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Psoriasis: HELP
Articles from Guy's and St Thomas' NHS Trust
Based on 71 articles published since 2008
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These are the 71 published articles about Psoriasis that originated from Guy's and St Thomas' NHS Trust during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Guideline European S3-Guideline on the systemic treatment of psoriasis vulgaris - Update Apremilast and Secukinumab - EDF in cooperation with EADV and IPC. 2017

Nast, A / Spuls, P I / van der Kraaij, G / Gisondi, P / Paul, C / Ormerod, A D / Saiag, P / Smith, C H / Dauden, E / de Jong, E M / Feist, E / Jobling, R / Maccarone, M / Mrowietz, U / Papp, K A / Reich, K / Rosumeck, S / Talme, T / Thio, H B / van de Kerkhof, P / Werner, R N / Dressler, C. ·Division of Evidence-Based Medicine, Department of Dermatology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. · Department of Dermatology, Academic Medical Center, Amsterdam, The Netherlands. · Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy. · Department of Dermatology, Paul Sabatier University, Toulouse, France. · Department of Dermatology, Aberdeen Royal Infirmary, Aberdeen, UK. · Service de Dermatologie, Hôpital Ambroise Paré Université Paris V, Boulogne, France. · St Johns Institute of Dermatology, Guys and St Thomas' Hospital Foundation Trust, London, UK. · Hospital Universitario de la Princesa, Madrid, Spain. · Radboud University medical center and Radboud University, Nijmegen, The Netherlands. · Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany. · Cambridge, UK. · Roma, Italy. · Department of Dermatology, Psoriasis-Center University Medical Center Schleswig Holstein, Kiel, Germany. · Waterloo, Canada. · Dermatologikum Hamburg, Hamburg, Germany. · Section of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden. ·J Eur Acad Dermatol Venereol · Pubmed #28895202.

ABSTRACT: -- No abstract --

2 Guideline British Association of Dermatologists guidelines for biologic therapy for psoriasis 2017. 2017

Smith, C H / Jabbar-Lopez, Z K / Yiu, Z Z / Bale, T / Burden, A D / Coates, L C / Cruickshank, M / Hadoke, T / MacMahon, E / Murphy, R / Nelson-Piercy, C / Owen, C M / Parslew, R / Peleva, E / Pottinger, E / Samarasekera, E J / Stoddart, J / Strudwicke, C / Venning, V A / Warren, R B / Exton, L S / Mohd Mustapa, M F. ·St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, SE1 9RT, U.K. · The Dermatology Centre, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, Manchester, M13 9NT, U.K. · British Dermatology Nursing Group representative, Aneurin Bevan Health Board, Wales, U.K. · Department of Dermatology, Royal Infirmary of Edinburgh, Edinburgh, EH3 9HA, U.K. · British Society for Rheumatology, Chapel Allerton Hospital, Leeds, LS7 4SA, U.K. · Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, OX3 7LD, U.K. · National Guideline Centre, Royal College of Physicians, London, NW1 4LE, U.K. · Patient representatives. · Department of Infectious Diseases, Guy's and St Thomas' NHS Foundation Trust, London, SE1 9RT, U.K. · Department of Dermatology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, S10 2JF, U.K. · Women's Health Academic Centre, Guy's and St Thomas' NHS Foundation Trust, London, SE1 9RT, U.K. · Department of Dermatology, East Lancashire Hospitals NHS Trust, Burnley, BB10 2PQ, U.K. · Department of Dermatology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, L7 8XP, U.K. · Independent chair, Healthcare Quality Improvement Partnership, London, EC2Y 9AE, U.K. · Department of Dermatology, Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 7LE, U.K. · British Association of Dermatologists, London, W1T 5HQ, U.K. ·Br J Dermatol · Pubmed #28513835.

