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Psoriasis: HELP
Articles from Cambridgeshire
Based on 45 articles published since 2008
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These are the 45 published articles about Psoriasis that originated from Cambridgeshire during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Editorial Residents'corner January/February 2016. Editorial: What's new this month? 2016

Villani, Axel-Patrice / Behle, Valeria / Cabete, Joana / Durack, Alana / Kuonen, François / Martin-Gorgojo, Alejandro. ·Dermatology Department, Hôpital Edouard Herriot, Lyon, France. · Department of Dermatology, Venerology and Allergology, University Hospital Wuerzburg, Joseph-Schneider-Str. 2, 97080 Wuerzburg, Germany. · Dermatology Department. Hospital de Santo António dos Capuchos - Centro Hospitalar de Lisboa Central. Alameda Santo António dos Capuchos 1169-050, Lisbon, Portugal. · Dermatology Department, Box 46, Addenbrooke's Hospital, Hills road, Cambridge, CB2 OQQ, UK. · Department of Dermatology and Venereology, Hôpital de Beaumont, Lausanne University Hospital Center, Av. de Beaumont 29, CH-1011 Lausanne, Switzerland. · Dermatology Department, General University Hospital "Gregorio Marañon", C/ Doctor Esquerdo 46, and Clinica Dermatologica Internacional and Clinica Ruber, Madrid, Spain. ·Eur J Dermatol · Pubmed #27023019.

ABSTRACT: -- No abstract --

2 Editorial Psoriasis: More Than Just Skin Deep. 2015

Tarkin, Jason M / Rudd, James H F. ·From the Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, UK. · From the Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, UK. jhfr2@cam.ac.uk. ·Arterioscler Thromb Vasc Biol · Pubmed #26607356.

ABSTRACT: -- No abstract --

3 Editorial Residents' corner June 2015. Editorial: What's new this month? 2015

Cabete, Joana / Behle, Valeria / Villani, Axel-Patrice / Durack, Alana / Kuonen, François / Martin-Gorgojo, Alejandro. ·Dermatology Department. Hospital de Santo António dos Capuchos - Centro Hospitalar de Lisboa Central. Alameda Santo António dos Capuchos 1169-050, Lisbon, Portugal. · Department of Dermatology, Venerology and Allergology, University Hospital Wuerzburg, Joseph-Schneider-Str. 2, 97080 Wuerzburg, Germany. · Dermatology Department, Hôpital Edouard Herriot, Lyon, France. · Dermatology department, Box 46, Addenbrooke's Hospital, Hills road, Cambridge, CB2 0QQ, UK. · Department of Dermatology and Venereology, Hôpital de Beaumont, Lausanne University Hospital Center, Av. de Beaumont 29, CH-1011 Lausanne, Switzerland. · Dermatology Department. General University Hospital Gregorio Marañon. C/ Doctor Esquerdo 46, 28007 Madrid, Spain. Dermatology Department. Clinica Dermatologica Internacional and Clinica Ruber. Madrid, Spain. ·Eur J Dermatol · Pubmed #26412040.

ABSTRACT: -- No abstract --

4 Review IL36RN Mutations Affect Protein Expression and Function: A Basis for Genotype-Phenotype Correlation in Pustular Diseases. 2016

Tauber, Marie / Bal, Elodie / Pei, Xue-Yuan / Madrange, Marine / Khelil, Amel / Sahel, Houria / Zenati, Akila / Makrelouf, Mohamed / Boubridaa, Khaled / Chiali, Amel / Smahi, Naima / Otsmane, Farida / Bouajar, Bakar / Marrakchi, Slaheddine / Turki, Hamida / Bourrat, Emmanuelle / Viguier, Manuelle / Hamel, Yamina / Bachelez, Hervé / Smahi, Asma. ·INSERM unit U1163, Imagine Institute, Necker-Enfants Malades Hospital, Paris, France. · Department of Biochemistry, University of Cambridge, Cambridge, UK. · Department of Dermatology, CHU Oran, Oran, Algeria. · Department of Dermatology, CHU Bab El Oued, Bab el Oued, Alger, Algeria. · Central laboratory of Biology, CHU Bab El Oued, Bab el Oued, Alger, Algeria. · Department of Dermatology and the Laboratory of Immunology, Hedi Chaker Hospital, Sfax University, Sfax, Tunisia. · Department of Dermatology, AP-HP, Saint-Louis Hospital, Paris, France. · Department of Dermatology, AP-HP, Saint-Louis Hospital, Paris, France; University Paris-Diderot, Sorbonne Paris Cité, Paris, France. · INSERM unit U1163, Imagine Institute, Necker-Enfants Malades Hospital, Paris, France; Department of Dermatology, AP-HP, Saint-Louis Hospital, Paris, France; University Paris-Diderot, Sorbonne Paris Cité, Paris, France. · INSERM unit U1163, Imagine Institute, Necker-Enfants Malades Hospital, Paris, France. Electronic address: asma.smahi@inserm.fr. ·J Invest Dermatol · Pubmed #27220475.

ABSTRACT: Homozygous or compound heterozygous IL36RN gene mutations underlie the pathogenesis of psoriasis-related pustular eruptions including generalized pustular psoriasis, palmoplantar pustular psoriasis, acrodermatitis continua of Hallopeau, and acute generalized exanthematous pustular eruption. We identified two unreported IL36RN homozygous mutations (c.41C>A/p.Ser14X and c.420_426del/p.Gly141MetfsX29) in patients with familial generalized pustular psoriasis. We analyzed the impact of a spectrum of IL36RN mutations on IL-36 receptor antagonist protein by using site-directed mutagenesis and expression in HEK293T cells. This enabled us to differentiate null mutations with complete absence of IL-36 receptor antagonist (the two previously unreported mutations, c.80T>C/p.Leu27Pro, c.28C>T/p.Arg10X, c.280G>T/p.Glu94X, c.368C>G/p.Thr123Arg, c.368C>T/p.Thr123Met, and c.227C>T/p.Pro76Leu) from mutations with decreased (c.95A>G/p.His32Arg, c.142C>T/p.Arg48Trp, and c.308C>T/p.Ser113Leu) or unchanged (c.304C>T/p.Arg102Trp and c.104A>G/p.Lys35Arg) protein expression. Functional assays measuring the impact of mutations on the capacity to repress IL-36-dependent activation of the NF-κB pathway showed complete functional impairment for null mutations, whereas partial or no impairment was observed for other mutations considered as hypomorphic. Finally, null mutations were associated with severe clinical phenotypes (generalized pustular psoriasis, acute generalized exanthematous pustular eruption), whereas hypomorphic mutations were identified in both localized (palmoplantar pustular psoriasis, acrodermatitis continua of Hallopeau) and generalized variants. These results provide a preliminary basis for genotype-phenotype correlation in patients with deficiency of the IL-36Ra (DITRA), and suggest the involvement of other factors in the modulation of clinical expression.

5 Review A Systematic Review of Factors Associated with Non-Adherence to Treatment for Immune-Mediated Inflammatory Diseases. 2015

Vangeli, Eleni / Bakhshi, Savita / Baker, Anna / Fisher, Abigail / Bucknor, Delaney / Mrowietz, Ulrich / Östör, Andrew J K / Peyrin-Biroulet, Laurent / Lacerda, Ana P / Weinman, John. ·Department of Psychology, London South Bank University, London, UK. · Psychological Medicine, King's College London, London, UK. · Atlantis Healthcare, London, UK. · University College London, London, UK. · London Metropolitan University, London, UK. · Psoriasis-Center at the Department of Dermatology, University Medical Center of Schleswig-Holstein, Campus Kiel, Germany. · School of Clinical Medicine, University of Cambridge, Cambridge, UK. · Inserm U954 and Department of Gastroenterology, Université de Lorraine, Vandoeuvre-les-Nancy, France. · AbbVie Inc, North Chicago, IL, USA. · Institute of Pharmaceutical Science, King's College London, 5th Floor, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK. John.weinman@kcl.ac.uk. ·Adv Ther · Pubmed #26547912.

