs from patients with arthritis and from healthy donors, and the effects of different stimuli on PRL production by Mϕs. PRL levels were measured in paired synovial fluid (SF) and peripheral blood of patients with rheumatoid arthritis (RA,

19 Clinical Trial Early Disease Activity or Clinical Response as Predictors of Long-Term Outcomes With Certolizumab Pegol in Axial Spondyloarthritis or Psoriatic Arthritis. 2017

van der Heijde, D / Deodhar, A / Fleischmann, R / Mease, P J / Rudwaleit, M / Nurminen, T / Davies, O. ·Leiden University Medical Center, Leiden, The Netherlands. · Oregon Health and Science University, Portland. · University of Texas SW Medical Center, Dallas. · Swedish Medical Center and University of Washington, Seattle. · Klinikum Bielefeld and Charité Berlin, Berlin, Germany, and Ghent University, Ghent, Belgium. · UCB Pharma, Monheim, Germany. · UCB Pharma, Slough, UK. ·Arthritis Care Res (Hoboken) · Pubmed #27696727.

ABSTRACT: OBJECTIVE: Early identification of patients unlikely to achieve good long-term disease control with anti-tumor necrosis factor therapy in axial spondyloarthritis (SpA) and psoriatic arthritis (PsA) is important for physicians following treat-to-target recommendations. Here we assess associations between disease activity or clinical response during the first 12 weeks of treatment and attainment of treatment targets at week 48 in axial SpA and PsA patients receiving certolizumab pegol. METHODS: The relationship between disease activity or clinical response during the first 12 weeks of treatment and achievement of week-48 targets (for axial SpA: inactive disease based on Ankylosing Spondylitis Disease Activity Score [ASDAS] using the C-reactive protein [CRP] level, or Bath Ankylosing Spondylitis Disease Activity Index <2 with normal CRP level; and for PsA: minimal disease activity) was assessed post hoc using RAPID-axSpA and RAPID-PsA trial data. RESULTS: A clear relationship between disease activity from week 2 to 12 and achievement of week-48 treatment targets was observed in both axial SpA and PsA populations. In axial SpA, week-48 ASDAS inactive disease was achieved by 0% of patients (0 of 21) with ASDAS very high disease activity at week 12, compared to 68% of patients (34 of 50) with week-12 ASDAS inactive disease. For PsA, week-48 minimal disease activity was achieved by 0% of patients (0 of 26) with Disease Activity Score in 28 joints (DAS28) using the CRP level >5.1 at week 12, compared to 73% of patients (57 of 78) with DAS28-CRP <2.6. Similar results were observed regardless of the disease activity measure used. Clinical response at week 12 also predicted week-48 outcomes, though to a lesser extent than disease activity. CONCLUSION: Using disease activity and the clinical response state during the first 12 weeks of certolizumab pegol treatment, it was possible to identify a subset of axial SpA and PsA patients unlikely to achieve long-term treatment goals.

20 Clinical Trial Quality of life and patient benefit following transition from methotrexate to ustekinumab in psoriasis. 2017

Augustin, M / Blome, C / Paul, C / Puig, L / Luger, T / Lambert, J / Chimenti, S / Girolomoni, G / Kragballe, K / Naessens, D / Bergmans, P / Smirnov, P / Barker, J / Reich, K. ·Institute for Health Services Research in Dermatology and Nursing (IVDP), German Center for Health Services Research in Dermatology (CVderm), University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany. · Department of Dermatology, Paul Sabatier University, Toulouse, France. · Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain. · University of Münster, Münster, Germany. · Department of Dermatology, Ghent University Hospital, Ghent, Belgium. · University of Rome, Rome, Italy. · Department of Dermatology, University of Verona, Verona, Italy. · Århus University, Århus, Denmark. · Janssen Cilag NV, Beerse, Belgium. · Janssen-Cilag BV, Tilburg, The Netherlands. · Janssen Pharmaceutica NV, Moscow, Russia. · St John's Institute of Dermatology, King's College, London, UK. · Dermatologikum, Hamburg, Germany. ·J Eur Acad Dermatol Venereol · Pubmed #27515070.