ABSTRACT: -- No abstract --

3 Guideline European S3-Guidelines on the systemic treatment of psoriasis vulgaris--Update 2015--Short version--EDF in cooperation with EADV and IPC. 2015

Nast, A / Gisondi, P / Ormerod, A D / Saiag, P / Smith, C / Spuls, P I / Arenberger, P / Bachelez, H / Barker, J / Dauden, E / de Jong, E M / Feist, E / Jacobs, A / Jobling, R / Kemény, L / Maccarone, M / Mrowietz, U / Papp, K A / Paul, C / Reich, K / Rosumeck, S / Talme, T / Thio, H B / van de Kerkhof, P / Werner, R N / Yawalkar, N. ·Division of Evidence Based Medicine, Department of Dermatology, Charité - Universitätsmedizin Berlin, Berlin, Germany. · Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy. · Department of Dermatology, Aberdeen Royal Infirmary, Aberdeen, UK. · Service de Dermatologie, Hôpital Ambroise Paré Université Paris V, Boulogne, France. · Clinical Lead for Dermatology, St Johns Institute of Dermatology, St Thomas' Hospital, London, UK. · Department of Dermatology, Academic Medical Center, Amsterdam, The Netherlands. · Third Faculty of Medicine, Department of Dermatology, Charles University, Prague, Czech Republic. · Department of Dermatology, Hôpital Saint-Louis, Paris, France. · St. Johns Institute of Dermatology, St. Thomas' Hospital, London, UK. · Hospital Universitario de la Princesa, Madrid, Spain. · University Medical Center Nijmegen St Radboud, Nijmegen, The Netherlands. · Medizinische Klinik mit Schwerpunkt Rheumatologie u. klinische Immonologie, Charité - Universitätsmedizin Berlin, Berlin, Germany. · Cambridge, UK. · SZTE Borgyogyaszati Klinika, Szeged, Hungary. · Roma, Italy. · Department of Dermatology, Psoriasis-Center University Medical Center Schleswig Holstein, Kiel, Germany. · Waterloo, Canada. · Department of Dermatology, Paul Sabatier University, Toulouse, France. · Dermatologikum Hamburg, Hamburg, Germany. · Section of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden. · Department of Dermatology, Erasmus University, Rotterdam, The Netherlands. · Department of Dermatology, University Hospital Nijmegen, Nijmegen, The Netherlands. · Department of Dermatology, Inselspital, Universitätsklinik für Dermatologie, Bern, Switzerland. ·J Eur Acad Dermatol Venereol · Pubmed #26481193.

ABSTRACT: -- No abstract --

4 Guideline British Association of Dermatologists' guidelines for biologic interventions for psoriasis 2009. 2009

Smith, C H / Anstey, A V / Barker, J N W N / Burden, A D / Chalmers, R J G / Chandler, D A / Finlay, A Y / Griffiths, C E M / Jackson, K / McHugh, N J / McKenna, K E / Reynolds, N J / Ormerod, A D / Anonymous3180641. ·St John's Institute of Dermatology, King's College London and Guy's and St Thomas' NHS Foundation Trust, London, UK. catherine.smith@kcl.ac.uk ·Br J Dermatol · Pubmed #19857207.

ABSTRACT: -- No abstract --

5 Editorial Biologics for psoriasis: more drugs, new patient categories, but fresh challenges for clinical dermatologists. 2017

Pink, A E / Smith, C H. ·St. John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, U.K. ·Br J Dermatol · Pubmed #28731243.

ABSTRACT: -- No abstract --

6 Editorial Psoriasis heritability: 125 years and counting. 2014

Barker, J. ·St John's Institute of Dermatology, King's College London, Guy's Hospital Campus, 9th Floor, Tower Wing, London, SE1 9RT, U.K.. jonathan.barker@kcl.ac.uk. ·Br J Dermatol · Pubmed #25066284.

ABSTRACT: -- No abstract --

7 Review Quantitative Evaluation of Biologic Therapy Options for Psoriasis: A Systematic Review and Network Meta-Analysis. 2017

Jabbar-Lopez, Zarif K / Yiu, Zenas Z N / Ward, Victoria / Exton, Lesley S / Mohd Mustapa, M Firouz / Samarasekera, Eleanor / Burden, A David / Murphy, Ruth / Owen, Caroline M / Parslew, Richard / Venning, Vanessa / Warren, Richard B / Smith, Catherine H. ·Unit for Population-Based Dermatology Research, St John's Institute of Dermatology, King's College London and Guy's and St Thomas' NHS Foundation Trust, London, UK. · Dermatology Centre, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. · University College London Hospital, London, UK. · British Association of Dermatologists, London, UK. · National Guideline Centre, Royal College of Physicians, London, UK. · Department of Dermatology, Royal Infirmary of Edinburgh, Edinburgh, UK. · Sheffield University Teaching Hospitals and Sheffield Children's Hospitals, Sheffield, UK. · Department of Dermatology, East Lancashire Hospitals NHS Trust, Royal Blackburn Hospital, Blackburn, UK. · Department of Dermatology, Royal Liverpool and Broadgreen University Hospitals Trust, Liverpool, UK. · Department of Dermatology, Oxford University Hospitals Foundation Trust, Oxford, UK. · St John's Institute of Dermatology, Guy's and St. Thomas' NHS Foundation Trust, London, UK. Electronic address: catherine.smith@kcl.ac.uk. ·J Invest Dermatol · Pubmed #28457908.