ABSTRACT: BACKGROUND: Non-adherence impacts negatively on patient health outcomes and has associated economic costs. Understanding drivers of treatment adherence in immune-mediated inflammatory diseases is key for the development of effective strategies to tackle non-adherence. OBJECTIVE: To identify factors associated with treatment non-adherence across diseases in three clinical areas: rheumatology, gastroenterology, and dermatology. DESIGN: Systematic review. DATA SOURCES: Articles published in PubMed, Science Direct, PsychINFO and the Cochrane Library from January 1, 1980 to February 14, 2014. STUDY SELECTION: Studies were eligible if they included patients with a diagnosis of rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, inflammatory bowel disease, or psoriasis and included statistics to examine associations of factors with non-adherence. DATA EXTRACTION: Data were extracted by the first reviewer using a standardized 23-item form and verified by a second/third reviewer. Quality assessment was carried out for each study using a 16-item quality checklist. RESULTS: 73 studies were identified for inclusion in the review. Demographic or clinical factors were not consistently associated with non-adherence. Limited evidence was found for an association between non-adherence and treatment factors such as dosing frequency. Consistent associations with adherence were found for psychosocial factors, with the strongest evidence for the impact of the healthcare professional-patient relationship, perceptions of treatment concerns and depression, lower treatment self-efficacy and necessity beliefs, and practical barriers to treatment. CONCLUSIONS: While examined in only a minority of studies, the strongest evidence found for non-adherence were psychosocial factors. Interventions designed to address these factors may be most effective in tackling treatment non-adherence.

6 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,

7 Clinical Trial Reliability and validity of the Psoriasis Itch Visual Analog Scale in psoriasis vulgaris. 2017

Pedersen, Claus Bang / McHorney, Colleen A / Larsen, Lotte Seiding / Lophaven, Katja Wendicke / Moeller, Anders Holmen / Reaney, Matthew. ·a LEO Pharma , Ballerup , Denmark. · b ERT , Pittsburgh , PA , USA. · c ERT , Peterborough , UK. ·J Dermatolog Treat · Pubmed #27454156.

ABSTRACT: INTRODUCTION: The single-item Psoriasis Itch VAS was developed to measure itch intensity within the last 24 hours in psoriasis vulgaris to assess treatment benefit. Its psychometric properties were explored in two trials. METHODS: Data from two randomized, parallel-group phase 3 trials with subjects suffering from psoriasis vulgaris on the body (n = 426, 463) were analyzed. Cross-sectional distributional properties and construct validity of the Psoriasis Itch VAS as well as longitudinal test-retest reliability and sensitivity to change of the Psoriasis Itch VAS were investigated. All statistical tests were two-tailed. RESULTS: Across both trials, acceptable distributional properties were observed. Convergent-validity correlations between the Psoriasis Itch VAS and other patient-reported and clinician-reported outcomes provided strong endorsement for construct validity as did tests of known-groups validity. Longitudinal measurement properties, involving test-retest reliability and sensitivity to change, also offered evidence for the measurement integrity of the Psoriasis Itch VAS. DISCUSSION: Results from the assessment of validity, reliability, and sensitivity to change support the use of the Psoriasis Itch VAS to measure itch intensity in psoriasis vulgaris. Data from two trials provided evidence that the Psoriasis Itch VAS is well-defined and reliable for measuring itch in psoriasis vulgaris to assess treatment benefit (i.e. therapeutic response).

8 Clinical Trial A Randomized, Placebo-Controlled Study of SRT2104, a SIRT1 Activator, in Patients with Moderate to Severe Psoriasis. 2015

Krueger, James G / Suárez-Fariñas, Mayte / Cueto, Inna / Khacherian, Artemis / Matheson, Robert / Parish, Lawrence C / Leonardi, Craig / Shortino, Denise / Gupta, Akanksha / Haddad, Jonathan / Vlasuk, George P / Jacobson, Eric W. ·Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, United States of America. · Center for Clinical and Translational Science, The Rockefeller University, New York, New York, United States of America. · Oregon Medical Research Center, PC, Portland, Oregon, United States of America. · Paddington Testing Co, Inc., Philadelphia, Pennsylvania, United States of America. · Central Dermatology, St. Louis, Missouri, United States of America. · Clinical Statistics, GlaxoSmithKline, Research Triangle Park, North Carolina, United States of America. · Sirtris, a GlaxoSmithKline Company, Cambridge, Massachusetts, United States of America. ·PLoS One · Pubmed #26556603.

ABSTRACT: TRIAL REGISTRATION: Clinicaltrials.gov NCT01154101.

9 Article Proceedings of the 2017 GRAPPA Collaborative Research Network Meeting. 2018

Jadon, Deepak R / Chandran, Vinod / Stober, Carmel / Ogdie, Alexis / Armstrong, April W / Callis Duffin, Kristina / Gladman, Dafna D / Helliwell, Philip S / O'Sullivan, Denis / de Wit, Maarten / FitzGerald, Oliver / Ritchlin, Christopher T. ·From the Rheumatology Research Unit, Cambridge University Hospitals UK National Health Service (NHS) Foundation Trust, Cambridge; University of Leeds, Leeds; Bradford Hospitals NHS Foundation Trust, Bradford, UK; Department of Medicine, Division of Rheumatology, University of Toronto, Toronto Western Hospital, Krembil Research Institute, Toronto, Ontario, Canada; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; University of Southern California, Los Angeles, California; University of Utah, Salt Lake City, Utah; Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center, Rochester, New York, USA; Our Lady's Hospice and Care Services; Newman Clinical Research Professor, Department of Rheumatology, St. Vincent's University Hospital and Conway Institute for Biomolecular Research, University College Dublin, Dublin, Ireland; Department of Medical Humanities, VU University Medical Centre, Amsterdam, the Netherlands. deepak.jadon@addenbrookes.nhs.uk. · D.R. Jadon, MBBCh, MRCP, PhD, Director of Rheumatology Research Unit, Cambridge University Hospitals NHS Foundation Trust; V. Chandran, MBBS, MD, DM, PhD, Department of Medicine, Division of Rheumatology, University of Toronto, Toronto Western Hospital, Krembil Research Institute; C. Stober, PhD, MBChB, MRCP, Consultant Rheumatologist, Cambridge University Hospitals NHS Foundation Trust; A. Ogdie, MD, Assistant Professor of Medicine and Epidemiology, Perelman School of Medicine, University of Pennsylvania; A.W. Armstrong, MD, MPH, University of Southern California; K. Callis Duffin, MD, University of Utah; D.D. Gladman, MD, FRCPC, Professor of Medicine, University of Toronto, and Senior Scientist, Krembil Research Institute, Toronto Western Hospital; P.S. Helliwell, DM, PhD, FRCP, University of Leeds, and Bradford Hospitals NHS Foundation Trust; D. O'Sullivan, BE, Patient Research Partner, Our Lady's Hospice and Care Services; M. de Wit, PhD, Patient Research Partner, Department of Medical Humanities, VU University Medical Centre; O. FitzGerald, MD, FRCPI, FRCP( UK), Newman Clinical Research Professor, Department of Rheumatology, St. Vincent's University Hospital and Conway Institute for Biomolecular Research, University College Dublin; C.T. Ritchlin, MD, MPH, Professor of Medicine, Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center. deepak.jadon@addenbrookes.nhs.uk. · From the Rheumatology Research Unit, Cambridge University Hospitals UK National Health Service (NHS) Foundation Trust, Cambridge; University of Leeds, Leeds; Bradford Hospitals NHS Foundation Trust, Bradford, UK; Department of Medicine, Division of Rheumatology, University of Toronto, Toronto Western Hospital, Krembil Research Institute, Toronto, Ontario, Canada; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; University of Southern California, Los Angeles, California; University of Utah, Salt Lake City, Utah; Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center, Rochester, New York, USA; Our Lady's Hospice and Care Services; Newman Clinical Research Professor, Department of Rheumatology, St. Vincent's University Hospital and Conway Institute for Biomolecular Research, University College Dublin, Dublin, Ireland; Department of Medical Humanities, VU University Medical Centre, Amsterdam, the Netherlands. · D.R. Jadon, MBBCh, MRCP, PhD, Director of Rheumatology Research Unit, Cambridge University Hospitals NHS Foundation Trust; V. Chandran, MBBS, MD, DM, PhD, Department of Medicine, Division of Rheumatology, University of Toronto, Toronto Western Hospital, Krembil Research Institute; C. Stober, PhD, MBChB, MRCP, Consultant Rheumatologist, Cambridge University Hospitals NHS Foundation Trust; A. Ogdie, MD, Assistant Professor of Medicine and Epidemiology, Perelman School of Medicine, University of Pennsylvania; A.W. Armstrong, MD, MPH, University of Southern California; K. Callis Duffin, MD, University of Utah; D.D. Gladman, MD, FRCPC, Professor of Medicine, University of Toronto, and Senior Scientist, Krembil Research Institute, Toronto Western Hospital; P.S. Helliwell, DM, PhD, FRCP, University of Leeds, and Bradford Hospitals NHS Foundation Trust; D. O'Sullivan, BE, Patient Research Partner, Our Lady's Hospice and Care Services; M. de Wit, PhD, Patient Research Partner, Department of Medical Humanities, VU University Medical Centre; O. FitzGerald, MD, FRCPI, FRCP( UK), Newman Clinical Research Professor, Department of Rheumatology, St. Vincent's University Hospital and Conway Institute for Biomolecular Research, University College Dublin; C.T. Ritchlin, MD, MPH, Professor of Medicine, Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center. ·J Rheumatol Suppl · Pubmed #29858357.