ABSTRACT: BACKGROUND: TRANSIT (NCT01059773) compared immediate and gradual transition from methotrexate to ustekinumab in psoriasis patients via multiple measures, including patient-reported outcomes. OBJECTIVE: To evaluate patient perception of treatment benefits in TRANSIT. METHODS: A total of 489 psoriasis patients received ustekinumab, with immediate cessation of methotrexate (Arm 1) or 4 weeks' overlap with decreasing methotrexate dose (Arm 2). Ustekinumab was administered at weeks 0, 4, 16, 28 and 40. Dermatology Life Quality Index (DLQI), EuroQol 5-item (EQ-5D), visual analogue scale (VAS) valuation technique and patient benefit index (PBI) were employed. Mean global PBI and sub-scores were calculated from the sum of the benefit items weighted by their respective relevance at baseline. Patient-relevant benefit was defined as PBI ≥1 (scale: 0 [no benefit] to 4 [maximum benefit]). Correlations of global PBI with Psoriasis Area and Severity Index (PASI) and DLQI were examined. RESULTS: Relationships between PBI and clinical data were evaluable in 340 patients. The most important treatment goals at baseline included: 'be healed of all skin defects', 'have confidence in therapy', 'get better skin quickly' and 'regain control of the disease'. Benefit in PBI global score was achieved at week 4 by 93% of patients in Arm 1 and 91% in Arm 2. Global PBI scores increased in both Arms between weeks 4 and 52. Global PBI correlated weakly with PASI change from baseline (correlation coefficient range: -0.22 to -0.40), and moderately with DLQI (-0.29 to -0.54). Overall DLQI score was lower than baseline at all times; and the percentage of patients with an overall score of 0 or 1 increased with time. Correspondingly, EQ VAS scores increased with time. DLQI and EQ VAS results were similar between arms. CONCLUSIONS: Regardless of the strategy for transitioning from methotrexate, ustekinumab was associated with rapid and sustained improvement in patient-reported outcomes. PBI appears a suitable tool for assessing patient-relevant treatment benefits in psoriasis patients.

21 Clinical Trial Secukinumab improves patient-reported outcomes in subjects with active psoriatic arthritis: results from a randomised phase III trial (FUTURE 1). 2017

Strand, Vibeke / Mease, Philip / Gossec, Laure / Elkayam, Ori / van den Bosch, Filip / Zuazo, James / Pricop, Luminita / Mpofu, Shephard / Anonymous6420867. ·Division of Immunology/Rheumatology, Stanford University School of Medicine, Palo Alto, California, USA. · Swedish Medical Center, University of Washington, Seattle, Washington, USA. · Department of Rheumatology, Sorbonne Universités, UPMC Univ Paris 06, Institut Pierre Louis d'Epidémiologie et de Santé Publique, GRC-UPMC 08 (EEMOIS), AP-HP, Pitié Salpêtrière Hospital, Paris, France. · Department of Rheumatology, Tel Aviv Medical Center, "Sackler" Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. · Department of Rheumatology, University of Ghent, Ghent, Belgium. · Novartis Pharma AG, Basel, Switzerland. · Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA. ·Ann Rheum Dis · Pubmed #27169431.

ABSTRACT: OBJECTIVE: To evaluate the effect of secukinumab on patient-reported outcomes (PROs) in subjects with active psoriatic arthritis (PsA) in the FUTURE 1 study. METHODS: Subjects were randomised 1:1:1 to receive intravenous (i.v.) secukinumab 10 mg/kg at weeks 0, 2 and 4 followed by subcutaneous secukinumab 150 or 75 mg every 4 weeks or matching placebo until week 24. RESULTS: At week 24, subjects receiving secukinumab i.v.→150 mg or i.v.→75 mg reported greater least squares mean changes from baseline than those receiving placebo in patient global assessment of disease activity (-20.6 and -20.0 vs -7.4, respectively), patient assessment of pain (-20.8 and -20.4 vs -6.7), psoriatic arthritis quality of life (-3.5 and -3.2 vs -0.4), Dermatology Life Quality Index (-8.8 and -7.9 vs 0.7); p<0.0001 vs placebo for both secukinumab groups for above PROs and Functional Assessment of Chronic Illness Therapy-Fatigue (6.74 (p<0.05 vs placebo) and 6.03 vs 4.00); all of which well exceeded minimum clinically important differences. CONCLUSIONS: In subjects with PsA, secukinumab treatment resulted in clinically meaningful improvements in global disease activity, pain, generic and disease-specific measures of health-related quality of life and fatigue. TRIAL REGISTRATION NUMBER: NCT01392326; Results.