ABSTRACT: Multiple biologic treatments are licensed for psoriasis. The lack of head-to-head randomized controlled trials makes choosing between them difficult for patients, clinicians, and guideline developers. To establish their relative efficacy and tolerability, we searched MEDLINE, PubMed, Embase, and Cochrane for randomized controlled trials of licensed biologic treatments for skin psoriasis. We performed a network meta-analysis to identify direct and indirect evidence comparing biologics with one another, methotrexate, or placebo. We combined this with hierarchical cluster analysis to consider multiple outcomes related to efficacy and tolerability in combination for each treatment. Study quality, heterogeneity, and inconsistency were evaluated. Direct comparisons from 41 randomized controlled trials (20,561 participants) were included. All included biologics were efficacious compared with placebo or methotrexate at 3-4 months. Overall, cluster analysis showed adalimumab, secukinumab, and ustekinumab were comparable in terms of high efficacy and tolerability. Ixekizumab and infliximab were differentiated by very high efficacy but poorer tolerability. The lack of longer term controlled data limited our analysis to short-term outcomes. Trial performance may not equate to real-world performance, and so results need to be considered alongside real-world, long-term safety and effectiveness data. These data suggest that it is possible to discriminate between biologics to inform clinical practice and decision making (PROSPERO 2015:CRD42015017538).

8 Review Psoriatic arthritis. 2016

Durham, L E / Taams, L S / Kirkham, B W. ·Clinical Training Fellow. Centre for Molecular and Cellular Biology of Inflammation, Division of Immunology, Infection and Inflammatory Disease, King's College London, London. · Professor in Immunobiology and head of the Centre for Molecular and Cellular Biology of Inflammation, Division of Immunology, Infection and Inflammatory Disease, King's College London, London. · Consultant Rheumatologist in the Department of Rheumatology, Guy's & St Thomas' NHS Foundation Trust, London SE1 9RT. ·Br J Hosp Med (Lond) · Pubmed #27388392.

ABSTRACT: -- No abstract --

9 Review Risk of Serious Infections in Patients with Psoriasis on Biologic Therapies: A Systematic Review and Meta-Analysis. 2016

Yiu, Zenas Z N / Exton, Lesley S / Jabbar-Lopez, Zarif / Mohd Mustapa, M Firouz / Samarasekera, Eleanor J / Burden, A David / Murphy, Ruth / Owen, Caroline M / Parslew, Richard / Venning, Vanessa / Ashcroft, Darren M / Griffiths, Christopher E M / Smith, Catherine H / Warren, Richard B. ·Dermatology Centre, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK; Centre for Pharmacoepidemiology and Drug Safety, Manchester Pharmacy School, The University of Manchester, Manchester, UK. · British Association of Dermatologists, London, UK. · Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK. · National Clinical Guideline Centre, Royal College of Physicians of London, London, UK. · Department of Dermatology, Western Infirmary, Glasgow, UK. · Sheffield University Teaching Hospitals and Sheffield Children's Hospitals, Sheffield, UK. · Department of Dermatology, East Lancashire Hospitals NHS Trust, Royal Blackburn Hospital, Blackburn, Lancashire, UK. · Department of Dermatology, Royal Liverpool and Broadgreen University Hospitals Trust, Liverpool, UK. · Department of Dermatology, Oxford University Hospitals Foundation Trust, Oxford, UK. · Centre for Pharmacoepidemiology and Drug Safety, Manchester Pharmacy School, The University of Manchester, Manchester, UK. · Dermatology Centre, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. · St John's Institute of Dermatology, Guy's and St. Thomas' NHS Foundation Trust, London, UK. Electronic address: catherine.smith@kcl.ac.uk. · Dermatology Centre, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. Electronic address: richard.warren@manchester.ac.uk. ·J Invest Dermatol · Pubmed #27085754.