ABSTRACT: The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Collaborative Research Network (CRN) is an endeavor that aims to address gaps in the knowledge of the etiopathogenesis and management of psoriatic disease by best using the large community of experienced investigators who are already collecting rich clinical phenotype data and biologic samples using validated techniques. Exemplar rheumatology and dermatology projects will inform strategies to implement the CRN, while input and funding from government organizations, charities, and industry will shape the CRN. The key immediate priorities to establish the CRN are discussed herein and include (1) strategies for building infrastructure to collect and store biosamples and associated clinical data, (2) best practices for sample collection and storage, (3) approaches to engage the GRAPPA community of investigators and industry to collaborate most effectively on shared priorities, and (4) agreement on a funding strategy. The following 4 CRN candidate flagship research areas were identified: (1) predictors of treatment response in psoriatic arthritis (PsA) and cutaneous psoriasis (PsC) to permit personalized and stratified medicine approaches; (2) predictors of structural damage and disease severity, linking with the existing PsA BioDAM project; (3) predictors of PsC progressing to PsA to enable earlier intervention and possibly halt progression to PsA; and (4) comorbidity prevalence and effect on clinical outcomes in psoriatic disease. The collaboration and momentum provided by a GRAPPA-CRN will offer more than the sum of its individual contributing centers. A CRN will permit high-quality research that can more effectively address questions pertinent to patients, clinicians, scientists, industry, and governments.

10 Article The Benefits and Challenges of Setting Up a Longitudinal Psoriatic Arthritis Database. 2018

Gladman, Dafna D / Coates, Laura C / Jadon, Deepak R / Tillett, William / Mease, Philip J / Vis, Marijn. ·From the University of Toronto; Krembil Research Institute; Psoriatic Arthritis Program University Health Network, Toronto Western Hospital, Toronto, Ontario, Canada; Department of Orthopedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford; Department of Rheumatology, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge; Royal National Hospital for Rheumatic Diseases; University of Bath, Bath, UK; Swedish Medical Center and University of Washington School of Medicine, Seattle, Washington, USA; Department of Rheumatology, Erasmus Medical Center, Rotterdam, the Netherlands. dafna.gladman@utoronto.ca. · D.D. Gladman, MD, FRCPC, Professor of Medicine, University of Toronto, and Senior Scientist, Krembil Research Institute, and Director, Psoriatic Arthritis Program University Health Network, Toronto Western Hospital; L.C. Coates, MBChB, PhD, Department of Orthopedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford; D.R. Jadon, MBBCh, MRCP, PhD, Consultant Rheumatologist, Department of Rheumatology, Cambridge University Hospitals NHS Foundation Trust; W. Tillett, MBChB, PhD, Consultant Rheumatologist, Royal National Hospital for Rheumatic Diseases, and Senior Lecturer, University of Bath; P.J. Mease, MD, Rheumatology Research, Swedish Medical Center and University of Washington School of Medicine; M. Vis, MD, Department of Rheumatology, Erasmus Medical Center, Rotterdam, the Netherlands. dafna.gladman@utoronto.ca. · From the University of Toronto; Krembil Research Institute; Psoriatic Arthritis Program University Health Network, Toronto Western Hospital, Toronto, Ontario, Canada; Department of Orthopedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford; Department of Rheumatology, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge; Royal National Hospital for Rheumatic Diseases; University of Bath, Bath, UK; Swedish Medical Center and University of Washington School of Medicine, Seattle, Washington, USA; Department of Rheumatology, Erasmus Medical Center, Rotterdam, the Netherlands. · D.D. Gladman, MD, FRCPC, Professor of Medicine, University of Toronto, and Senior Scientist, Krembil Research Institute, and Director, Psoriatic Arthritis Program University Health Network, Toronto Western Hospital; L.C. Coates, MBChB, PhD, Department of Orthopedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford; D.R. Jadon, MBBCh, MRCP, PhD, Consultant Rheumatologist, Department of Rheumatology, Cambridge University Hospitals NHS Foundation Trust; W. Tillett, MBChB, PhD, Consultant Rheumatologist, Royal National Hospital for Rheumatic Diseases, and Senior Lecturer, University of Bath; P.J. Mease, MD, Rheumatology Research, Swedish Medical Center and University of Washington School of Medicine; M. Vis, MD, Department of Rheumatology, Erasmus Medical Center, Rotterdam, the Netherlands. ·J Rheumatol Suppl · Pubmed #29858349.

ABSTRACT: The members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) have shown great interest in developing a common GRAPPA database. To address this interest, GRAPPA included a symposium at its 2017 annual meeting to examine the concepts of registries and databases. At this symposium, examples of existing databases were reviewed, and their challenges and achievements were discussed.

11 Article Patterns of peripheral joint involvement in psoriatic arthritis-Symmetric, ray and/or row? 2018

Chandran, Vinod / Stecher, Lynne / Farewell, Vern / Gladman, Dafna D. ·Departments of Medicine & Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Centre for Prognosis Studies in The Rheumatic Diseases, Krembil Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada. · Institute of Medical Statistics and Epidemiology, Klinikum rechts der Isar, Technical University of Munich, Ismaninger Strasse 22, 81675 Munich, Germany. · MRC Biostatistics Unit, Institute of Public Health, University of Cambridge, Cambridge, United Kingdom. · Centre for Prognosis Studies in The Rheumatic Diseases, Krembil Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada. Electronic address: dafna.gladman@utoronto.ca. ·Semin Arthritis Rheum · Pubmed #29724452.