22 Clinical Trial A Phase III, Randomized, Controlled Trial of Apremilast in Patients with Psoriatic Arthritis: Results of the PALACE 2 Trial. 2016

Cutolo, Maurizio / Myerson, Gary E / Fleischmann, Roy M / Lioté, Frédéric / Díaz-González, Federico / Van den Bosch, Filip / Marzo-Ortega, Helena / Feist, Eugen / Shah, Kamal / Hu, ChiaChi / Stevens, Randall M / Poder, Airi. ·From the Research Laboratory and Division of Clinical Rheumatology, University of Genoa, Genoa, Italy; Arthritis and Rheumatology of Georgia, Atlanta, Georgia; Metroplex Clinical Research Center, Dallas, Texas, USA; AP-HP, Hôpital Lariboisière, Rheumatology Department, Université Paris Diderot, Paris, France; University of La Laguna, Hospital Universitario de Canarias, La Laguna, Spain; UZ Gent, Ghent, Belgium; UK National Institute for Health Research (NIHR) Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals Trust and Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK; Charité - Universitätsmedizin Berlin, Department for Rheumatology and Clinical Immunology, Berlin, Germany; Celgene Corp., Summit, New Jersey, USA; Clinical Research Centre Ltd., Tartu, Estonia.M. Cutolo, MD, University of Genoa; G.E. Myerson, MD, Arthritis and Rheumatology of Georgia; R.M. Fleischmann, MD, Metroplex Clinical Research Center; F. Lioté, MD, AP-HP, Hôpital Lariboisière, Université Paris Diderot; F. Diaz-González, MD, University of La Laguna, Hospital Universitario de Canarias; F. Van den Bosch, MD, UZ Gent; H. Marzo-Ortega, MD, NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals Trust and Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds; E. Feist, MD, Charité - Universitätsmedizin Berlin; K. Shah, MD, Celgene Corp.; C. Hu, EdM, MS, Celgene Corp.; R.M. Stevens, MD, Celgene Corp.; A. Poder, MD, Clinical Research Centre Ltd. ·J Rheumatol · Pubmed #27422893.

ABSTRACT: OBJECTIVE: Apremilast, an oral phosphodiesterase 4 inhibitor, downregulates intracellular inflammatory mediator synthesis by elevating cyclic adenosine monophosphate levels. The PALACE 2 trial evaluated apremilast efficacy and safety in patients with active psoriatic arthritis (PsA) despite prior conventional disease-modifying antirheumatic drugs and/or biologic therapy. METHODS: Eligible patients were randomized (1:1:1) to placebo, apremilast 20 mg BID, or apremilast 30 mg BID. At Week 16, patients with swollen and tender joint count improvement < 20% entered early escape, with placebo patients rerandomized (1:1) to apremilast 20 mg BID or 30 mg BID while apremilast patients continued on their initial apremilast dose. At Week 24, patients remaining on placebo were rerandomized to apremilast 20 mg BID or 30 mg BID. The primary endpoint was the proportion of patients achieving > 20% improvement in American College of Rheumatology response criteria (ACR20) at Week 16. RESULTS: In the intent-to-treat population (N = 484), ACR20 at Week 16 was achieved by more patients receiving apremilast 20 mg BID [37.4% (p = 0.0002)] and 30 mg BID [32.1% (p = 0.0060)] versus placebo (18.9%). Clinically meaningful improvements in signs and symptoms of PsA, physical function, and psoriasis were observed with apremilast through Week 52. The most common adverse events were diarrhea, nausea, headache, and upper respiratory tract infection. Diarrhea and nausea generally occurred early and usually resolved spontaneously with continued treatment. Laboratory abnormalities were infrequent and transient. CONCLUSION: Apremilast demonstrated clinical improvements in PsA for up to 52 weeks, including signs and symptoms, physical function, and psoriasis. No new safety signals were observed. ClinicalTrials.gov identifier: NCT01212757.