ABSTRACT: A comprehensive evaluation of the risk of serious infections in biologic therapies for psoriasis is lacking. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) and prospective cohort studies reporting serious infections in people taking any licensed biologic therapy for psoriasis compared with those taking placebo, nonbiologic therapy, or other biologic therapies. The quality of the studies was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria. No significant heterogeneity was detected in data from 32 RCTs (n = 13,359 participants) and one cohort study (n = 4,993 participants). In adults, low- to very-low-quality RCT data showed no significant difference between any biologic therapy and placebo at weeks 12-16 (overall pooled Peto odds ratio = 0.71, 95% confidence interval = 0.36-1.41) and weeks 20-30 (odds ratio = 2.27, 95% confidence interval = 0.45-11.49). No significant differences were found in any of the other comparisons in underpowered RCT data. Prospective cohort study data of low quality suggests that only adalimumab (adjusted hazard ratio [adjHR] = 2.52, 95% confidence interval = 1.47-4.32) was associated with a significantly higher risk of serious infection compared with retinoid and/or phototherapy in adults. No association between biologic therapies and serious infections in patients with psoriasis who were eligible for RCTs was detected. Further observational studies are needed to inform the uncertainty around this risk in the real world.

10 Review A Review on the Potential Role of Basement Membrane Laminin in the Pathogenesis of Psoriasis. 2016

McFadden, J P / Kimber, I. ·Department of Cutaneous Allergy, St John's Institute of Dermatology, Kings College, Guy's Hospital, London, UK. · Faculty of Life Sciences, University of Manchester, Manchester, UK. ·Scand J Immunol · Pubmed #26346598.

ABSTRACT: We have previously reviewed alterations to basement membrane laminin in psoriasis and how disruption of this layer could lead to at least some of the pathological changes observed. We here postulate that basement membrane laminin is the key antigen in driving psoriasis, inducing a T cell-mediated autoimmune response. For laminin to be considered as the key autoantigen in psoriasis, it would be reasonable to expect the following to be demonstrable: (1) that autoantigens are present in psoriatic inflammation; (2) that basement membrane laminin is perturbed in involved and uninvolved skin, and that some of the pathological changes associated with psoriasis could be predicted as a sequel to this; (3) that disruption of the basement membrane is among the earliest events in the evolution of psoriatic lesions; (4) that as streptococcal pharyngitis is the most clearly defined event to trigger or exacerbate psoriasis, then a T cell-mediated autoimmune response to laminin should be anticipated as a potential sequelae to streptococcal pharyngitis; (5) that T cells in psoriasis can be shown to react to peptides with homology to laminin; (6) that HLACw6, as the most closely related gene associated with psoriasis and which is involved in antigen expression, should be preferentially expressed within lesional psoriasis towards the basement membrane, together with other proximal associated immune activity; and (7) that there is some association between antilaminin pemphigoid, a humorally mediated autoimmune disease to skin basement membrane laminin, and psoriasis. We here review the data relevant to each of these requirements.

11 Review Pathogenesis and treatment of psoriasis: exploiting pathophysiological pathways for precision medicine. 2015

Alwan, Wisam / Nestle, Frank O. ·St. John's Institute of Dermatology, Guy's and St. Thomas' Hospitals NHS Foundation Trust, London, UK. · St. John's Institute of Dermatology, Guy's and St. Thomas' Hospitals NHS Foundation Trust, London, UK. frank.nestle@kcl.ac.uk. ·Clin Exp Rheumatol · Pubmed #26472336.

ABSTRACT: Psoriasis is a common, chronic inflammatory skin disease associated with multi-system manifestations including arthritis and obesity. Our knowledge of the aetiology of the condition, including the key genomic, immune and environmental factors, has led to the development of targeted, precision therapies that alleviate patient morbidity. This article reviews the key pathophysiological pathways and therapeutic targets and highlights future areas of interest in psoriasis research.

12 Review Genetics of psoriasis. 2015

Mahil, Satveer K / Capon, Francesca / Barker, Jonathan N. ·Division of Genetics and Molecular Medicine, St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, King's College London, 9th Floor, Tower Wing, London SE1 9RT, UK. · Division of Genetics and Molecular Medicine, King's College London, Guy's Hospital, 9th Floor, Tower Wing, London, SE1 9RT, UK. · Division of Genetics and Molecular Medicine, St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, King's College London, 9th Floor, Tower Wing, London SE1 9RT, UK. Electronic address: jonathan.barker@kcl.ac.uk. ·Dermatol Clin · Pubmed #25412779.