ABSTRACT: OBJECTIVE: We sought to examine whether joint involvement in psoriatic arthritis (PsA) follows a symmetric, ray, and/or row pattern using longitudinal data. METHODS: Data on activity and clinical damage of the joints of the hands and feet were obtained from a PsA cohort. For each analysis (symmetry, ray or row) for each outcome (joint damage and activity) expected values for table cells under the null hypothesis that joints progress independently to damage or activity were calculated based on a logistic regression model with patient level random effects for the probability of involvement developing between clinic visits. To determine the consistency of observed with expected values, goodness-of-fit tests were performed. RESULTS: Data from 704 patients were available. The 511 (552) patients with no hand (foot) damage at clinic entry were used for analyses of hand (foot) damage. When considering joint damage, there was strong evidence against independence of joint involvement based on evident symmetric patterns. There was little suggestion of ray patterns of joint damage. There was considerable evidence for row pattern of involvement of joints. When considering joint activity, symmetric patterns were also evident but, unlike joint damage, there was evidence of ray patterns, most notably in the hands. There was also evidence for row pattern involvement. CONCLUSION: Patterns of peripheral joint involvement seen over time in PsA patients, demonstrate consistency with expected ray patterns of disease activity, especially in the hands, but there is also considerable evidence for symmetric and row patterns for both joint damage and activity.

12 Article Prevalence and predictors of tumour necrosis factor inhibitor persistence in psoriatic arthritis. 2018

Stober, Carmel / Ye, Weiyu / Guruparan, Thushyanthan / Htut, Eiphyu / Clunie, Gavin / Jadon, Deepak. ·Department of Rheumatology, Addenbrooke's Hospital. · Department of Medicine, Cambridge University Hospitals NHS FT. · School of Clinical Medicine, University of Cambridge, Cambridge, UK. ·Rheumatology (Oxford) · Pubmed #29077973.

ABSTRACT: Objectives: To evaluate TNF-α inhibitor (TNFi) persistence when used as first- or second-line biologic therapy for the management of PsA, and to determine baseline clinical and laboratory parameters associated with TNFi persistence. Methods: A retrospective single-centre cohort study was performed on all patients with PsA initiated on TNFi therapy between 2003 and 2015. Demographic, clinical and laboratory characteristics were compared with TNFi persistence, using Kaplan-Meier survival and Cox proportional hazards models. Results: One hundred and eighty-eight patients with PsA were prescribed TNFi therapy as first-line biologic therapy over a period of 635 person-years [46% male, mean (s.d.) age 47.3 (11.4) years; median (interquartile range) disease duration 11 (7-16) years]. At 12 months of follow-up 79% of patients persisted with TNFi therapy, and 73% at 24 months. Of those discontinuing TNFi, 35% stopped due to primary inefficacy, 22% secondary inefficacy and 43% adverse events. Multivariable analysis identified female sex (hazard ratio (HR) 2.57; 95% CI: 1.26, 5.24; P = 0.01) and the presence of metabolic syndrome-related co-morbidities (HR = 2.65, 95% CI: 1.24, 5.69; P = 0.01) as predictors of lower persistence. Of 32 cases treated with a second TNFi, persistence at 12 months was 56%. TNFi persistence was 2-fold less likely in these 32 cases compared with first-line TNFi users (HR = 2.02, 95% CI: 1.20, 3.42; P = 0.01). Conclusion: Patients with PsA who are female and have metabolic syndrome-related co-morbidities have lower TNFi persistence. Although persistence was lower in patients who had switched to a second TNFi, a substantial proportion of these cases responded, advocating switching to a second TNFi as a valid therapeutic strategy.

13 Article Jejunal atresia, periodic fevers and psoriatic arthropathy in Baraitser-Winter malformation syndrome. 2017

Saskin, Avi / Tischkowitz, Marc / Anonymous2650918. ·aDepartment of Medical Genetics, McGill University, Montreal, Quebec, Canada bWellcome Trust Sanger Institute cDepartment of Medical Genetics, University of Cambridge, Cambridge, UK. ·Clin Dysmorphol · Pubmed #28872563.