23 Clinical Trial Effectiveness of adalimumab in treating patients with active psoriatic arthritis and predictors of good clinical responses for arthritis, skin and nail lesions. 2010

Van den Bosch, F / Manger, B / Goupille, P / McHugh, N / Rødevand, E / Holck, P / van Vollenhoven, R F / Leirisalo-Repo, M / Fitzgerald, O / Kron, M / Frank, M / Kary, S / Kupper, H. ·University Hospital Gent, Belgium. filip.vandenbosch@ugent.be ·Ann Rheum Dis · Pubmed #19815494.

ABSTRACT: OBJECTIVES: To evaluate the effectiveness of adalimumab in patients with psoriatic arthritis (PsA) and identify predictors of good clinical response for joint and skin lesions. METHODS: Patients received adalimumab 40 mg every other week in addition to standard therapy in this prospective, 12-week, open-label, uncontrolled study. Four definitions of good clinical response were used: > or =50% improvement in American College of Rheumatology response criteria (ACR50), good response according to European League Against Rheumatism (EULAR) guidelines, a > or =3-grade improvement in Physician Global Assessment of psoriasis (PGA) and a > or =50% improvement in the Nail Psoriasis Severity Index (NAPSI). Response predictors were determined by logistic regression with backward elimination (selection level was 5%). RESULTS: Of 442 patients, 94% completed 12 weeks of treatment. At week 12, 74%, 51% and 32% of the patients had achieved ACR20, 50 and 70, respectively; 87% and 61% experienced moderate and good responses according to EULAR criteria, respectively. The percentage of patients with PGA results of "clear/almost clear" increased from 34% (baseline) to 68%. The mean NAPSI score was reduced by 44%. No new safety signals were detected. A lower Health Assessment Questionnaire Disability Index (HAQ-DI) score, greater pain assessment, male sex and absence of systemic glucocorticoid therapy were strongly associated with achievement of ACR50 and good response according to EULAR criteria. In addition, greater C-reactive protein concentration and polyarthritis predicted ACR50, and non-involvement of large joints predicted a good response according to EULAR criteria. CONCLUSIONS: Adalimumab was effective in patients with PsA. Lower impairment of physical function, greater pain, male sex and no systemic treatment with glucocorticoids were factors that increased the chance of achieving a good clinical response.

24 Article The Role of the Microbiome in Gut and Joint Inflammation in Psoriatic Arthritis and Spondyloarthritis. 2018

Gilis, Elisabeth / Mortier, Céline / Venken, Koen / Debusschere, Karlijn / Vereecke, Lars / Elewaut, Dirk. ·From the Laboratory for Molecular Immunology and Inflammation, Department of Rheumatology, University Hospital Ghent; the Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research (IRC), Ghent, Belgium. · E. Gilis, MSc, Laboratory for Molecular Immunology and Inflammation, Department of Rheumatology, University Hospital Ghent, and VIB IRC; C. Mortier, DVM, Laboratory for Molecular Immunology and Inflammation, Department of Rheumatology, University Hospital Ghent, and VIB IRC; K. Venken, PhD, Laboratory for Molecular Immunology and Inflammation, Department of Rheumatology, University Hospital Ghent, and VIB IRC; K. Debusschere, DVM, Laboratory for Molecular Immunology and Inflammation, Department of Rheumatology, University Hospital Ghent, and VIB IRC; L. Vereecke, PhD, Laboratory for Molecular Immunology and Inflammation, Department of Rheumatology, University Hospital Ghent, and VIB IRC; D. Elewaut, MD, PhD, Professor, Laboratory for Molecular Immunology and Inflammation, Department of Rheumatology, University Hospital Ghent, and VIB IRC. · From the Laboratory for Molecular Immunology and Inflammation, Department of Rheumatology, University Hospital Ghent; the Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research (IRC), Ghent, Belgium. Dirk.Elewaut@ugent.be. · E. Gilis, MSc, Laboratory for Molecular Immunology and Inflammation, Department of Rheumatology, University Hospital Ghent, and VIB IRC; C. Mortier, DVM, Laboratory for Molecular Immunology and Inflammation, Department of Rheumatology, University Hospital Ghent, and VIB IRC; K. Venken, PhD, Laboratory for Molecular Immunology and Inflammation, Department of Rheumatology, University Hospital Ghent, and VIB IRC; K. Debusschere, DVM, Laboratory for Molecular Immunology and Inflammation, Department of Rheumatology, University Hospital Ghent, and VIB IRC; L. Vereecke, PhD, Laboratory for Molecular Immunology and Inflammation, Department of Rheumatology, University Hospital Ghent, and VIB IRC; D. Elewaut, MD, PhD, Professor, Laboratory for Molecular Immunology and Inflammation, Department of Rheumatology, University Hospital Ghent, and VIB IRC. Dirk.Elewaut@ugent.be. ·J Rheumatol Suppl · Pubmed #29858352.