ABSTRACT: Psoriasis is a common and debilitating immune-mediated skin disease with a complex genetic basis. Genetic studies have provided critical insights into the pathogenesis of disease. This article focuses on the results of genetic association studies, which provide evidence that psoriasis susceptibility genes are involved in innate and adaptive immunity and skin barrier functions. The potential for disease stratification and the development of more effective treatments with fewer side effects using genetic data are highlighted.

13 Review The IL-23/IL-17 axis in psoriatic arthritis. 2014

Suzuki, Erika / Mellins, Elizabeth D / Gershwin, M Eric / Nestle, Frank O / Adamopoulos, Iannis E. ·Department of Internal Medicine, Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA 95616, USA. · Divisions of Human Gene Therapy and Pediatric Rheumatology, Program in Immunology, Stanford University, Palo Alto, CA 94305, USA. · St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital, London, United Kingdom. · Department of Internal Medicine, Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA 95616, USA; Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, CA 95817, USA. Electronic address: iannis@ucdavis.edu. ·Autoimmun Rev · Pubmed #24424175.

ABSTRACT: Psoriatic arthritis (PsA) is an immune-mediated chronic inflammatory disease, affecting both the skin and joints. Disease progression is associated with aberrant cytokine expression, and TNF blockade is the most successful therapy to date. However, not all patients are responsive to anti-TNF treatment, highlighting the need to better understand the cellular and molecular mechanisms that govern the disease. PsA associations with single nucleotide polymorphisms in IL23R as well as TRAF3IP2 (Act1), a molecule downstream of the IL-17 receptor (IL-17R), have linked the IL-23/IL-17 axis to disease pathology. Although both cytokines are implicated in PsA, a full picture of their cellular targets and pathogenic mechanisms has not yet emerged. In this review, we focus on the IL-23/IL-17 axis-elicited responses mediated by osteoclasts, keratinocytes and neutrophils. Expanding our understanding of the cellular and molecular mechanisms that dictate pathogenicity in PsA will contribute to developing novel treatment strategies to combat disease.

14 Review Interleukin-17A: a unique pathway in immune-mediated diseases: psoriasis, psoriatic arthritis and rheumatoid arthritis. 2014

Kirkham, Bruce W / Kavanaugh, Arthur / Reich, Kristian. ·Department of Rheumatology, Guy's & St Thomas' NHS Foundation Trust, London, UK. ·Immunology · Pubmed #23819583.

ABSTRACT: Experimental evidence points to the importance of the cytokine interleukin-17A (IL-17A) in the pathogenesis of several immunoinflammatory diseases including psoriasis, psoriatic arthritis and rheumatoid arthritis. Although a principal effector of T helper type 17 cells, IL-17A is produced by many other cell types including CD8(+) T cells and γδ T cells, and is found at high levels associated with mast cells and neutrophils at sites of skin and joint disease in humans. IL-17A up-regulates expression of numerous inflammation-related genes in target cells such as keratinocytes and fibroblasts, leading to increased production of chemokines, cytokines, antimicrobial peptides and other mediators that contribute to clinical disease features. Importantly, IL-17A must be considered within the context of the local microenvironment, because it acts synergistically or additively with other pro-inflammatory cytokines, including tumour necrosis factor. Several direct IL-17A inhibitors have shown promising activity in proof of concept and phase 2 clinical studies, thereby providing confirmation of experimental data supporting IL-17A in disease pathogenesis, although levels of response are not predicted by pre-clinical findings. IL-17A inhibitors produced rapid down-regulation of the psoriasis gene signature and high clinical response rates in patients with moderate-to-severe plaque psoriasis, consistent with an important role for IL-17A in psoriasis pathogenesis. Clinical response rates with IL-17A inhibitors in psoriatic arthritis and rheumatoid arthritis, however, were improved to a lesser degree compared with placebo, suggesting that IL-17A is either important in a subset of patients or plays a relatively minor role in inflammatory joint disease. Ongoing phase 3 clinical trials should provide further information on the role of IL-17A in these diseases.