ABSTRACT: -- No abstract --

14 Article Proceedings of the GRAPPA 2016 Retreat. 2017

Jadon, Deepak R / Gladman, Dafna D / Mease, Philip J / FitzGerald, Oliver / Chandran, Vinod / Goel, Niti / Rosen, Cheryl F / Maksymowych, Walter P / Ritchlin, Christopher T / Ogdie, Alexis / Coates, Laura C / Cauli, Alberto / Soriano, Enrique R / Husni, M Elaine / Campbell, Willemina / Azevedo, Valderilio F / Callis Duffin, Kristina / Armstrong, April W / Gottlieb, Alice B / Kavanaugh, Arthur / Garg, Amit / Helliwell, Philip S. ·From the Rheumatology Research Unit, Cambridge University Hospitals UK National Health Service (NHS) Foundation Trust, Cambridge; UK National Institute for Health Research Clinical Lecturer, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds; Bradford Hospitals NHS Foundation Trust, Bradford, UK; Department of Medicine, Division of Rheumatology, University of Toronto, Toronto Western Hospital, Krembil Research Institute; Division of Dermatology, Toronto Western Hospital, University of Toronto, Ontario; University of Alberta, Edmonton, Alberta, Canada; Rheumatology Research, Swedish Medical Center and University of Washington School of Medicine, Seattle, Washington; Advisory Services, QuintilesIMS, Denver, Colorado; Duke University School of Medicine, Durham, North Carolina; Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center, Rochester; New York Medical College, Valhalla; Hofstra Northwell School of Medicine, New Hyde Park, New York, New York; Medicine and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Cleveland Clinic, Cleveland, Ohio; University of Utah, Salt Lake City, Utah; University of Southern California, Los Angeles; University of California at San Diego, San Diego, California, USA; Newman Clinical Research Professor, Department of Rheumatology, St. Vincent's University Hospital; Conway Institute for Biomolecular Research, University College Dublin, Dublin, Ireland; Division of Rheumatology, University of Cagliari, Cagliari, Italy, Sección Reumatología, Servicio de Clínica Médica, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; Federal University of Paraná, Curitiba, Brazil. · D.R. Jadon, MBBCh, MRCP, PhD, Director, Rheumatology Research Unit, Cambridge University Hospitals NHS Foundation Trust; D.D. Gladman, MD, FRCPC, Professor of Medicine, University of Toronto, and Senior Scientist, Krembil Research Institute, Toronto Western Hospital; P.J. Mease, MD, Rheumatology Research, Swedish Medical Center and University of Washington School of Medicine; O. FitzGerald, MD, FRCPI, FRCP( UK), Newman Clinical Research Professor, Department of Rheumatology, St. Vincent's University Hospital, and Conway Institute for Biomolecular Research, University College Dublin; V. Chandran, MBBS, MD, DM, PhD, Department of Medicine, Division of Rheumatology, University of Toronto, Toronto Western Hospital, Krembil Research Institute; N. Goel, MD, Patient Research Partner, Vice President, Advisory Services, QuintilesIMS, and Adjunct Assistant Professor, Duke University School of Medicine; C.F. Rosen, MD, FRCPC, Division of Dermatology, Toronto Western Hospital, University of Toronto; W.P. Maksymowych, MD, FRCP(C), Professor of Medicine, University of Alberta; C.T. Ritchlin, MD, MPH, Professor of Medicine, Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center; A. Ogdie, MD, Assistant Professor of Medicine and Epidemiology, Perelman School of Medicine, University of Pennsylvania; L.C. Coates, MBChB, PhD, UK National Institute for Health Research Clinical Lecturer, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds; A. Cauli, MD, PhD, Division of Rheumatology, University of Cagliari; E.R. Soriano, MD, MSC, Sección Reumatología, Servicio de Clínica Médica, Hospital Italiano de Buenos Aires; M.E. Husni, MD, MPH, Cleveland Clinic; W. Campbell, BEd LLB, Patient Research Partner, Toronto Western Hospital; V.F. Azevedo, MD, PhD, Adjunct Professor of Rheumatology, Federal University of Paraná; K. Callis Duffin, MD, University of Utah; A.W. Armstrong, MD, MPH, University of Southern California; A.B. Gottlieb, MD, PhD, Professor of Dermatology, New York Medical College; A. Kavanaugh, MD, Professor of Medicine, University of California at San Diego; A. Garg, MD, Hofstra Northwell School of Medicine; P.S. Helliwell, DM, PhD, FRCP, University of Leeds, and Bradford Hospitals NHS Foundation Trust. · From the Rheumatology Research Unit, Cambridge University Hospitals UK National Health Service (NHS) Foundation Trust, Cambridge; UK National Institute for Health Research Clinical Lecturer, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds; Bradford Hospitals NHS Foundation Trust, Bradford, UK; Department of Medicine, Division of Rheumatology, University of Toronto, Toronto Western Hospital, Krembil Research Institute; Division of Dermatology, Toronto Western Hospital, University of Toronto, Ontario; University of Alberta, Edmonton, Alberta, Canada; Rheumatology Research, Swedish Medical Center and University of Washington School of Medicine, Seattle, Washington; Advisory Services, QuintilesIMS, Denver, Colorado; Duke University School of Medicine, Durham, North Carolina; Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center, Rochester; New York Medical College, Valhalla; Hofstra Northwell School of Medicine, New Hyde Park, New York, New York; Medicine and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Cleveland Clinic, Cleveland, Ohio; University of Utah, Salt Lake City, Utah; University of Southern California, Los Angeles; University of California at San Diego, San Diego, California, USA; Newman Clinical Research Professor, Department of Rheumatology, St. Vincent's University Hospital; Conway Institute for Biomolecular Research, University College Dublin, Dublin, Ireland; Division of Rheumatology, University of Cagliari, Cagliari, Italy, Sección Reumatología, Servicio de Clínica Médica, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; Federal University of Paraná, Curitiba, Brazil. p.helliwell@leeds.ac.uk. · D.R. Jadon, MBBCh, MRCP, PhD, Director, Rheumatology Research Unit, Cambridge University Hospitals NHS Foundation Trust; D.D. Gladman, MD, FRCPC, Professor of Medicine, University of Toronto, and Senior Scientist, Krembil Research Institute, Toronto Western Hospital; P.J. Mease, MD, Rheumatology Research, Swedish Medical Center and University of Washington School of Medicine; O. FitzGerald, MD, FRCPI, FRCP( UK), Newman Clinical Research Professor, Department of Rheumatology, St. Vincent's University Hospital, and Conway Institute for Biomolecular Research, University College Dublin; V. Chandran, MBBS, MD, DM, PhD, Department of Medicine, Division of Rheumatology, University of Toronto, Toronto Western Hospital, Krembil Research Institute; N. Goel, MD, Patient Research Partner, Vice President, Advisory Services, QuintilesIMS, and Adjunct Assistant Professor, Duke University School of Medicine; C.F. Rosen, MD, FRCPC, Division of Dermatology, Toronto Western Hospital, University of Toronto; W.P. Maksymowych, MD, FRCP(C), Professor of Medicine, University of Alberta; C.T. Ritchlin, MD, MPH, Professor of Medicine, Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center; A. Ogdie, MD, Assistant Professor of Medicine and Epidemiology, Perelman School of Medicine, University of Pennsylvania; L.C. Coates, MBChB, PhD, UK National Institute for Health Research Clinical Lecturer, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds; A. Cauli, MD, PhD, Division of Rheumatology, University of Cagliari; E.R. Soriano, MD, MSC, Sección Reumatología, Servicio de Clínica Médica, Hospital Italiano de Buenos Aires; M.E. Husni, MD, MPH, Cleveland Clinic; W. Campbell, BEd LLB, Patient Research Partner, Toronto Western Hospital; V.F. Azevedo, MD, PhD, Adjunct Professor of Rheumatology, Federal University of Paraná; K. Callis Duffin, MD, University of Utah; A.W. Armstrong, MD, MPH, University of Southern California; A.B. Gottlieb, MD, PhD, Professor of Dermatology, New York Medical College; A. Kavanaugh, MD, Professor of Medicine, University of California at San Diego; A. Garg, MD, Hofstra Northwell School of Medicine; P.S. Helliwell, DM, PhD, FRCP, University of Leeds, and Bradford Hospitals NHS Foundation Trust. p.helliwell@leeds.ac.uk. ·J Rheumatol · Pubmed #28461522.

ABSTRACT: In advance of its 2016 annual meeting, members of the steering committee of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) convened for a strategic planning meeting. The purpose of this advance meeting was to review the work of GRAPPA since its inception in 2003, ascertain and review the current priorities of the group, and devise a strategy for proceeding. The key accomplishments of GRAPPA to date, priorities and objectives for the next 5 years, and goals and opportunities for the GRAPPA committees were discussed. GRAPPA has a responsibility and commitment to patients, its members, and partners to innovate, inspire, and improve knowledge and the ability to care for people with psoriasis and psoriatic arthritis.

15 Article GRAPPA Trainees Symposium 2016: A Report from the GRAPPA 2016 Annual Meeting. 2017

Polachek, Ari / Stober, Carmel B / Gudbjornsson, Bjorn / Ritchlin, Christopher T. ·From the University of Toronto, Toronto, Ontario, Canada; University of Cambridge, Cambridge, UK; Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center, Rochester, New York, USA; Centre for Rheumatology Research, National University Hospital of Iceland, Reykjavik, Iceland. · A. Polachek, MD, Clinical and Research Fellow, University of Toronto; C.B. Stober, MBChB, PhD, University of Cambridge; B. Gudbjornsson, MD, PhD, Professor, Centre for Rheumatology Research, National University Hospital of Iceland; C.T. Ritchlin, MD, MPH, Professor of Medicine, Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center. · Dr. Polachek and Dr. Stober are joint first authors. · Department of Rheumatology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. · From the University of Toronto, Toronto, Ontario, Canada; University of Cambridge, Cambridge, UK; Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center, Rochester, New York, USA; Centre for Rheumatology Research, National University Hospital of Iceland, Reykjavik, Iceland. cbs24@medschl.cam.ac.uk. · A. Polachek, MD, Clinical and Research Fellow, University of Toronto; C.B. Stober, MBChB, PhD, University of Cambridge; B. Gudbjornsson, MD, PhD, Professor, Centre for Rheumatology Research, National University Hospital of Iceland; C.T. Ritchlin, MD, MPH, Professor of Medicine, Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center. cbs24@medschl.cam.ac.uk. · Dr. Polachek and Dr. Stober are joint first authors. cbs24@medschl.cam.ac.uk. ·J Rheumatol · Pubmed #28461521.

ABSTRACT: At the 2016 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) in Miami, Florida, USA, a trainees symposium was held. Rheumatology and dermatology trainees, engaged in psoriasis or psoriatic arthritis research, presented their work. This report briefly reviews 6 oral presentations and 21 posters presented at that meeting.

16 Article Dysfunctional Skin-Derived Glucocorticoid Synthesis Is a Pathogenic Mechanism of Psoriasis. 2017

Hannen, Rosalind / Udeh-Momoh, Chinedu / Upton, James / Wright, Michael / Michael, Anthony / Gulati, Abha / Rajpopat, Shefali / Clayton, Nicky / Halsall, David / Burrin, Jacky / Flower, Roderick / Sevilla, Lisa / Latorre, Victor / Frame, James / Lightman, Stafford / Perez, Paloma / Philpott, Michael. ·Centre for Cell Biology and Cutaneous Research, Institute of Cell and Molecular Science, Bart's and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. Electronic address: r.f.hannen@qmul.ac.uk. · Centre for Synaptic Plasticity, University of Bristol, Dorothy Hodgkin Building, Bristol, UK; Neuroepidemiology and Ageing Research Unit, Imperial Collage, London, UK. · Centre for Cell Biology and Cutaneous Research, Institute of Cell and Molecular Science, Bart's and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. · Department of Biochemistry, Addenbrookes Hospital, Cambridge, UK; LGC, Sport and Specialised Analytical Services, Fordham, Cambridgeshire, UK. · The School of Biological and Chemical Sciences, Queen Mary University of London, London, UK. · Department of Dermatology, The Royal London Hospital, Whitechapel, London, UK. · Department of Dermatology, Whipps Cross Hospital, Leytonstone, London, UK. · Department of Biochemistry, Addenbrookes Hospital, Cambridge, UK. · Centre for Endocrinology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. · Centre for Pharmacology and Biochemistry, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. · Instituto de Biomedicina de Valencia-Consejo Superior de Investigaciones Científicas, Valencia, Spain. · Anglia-Ruskin University, Chelmsford, Essex, UK. · Centre for Synaptic Plasticity, University of Bristol, Dorothy Hodgkin Building, Bristol, UK. ·J Invest Dermatol · Pubmed #28359725.