ABSTRACT: Spondyloarthritis (SpA) encompasses a group of diseases characterized by an inflammatory arthritis involving both joints and entheses. However, extraarticular symptoms constitute a large element of the pathology and should not be underestimated. Microscopic gut inflammation is observed in 50% of patients with SpA and has been linked to disease activity, underscoring the effect of gut inflammation in SpA. In this review, we discuss the influence of gut microbiota on SpA pathogenesis. A change in microbiota composition has been linked to the development of various inflammatory arthritides, and dysbiosis is a potential factor in the pathogenesis of multiple inflammatory diseases. In this context, several groups have reported the modulatory effects of gut microbiota-derived metabolites on the effect of immune cells. The gut mucosa is populated by several types of regulatory T cells, but also some specialized unconventional innate-like T cells. These cells are predominantly found at mucosal and epithelial barrier sites, where they serve an essential role in modulating host-microbial interplay. Apart from the close association between the composition of the microbiota and inflammatory diseases, the therapeutic value of dysbiosis needs further investigation, and the identification of a causal inflammatory pathway between gut dysbiosis and musculoskeletal inflammation could revolutionize the therapeutic approach in SpA.

25 Article Towards the development of a RNAi-based topical treatment for psoriasis: Proof-of-concept in a 3D psoriasis skin model. 2018

Desmet, Eline / Van Gele, Mireille / Grine, Lynda / Remaut, Katrien / Lambert, Jo. ·Department of Dermatology, Ghent University Hospital, Ghent, Belgium. · Department of Pharmaceutics, Ghent University, Ghent, Belgium. ·Exp Dermatol · Pubmed #28833576.

ABSTRACT: RNA interference has emerged as a powerful tool for therapeutic gene silencing, as it offers the possibility to silence virtually any known pathology-causing gene. However, in vivo delivery of RNAi molecules is hampered by their unfavourable physicochemical characteristics and susceptibility to degradation by endogenous enzymes. To overcome these limitations, we recently developed an elastic liposomal formulation, called DDC642, as topical delivery system of therapeutic RNAi molecules for skin disorders. In this study, we validated the therapeutic efficacy of DDC642-encapsulated RNAi molecules in the treatment of psoriasis using 3 different in vitro models: a standardized keratinocyte monolayer culture, psoriasis-induced keratinocytes and a psoriasis-reconstructed skin model. Four genes (IL22RA1, KRT17, DEFB4 and TSLP), known to be upregulated in psoriatic lesions, and thereby key players in psoriasis pathogenesis were selected. Moreover, the possibility of using a combined siRNA therapy in the topical treatment of psoriasis was explored. Results indicate a successful gene silencing of each different target, both at mRNA and protein levels. Additionally, siRNA-DDC642 treatment resulted in a reduced expression of specific psoriasis markers, indicating their potential in future therapeutic approach. The examined siRNA combination (ie simultaneous knockdown of KRT17, DEFB4 and TSLP) showed an enhanced reduction in TSLP expression, whereas the decrease in K17 protein expression was impaired in psoriatic keratinocytes. Although the here examined siRNA combination could still be further improved, our study proved already in vitro the clinical potential of targeting multiple genes at once, each playing a different role in a complex disease such as psoriasis.

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