15 Review Incidence of cardiovascular disease in individuals with psoriasis: a systematic review and meta-analysis. 2013

Samarasekera, Eleanor J / Neilson, Julie M / Warren, Richard B / Parnham, Jill / Smith, Catherine H. ·National Clinical Guideline Centre, Royal College of Physicians of London, London, UK. · Dermatology Centre, The University of Manchester, Manchester Academic Health Sciences Centre, Salford Royal Foundation Trust, Manchester, UK. · St John's Institute of Dermatology, Division of Medicine and Molecular Genetics, Guy's Hospital, London, UK. Electronic address: catherine.smith@kcl.ac.uk. ·J Invest Dermatol · Pubmed #23528816.

ABSTRACT: The relationship between psoriasis and increased risk of cardiovascular disease (CVD) is controversial. We critically evaluate 14 cohorts and meta-analyze the magnitude of CVD risk for the primary outcomes of CVD mortality, stroke, and myocardial infarction (MI), and establish subgroup risk for different psoriasis severities and age groups. Increased CVD risk was identified only in individuals with severe psoriasis (defined as requiring systemic therapy or hospital admission): the risk ratio relative to the general population was 1.37 (95% confidence interval (CI) 1.17-1.60) for CVD mortality, 3.04 (95% CI 0.65-14.35) for MI, and 1.59 (95% CI 1.34-1.89) for stroke. The relative risks of CVD were highest in the younger, severe psoriasis population (e.g., 3.10 (95% CI 1.98-4.86) for MI at 30 years), and absolute risks were greatest in older individuals with severe psoriasis (e.g., 23.2 excess MIs per 10,000 person-years at 60 years). Uncertainty remains about whether CVD risk is directly attributable to psoriasis, as the majority of studies failed to adequately adjust for key traditional risk factors.

16 Review Demyelination during tumour necrosis factor antagonist therapy for psoriasis: a case report and review of the literature. 2013

Mahil, Satveer K / Andrews, Thomasin C / Brierley, Charlotte / Barker, Jonathan N / Smith, Catherine H. ·St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, UK. ·J Dermatolog Treat · Pubmed #22268700.

ABSTRACT: Central nervous system (CNS) demyelination in a patient receiving tumour necrosis factor alpha (TNF-α) antagonist therapy in our practice prompted a search of the literature to assess the evidence for a causal relationship between TNF antagonist therapy and demyelination. We summarise clinical data extracted on 65 reported cases of CNS demyelination in patients receiving TNF antagonist therapy and show that the data are consistent with a drug-related aetiology given the temporal relationship between TNF antagonist initiation and symptoms, de-challenge-re-challenge phenomenon and the later age of disease onset compared with sporadic multiple sclerosis. Research on TNF signalling pathways also suggests a plausible causative role of TNF antagonist therapy in demyelination. However to date, controlled trial and pharmacovigilance data do not show an increased risk of demyelination in patients receiving TNF antagonist therapy. These data may be underpowered to exclude such a risk and pooled, collaborative data from multiple registries are warranted. Given the uncertainty in this area, clinicians should adhere to existing clinical guidance advising avoidance of TNF antagonist therapy in patients with a personal or family history of demyelination, and ensure all suitable patients are enrolled in long term safety registries in countries where these are established.

17 Review Concepts in psoriasis: psoriasis and the extracellular matrix. 2012

McFadden, J / Fry, L / Powles, A V / Kimber, I. ·Department of Cutaneous Allergy, St John's Institute of Dermatology, St Thomas' Hospital, London SE1 7EH, U.K. john.mcfadden@kcl.ac.uk ·Br J Dermatol · Pubmed #22803790.

ABSTRACT: Post-streptococcal guttate psoriasis only sometimes progresses to the persistent plaque psoriasis. We have previously proposed that psoriasis is driven by multiple extradomain A+ fibronectin (EDA+ FN) 'feedback loops'. The psoriasis-specific loop, the 'keratinocyte loop', depends upon expression by keratinocytes of α5β1 integrin. In normal skin, α5β1 expression is minimal or absent in resting epithelial cells, where basal cells are anchored to the laminin component of the basement membrane (via integrins α6β4 and α3β1). However, when the laminin layer is disrupted, due to wounding for instance, α5β1 is then strongly expressed by basal cells as a means for anchoring. At uninvolved skin sites in patients with psoriasis the laminin layer within the basement membrane is disrupted, with a consequential increase in the expression by basal keratinocytes of EDA+ FN and α5β1. We are postulating that in guttate psoriasis streptococcal lytic enzymes, and in particular streptokinase, may - via plasminogen activation - initiate a disruption of the laminin layer in the basement membrane. It is also possible that the expression by proliferating keratinocytes of plasminogen-activating factor might result in additional laminin digestion. The suggestion is that progression of guttate psoriasis to full-blown plaque psoriasis, or to its spontaneous resolution, is governed largely by the triggering of humoral immune responses. Thus, if streptococcal lytic enzymes are neutralized by host antibodies in advance of irreversible and lasting damage to the basement membrane of the dermal papillae, then guttate psoriasis will resolve spontaneously. In contrast, if permanent damage is induced prior to effective neutralization of the relevant bacterial toxins, then keratinocytes will become chronically destabilized. The consequence will be to liberate keratinocytes to proliferate in response to various stimuli, and to continue to elaborate plasminogen activation enzymes; the combined effect being, in concert with immunological priming, to precipitate and sustain plaque psoriasis.