ABSTRACT: Glucocorticoids (GC) are the primary steroids that regulate inflammation and have been exploited therapeutically in inflammatory skin diseases. Despite the broad-spectrum therapeutic use of GC, the biochemical rationale for locally treating inflammatory skin conditions is poorly understood, as systemic GC production remains largely functional in these patients. GC synthesis has been well characterized in healthy skin, but the pathological consequence has not been examined. Here we show de novo GC synthesis, and GC receptor expression is dysfunctional in both nonlesional and lesional psoriatic skin. Use of GC receptor epidermal knockout mice with adrenalectomy allowed for the distinction between local (keratinocyte) and systemic GC activity. Compensation exhibited by adult GC receptor epidermal knockout mice demonstrated that keratinocyte-derived GC synthesis protected skin from topical phorbol 12-myristate 13-acetate-induced inflammatory assault. Thus, localized de novo GC synthesis in skin is essential for controlling inflammation, and loss of the GC pathway in psoriatic skin represents an additional pathological process in this complex inflammatory skin disease.

17 Article Axial Disease in Psoriatic Arthritis study: defining the clinical and radiographic phenotype of psoriatic spondyloarthritis. 2017

Jadon, Deepak R / Sengupta, Raj / Nightingale, Alison / Lindsay, Mark / Korendowych, Eleanor / Robinson, Graham / Jobling, Amelia / Shaddick, Gavin / Bi, Jing / Winchester, Robert / Giles, Jon T / McHugh, Neil J. ·Department of Rheumatology, Royal National Hospital for Rheumatic Diseases, Bath, UK. · Department of Rheumatology, Addenbrooke's Hospital, Cambridge, UK. · Department of Pharmacy & Pharmacology, University of Bath, Bath, UK. · Department of Mathematical Sciences, University of Bath, Bath, UK. · Columbia College of Physicians & Surgeons, New York, New York, USA. ·Ann Rheum Dis · Pubmed #27913376.

ABSTRACT: OBJECTIVES: To compare the prevalence, clinical and radiographic characteristics of psoriatic spondyloarthritis (PsSpA) in psoriatic arthritis (PsA), with ankylosing spondylitis (AS). METHODS: A prospective single-centre cross-sectional observational study recruited consecutive PsA and AS cases. Participants completed outcome measures, and underwent clinical examination, axial radiographic scoring and RESULTS: The 402 enrolled cases (201 PsA, 201 AS; fulfilling classification criteria for respective conditions) were reclassified based upon radiographic axial disease and psoriasis, as: 118 PsSpA, 127 peripheral-only PsA (pPsA), and 157 AS without psoriasis (AS) cases. A significant proportion of patients with radiographic axial disease had PsSpA (118/275; 42.91%), and often had symptomatically silent axial disease (30/118; 25.42%). Modified New York criteria for AS were fulfilled by 48/201 (23.88%) PsA cases, and Classification of Psoriatic Arthritis criteria by 49/201 (24.38%) AS cases. pPsA compared with PsSpA cases had a lower frequency of CONCLUSIONS: In a combined cohort of patients with either PsA or AS from a single centre, 24% fulfilled classification criteria for both conditions. The pattern of axial disease was influenced significantly by the presence of skin psoriasis and

18 Article Implications of the diversity of class I HLA associations in psoriatic arthritis. 2016

Winchester, Robert / Giles, Jon / Jadon, Deepak / Haroon, Muhammed / McHugh, Neil / FitzGerald, Oliver. ·Columbia University, College of Physicians and Surgeons, Division of Rheumatology, United States. Electronic address: rjw8@columbia.edu. · Columbia University, College of Physicians and Surgeons, Division of Rheumatology, United States. · Royal National Hospital for Rheumatic Diseases, Rheumatology Department, Bath, UK; Cambridge University Hospitals NHS Foundation Trust, Rheumatology Department, Department of Rheumatology, Addenbrooke's Hospital, Cambridge, UK. · Department of Rheumatology, St. Vincent's University Hospital and Conway Institute, University College Dublin, Dublin, Ireland; University Hospital Kerry, Kerry, Ireland. · Royal National Hospital for Rheumatic Diseases, Rheumatology Department, Bath, UK. · Department of Rheumatology, St. Vincent's University Hospital and Conway Institute, University College Dublin, Dublin, Ireland. ·Clin Immunol · Pubmed #27455857.

ABSTRACT: We sought to validate and extend the findings of a 282 psoriatic arthritis patient cohort from Dublin using a 219 patient cohort from Bath. The central finding of this study was that several structurally unrelated HLA alleles, including B*08:01:01, B*18:01:01, B*27:05:02, B*55:01:01 and C*06:02:01, were found to be significantly associated with particular phenotypic features of psoriatic arthritis, implying that the clinical diagnosis of psoriatic arthritis designates a genetically heterogeneous subset of individuals. Radiographic sacroiliitis was associated with either B*08:01:01, or B*27:05:02 with implications about the role of MHC molecules in an adaptive immune response. There are also implications for psoriatic arthritis diagnostic criteria since some disease features used in the criteria are under genetic control. These findings have important implications for understanding the role of MHC alleles in directing the adaptive immune response to mediate the inflammation responsible for psoriatic arthritis.

19 Article Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci. 2016

Ellinghaus, David / Jostins, Luke / Spain, Sarah L / Cortes, Adrian / Bethune, Jörn / Han, Buhm / Park, Yu Rang / Raychaudhuri, Soumya / Pouget, Jennie G / Hübenthal, Matthias / Folseraas, Trine / Wang, Yunpeng / Esko, Tonu / Metspalu, Andres / Westra, Harm-Jan / Franke, Lude / Pers, Tune H / Weersma, Rinse K / Collij, Valerie / D'Amato, Mauro / Halfvarson, Jonas / Jensen, Anders Boeck / Lieb, Wolfgang / Degenhardt, Franziska / Forstner, Andreas J / Hofmann, Andrea / Anonymous3910861 / Anonymous3920861 / Anonymous3930861 / Anonymous3940861 / Anonymous3950861 / Schreiber, Stefan / Mrowietz, Ulrich / Juran, Brian D / Lazaridis, Konstantinos N / Brunak, Søren / Dale, Anders M / Trembath, Richard C / Weidinger, Stephan / Weichenthal, Michael / Ellinghaus, Eva / Elder, James T / Barker, Jonathan N W N / Andreassen, Ole A / McGovern, Dermot P / Karlsen, Tom H / Barrett, Jeffrey C / Parkes, Miles / Brown, Matthew A / Franke, Andre. ·Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany. · Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK. · Nuffield Department of Clinical Neurosciences, Division of Clinical Neurology, John Radcliffe Hospital, University of Oxford, Oxford, UK. · Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. · Department of Convergence Medicine, University of Ulsan College of Medicine and Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea. · Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea. · Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. · Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts, USA. · Division of Rheumatology, Brigham and Women's Hospital, Boston, Massachusetts, USA. · Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA. · Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. · Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. · Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway. · K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. · Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway. · Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway. · Department of Neurosciences, University of California, San Diego, La Jolla, California, USA. · Estonian Genome Center, University of Tartu, Tartu, Estonia. · Division of Endocrinology, Boston Children's Hospital, Cambridge, Massachusetts, USA. · Center for Basic and Translational Obesity Research, Boston Children's Hospital, Cambridge, Massachusetts, USA. · University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands. · Novo Nordisk Foundation Centre for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark. · Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. · Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands. · Department of Bioscience and Nutrition, Karolinska Institutet, Stockholm, Sweden. · BioCruces Health Research Institute and Ikerbasque, Basque Foundation for Science, Bilbao, Spain. · Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden. · Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. · Institute of Epidemiology, University Hospital Schleswig-Holstein, Kiel, Germany. · PopGen Biobank, University Hospital Schleswig-Holstein, Kiel, Germany. · Institute of Human Genetics, University of Bonn, Bonn, Germany. · Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany. · Department of General Internal Medicine, Universitätsklinikum Schleswig-Holstein Campus Kiel, Kiel, Germany. · Department of Dermatology, University Hospital, Schleswig-Holstein, Christian Albrechts University of Kiel, Kiel, Germany. · Center for Basic Research in Digestive Diseases, Division of Gastroenterology and Hepatology, Mayo Clinic, College of Medicine, Rochester, Minnesota, USA. · Department of Radiology, University of California, San Diego, La Jolla, California, USA. · Division of Genetics and Molecular Medicine, King's College London, London, UK. · Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA. · Ann Arbor Veterans Affairs Hospital, Ann Arbor, Michigan, USA. · St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, King's College London, London, UK. · NORMENT, K.G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. · Division of Mental Health and Addiction, Oslo University Hospital, Ullevål, Oslo, Norway. · F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Los Angeles, California, USA. · Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA. · Inflammatory Bowel Disease Research Group, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK. · University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia. · Institute of Health and Biomedical Innovation (IHBI), Faculty of Health, Queensland University of Technology (QUT), Translational Research Institute, Brisbane, Queensland, Australia. ·Nat Genet · Pubmed #26974007.

ABSTRACT: We simultaneously investigated the genetic landscape of ankylosing spondylitis, Crohn's disease, psoriasis, primary sclerosing cholangitis and ulcerative colitis to investigate pleiotropy and the relationship between these clinically related diseases. Using high-density genotype data from more than 86,000 individuals of European ancestry, we identified 244 independent multidisease signals, including 27 new genome-wide significant susceptibility loci and 3 unreported shared risk loci. Complex pleiotropy was supported when contrasting multidisease signals with expression data sets from human, rat and mouse together with epigenetic and expressed enhancer profiles. The comorbidities among the five immune diseases were best explained by biological pleiotropy rather than heterogeneity (a subgroup of cases genetically identical to those with another disease, possibly owing to diagnostic misclassification, molecular subtypes or excessive comorbidity). In particular, the strong comorbidity between primary sclerosing cholangitis and inflammatory bowel disease is likely the result of a unique disease, which is genetically distinct from classical inflammatory bowel disease phenotypes.

20 Article Late cornified envelope (LCE) proteins: distinct expression patterns of LCE2 and LCE3 members suggest nonredundant roles in human epidermis and other epithelia. 2016

Niehues, H / van Vlijmen-Willems, I M J J / Bergboer, J G M / Kersten, F F J / Narita, M / Hendriks, W J A J / van den Bogaard, E H / Zeeuwen, P L J M / Schalkwijk, J. ·Department of Dermatology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, PO Box 9101, 6500 HB, Nijmegen, the Netherlands. · Massachusetts General Hospital/Harvard Medical School, Boston, MA, U.S.A. · Cancer Research U.K. Cambridge Institute, University of Cambridge, The Li Ka Shing Centre, Cambridge, U.K. · Department of Cell Biology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, PO Box 9101, 6500 HB, Nijmegen, the Netherlands. ·Br J Dermatol · Pubmed #26556599.

ABSTRACT: BACKGROUND: Deletion of the late cornified envelope (LCE) proteins LCE3B and LCE3C is a strong and widely replicated psoriasis risk factor. It is amenable to biological analysis because it precludes the expression of two epidermis-specific proteins, rather than being a single-nucleotide polymorphism of uncertain significance. The biology of the 18-member LCE family of highly homologous proteins has remained largely unexplored so far. OBJECTIVES: To analyse LCE3 expression at the protein level in human epithelia, as a starting point for functional analyses of these proteins in health and disease. METHODS: We generated the first pan-LCE3 monoclonal antibody and provide a detailed analysis of its specificity towards individual LCE members. LCE2 and LCE3 expression in human tissues and in reconstructed human skin models was studied using immunohistochemical analyses and quantitative polymerase chain reaction. RESULTS: Our study reveals that LCE2 and LCE3 proteins are differentially expressed in human epidermis, and colocalize only in the upper stratum granulosum layer. Using an in vitro reconstructed human skin model that mimics epidermal morphogenesis, we found that LCE3 proteins are expressed at an early time point during epidermal differentiation in the suprabasal layers, while LCE2 proteins are found only in the uppermost granular layer and stratum corneum. CONCLUSIONS: Based on the localization of LCE2 and LCE3 in human epidermis we conclude that members of the LCE protein family are likely to have distinct functions in epidermal biology. This finding may contribute to understanding why LCE3B/C deletion increases psoriasis risk.

21 Article A corrected formulation for marginal inference derived from two-part mixed models for longitudinal semi-continuous data. 2016

Tom, Brian Dm / Su, Li / Farewell, Vernon T. ·Medical Research Council Biostatistics Unit, Institute of Public Health, Cambridge, UK brian.tom@mrc-bsu.cam.ac.uk. · Medical Research Council Biostatistics Unit, Institute of Public Health, Cambridge, UK. ·Stat Methods Med Res · Pubmed #24201470.

ABSTRACT: For semi-continuous data which are a mixture of true zeros and continuously distributed positive values, the use of two-part mixed models provides a convenient modelling framework. However, deriving population-averaged (marginal) effects from such models is not always straightforward. Su et al. presented a model that provided convenient estimation of marginal effects for the logistic component of the two-part model but the specification of marginal effects for the continuous part of the model presented in that paper was based on an incorrect formulation. We present a corrected formulation and additionally explore the use of the two-part model for inferences on the overall marginal mean, which may be of more practical relevance in our application and more generally.

22 Article Biologic therapy for inflammatory arthritis and latent tuberculosis: real world experience from a high prevalence area in the United Kingdom. 2015

Nisar, Muhammad K / Rafiq, Aneesa / Östör, Andrew J K. ·Rheumatology Department, Luton & Dunstable University Hospital NHSFT, Lewsey Road, Luton, LU4 0DZ, UK. drnisar12@yahoo.co.uk. · Rheumatology Department, Luton & Dunstable University Hospital NHSFT, Lewsey Road, Luton, LU4 0DZ, UK. · Rheumatology Research Unit, Addenbrooke's Hospital, Cambridge, UK. ·Clin Rheumatol · Pubmed #26497501.

ABSTRACT: Biologic therapies have resulted in a sea change in the management of inflammatory arthritis; however, a higher risk of opportunistic infection, particularly tuberculosis (TB), is well recognised. This has led to the development of TB screening guidelines. The aim of this study was to investigate the prevalence of latent TB in patients prescribed biologic therapy in an endemic area (prevalence of TB 50/100,000) and to assess the risk of subsequent reactivation. Retrospective case note review of all patients with inflammatory arthritis ever prescribed biologic therapy between 1998 and 2014 at our centre. Two hundred ninety-nine patients (109 men, 190 women) who had ever been prescribed biologic therapy over a 16-year period were included. Mean age upon commencing the biologic therapy was 51 years. Two hundred eighteen (73 %) patients were Caucasian with remaining from ethnic minorities. Two hundred thirty-nine (80 %) prescriptions were for TNF inhibitors. Median duration of biologic therapy was 4.2 years for those who remained on treatment prior to stopping or switching therapies. During 1998-2007, 112 patients underwent clinical assessment, chest X-ray and check for BCG scar. One patient of Asian origin developed extrapulmonary TB within 6 weeks of adalimumab initiation. Following a year of anti-TB treatment, he restarted the biologic therapy with no ill effects. One hundred eighty-seven participants (who started on biologic therapy between 2008 and 2014) underwent additional interferon gamma release assays (IGRA) testing as part of a new TB screening protocol (T-spot test). Eighteen (10 %) had positive test with normal chest X-rays. Six patients were white, nine of Asian origin and three others. Three Caucasian patients had a borderline result. All had 3 months of isoniazid and rifampicin with simultaneous prescription of biologic agent (13 had TNF antagonist, 5 rituximab and 3 tocilizumab). No cases of active TB infection were observed. Overall prevalence of latent TB in patients with inflammatory arthritis prescribed biologic therapy in an endemic area is 10 %. The risk warrants careful screening and monitoring in all patients. Adherence to strict screening protocol reduces the risk of active TB infection irrespective of the biologic therapy employed.

23 Article The Budget Impact of Biosimilar Infliximab (Remsima®) for the Treatment of Autoimmune Diseases in Five European Countries. 2015

Jha, Ashok / Upton, Alex / Dunlop, William C N / Akehurst, Ron. ·Mundipharma International Ltd., Cambridge, UK. · Abacus International, Bicester, UK. · Mundipharma International Ltd., Cambridge, UK. will.dunlop@mundipharma.co.uk. · School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK. · BresMed Health Solutions Limited, Northchurch Business Centre, Sheffield, UK. ·Adv Ther · Pubmed #26343027.

ABSTRACT: INTRODUCTION: Inflammatory autoimmune diseases (rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriasis, and psoriatic arthritis) have a considerable impact on patients' quality of life and healthcare budgets. Biosimilar infliximab (Remsima(®)) has been authorized by the European Medicines Agency for the management of inflammatory autoimmune diseases based on a data package demonstrating efficacy, safety, and quality comparable to the reference infliximab product (Remicade(®)). This analysis aims to estimate the 1-year budget impact of the introduction of Remsima in five European countries. METHODS: A budget impact model for the introduction of Remsima in Germany, the UK, Italy, the Netherlands, and Belgium was developed over a 1-year time horizon. Infliximab-naïve and switch patient groups were considered. Only direct drug costs were included. The model used the drug-acquisition cost of Remicade. The list price of Remsima was not known at the time of the analysis, and was assumed to be 10-30% less than that of Remicade. Key variables were tested in the sensitivity analysis. RESULTS: The annual cost savings resulting from the introduction of Remsima were projected to range from €2.89 million (Belgium, 10% discount) to €33.80 million (Germany, 30% discount). If any such savings made were used to treat additional patients with Remsima, 250 (Belgium, 10% discount) to 2602 (Germany, 30% discount) additional patients could be treated. The cumulative cost savings across the five included countries and the six licensed disease areas were projected to range from €25.79 million (10% discount) to €77.37 million (30% discount). Sensitivity analyses showed the number of patients treated with infliximab to be directly correlated with projected cost savings, with disease prevalence and patient weight having a smaller impact, and incidence the least impact. CONCLUSION: The introduction of Remsima could lead to considerable drug cost-related savings across the six licensed disease areas in the five European countries. FUNDING: Mundipharma International Ltd.

24 Article Intra-articular etanercept treatment in inflammatory arthritis: A randomized double-blind placebo-controlled proof of mechanism clinical trial validating TNF as a potential therapeutic target for local treatment. 2015

Aalbers, Caroline / Gerlag, Danielle / Vos, Koen / Vervoordeldonk, Margriet / Landewé, Robert / Tak, Paul Peter. ·Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; Arthrogen B.V., Meibergdreef 45, 1105 BA Amsterdam, The Netherlands. Electronic address: c.j.aalbers@amc.uva.nl. · Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. · Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; Department of rheumatology, Flevoziekenhuis, Hospitaalweg 1, 1315 RA Almere, The Netherlands. · Arthrogen B.V., Meibergdreef 45, 1105 BA Amsterdam, The Netherlands. · Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; Department of Rheumatology, Atrium Medical Center, Postbus 4446, 6401 CX Heerlen, The Netherlands. · Arthrogen B.V., Meibergdreef 45, 1105 BA Amsterdam, The Netherlands; GlaxoSmithKline, Stevenage, UK; University of Cambridge, Cambridge, UK; Ghent University, Ghent, Belgium. ·Joint Bone Spine · Pubmed #26188879.

ABSTRACT: OBJECTIVE: There is an increased interest in developing gene therapy approaches for local delivery of therapeutic genes in patients with arthritis. Intra-articular (i.a.) gene delivery, using an adeno-associated virus encoding a TNF soluble receptor, resulted in reduced paw swelling in an arthritis animal model, but i.a. treatment with a similar vector did not induce robust clinical improvement in patients. It is unclear whether this can be explained by for instance insufficient transduction efficiency or the fact that TNF is not a good therapeutic target for i.a treatment. The objective of this study was to explore the effects of i.a TNF blockade. METHODS: Thirty-one patients with rheumatoid or psoriatic arthritis were assigned to a single i.a. injection of 25mg etanercept or placebo in a double-blind randomised controlled clinical trial. The primary end point was target joint improvement, determined by a composite change index. RESULTS: Twenty-two patients received etanercept and 9 received placebo. Treatment was generally well tolerated. Treatment with etanercept resulted in a prompt and statistically significant improvement of the index (P<0.001) in comparison with placebo. As expected in light of the half-life of etanercept, the beneficial effect was transient and only statistically significant at week 1 and 2 after i.a. injection. CONCLUSION: The results support the development of novel approaches for long-term inhibition of TNF at the site of inflammation, such as gene therapy. TRIAL REGISTRATION: The Netherlands National Trial Register (NTR), www.trialregister.nl, NTR-1210.

25 Article Single-joint Assessment for the Evaluation of Intraarticular Treatment: Responsiveness and Discrimination of the Composite Change Index. 2015

Aalbers, Caroline J / Gerlag, Danielle M / Vervoordeldonk, Margriet J / Tak, Paul P / Landewé, Robert B. ·From the Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam; Arthrogen B.V., Amsterdam; Department of Rheumatology, Atrium Medical Center, Heerlen, the Netherlands.C.J. Aalbers, MD, Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, and Arthrogen B.V.; D.M. Gerlag, MD, PhD, Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam; M.J. Vervoordeldonk, PhD, Arthrogen B.V.; P.P. Tak, MD, PhD, Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, and Arthrogen B.V., and GlaxoSmithKline, and University of Cambridge; R.B. Landewé, MD, PhD, Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, and Department of Rheumatology, Atrium Medical Center. ·J Rheumatol · Pubmed #26178282.

ABSTRACT: OBJECTIVE: To investigate responsiveness, discrimination, and construct validity of a composite change index (CCI) for the assessment of single-joint involvement in inflammatory arthritis. METHODS: Evaluation of standardized response means (SRM), Guyatt effect size, and Spearman rank correlation coefficient in a randomized controlled trial investigating the effect of an intraarticular etanercept injection. RESULTS: The CCI showed a high SRM (1.68) and high Guyatt effect size (2.72). Both visual analog scale of pain and functionality had a moderate Guyatt effect size (2.06, 2.44) and high SRM (0.81, 0.97). CONCLUSION: This study supports the use of the CCI as a single-joint assessment after single-joint intervention. CLINICAL TRIAL REGISTRATION: NTR-1210.

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