18 Review An overview and update of psoriasis. 2011

Green, Liz. ·Skin Therapy Research Unit, St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London. ·Nurs Stand · Pubmed #21667856.

ABSTRACT: Psoriasis is a common, chronic skin condition and nurses can expect to encounter patients with psoriasis in both primary and secondary care settings. This article focuses on the physical and psychosocial effects of the condition and on appropriate management strategies, including the use of biologic therapies to treat moderate to severe psoriasis. Quality of life issues are also addressed.

19 Review How genetic variation affects patient response and outcome to therapy for psoriasis. 2010

Woolf, Richard T / Smith, Catherine H. ·St John's Institute of Dermatology, Division of Genetics and Molecular Medicine, 9th Floor Tower Wing, Guy's Hospital, Great Maze Pond Road, London, SE1 9RT, UK. ·Expert Rev Clin Immunol · Pubmed #20979559.

ABSTRACT: Psoriasis is a prevalent chronic inflammatory condition that affects the skin. There are many treatments available for psoriasis but they are not universally effective and some have associated toxicities. Pharmacogenetics and pharmacogenomics explore the relationship between individual genetic variation and drug effect to allow targeted 'personalized' therapy for patients. There has been very limited pharmacogenetic research regarding psoriasis, with most limited to small retrospective case-control studies looking at single-nucleotide polymorphisms in candidate genes involved in drug pharmacokinetics. We review the pharmacogenetic investigation of treatments for psoriasis to date, including emerging pharmacogenomic studies. In addition, we discuss how such genetic data could be incorporated into routine clinical practice and future areas for development in this field.

20 Review Psoriasis and extra domain A fibronectin loops. 2010

McFadden, J P / Baker, B S / Powles, A V / Fry, L. ·Department of Cutaneous Allergy, St John's Institute of Dermatology, St Thomas' Hospital, London SE1 7EH, UK. john.mcfadden@kcl.ac.uk ·Br J Dermatol · Pubmed #20192957.

ABSTRACT: We have previously postulated that as well as T-helper (Th) 1 and Th17 cells, the transforming growth factor (TGF)-beta/fibronectin (FN)/alpha5beta1 pathway is central to psoriasis pathogenesis. EDA+ FN refers to an alternatively spliced isoform of FN with an additional domain known as extra domain A. EDA+ FN has two important properties pertinent to psoriasis lesions: it stimulates keratinocyte hyperproliferation, and, through stimulation of Toll-like receptor (TLR) 4, stimulates production of proinflammatory cytokines. EDA+ FN production induced by TGF-beta stimulation can be maintained in psoriasis lesions via two main feedback loops. Firstly, EDA+ FN stimulates proliferation of keratinocytes, which, in an autocrine fashion, will release more EDA+ FN. Secondly, EDA+ FN stimulates TLR4 expressed by antigen-presenting cells resulting in the production of proinflammatory cytokines such as tumour necrosis factor-alpha, interleukin (IL)-1, IL-6 and IL-12. The resultant promotion of cutaneous inflammation results in the recruitment of Th1 cells, which also produce EDA+ FN. We propose that these 'FN loops' contribute to the maintenance and progression of psoriatic lesions. Finally, although the association between psoriasis and heart/thrombotic disease remains unclear one plausible link may be the promotion of atherosclerosis and thrombotic heart disease by EDA+ FN.

21 Review Psoriasis and streptococci: the natural selection of psoriasis revisited. 2009

McFadden, J P / Baker, B S / Powles, A V / Fry, L. ·Department of Cutaneous Allergy, St John's Institute of Dermatology, St Thomas' Hospital, London SE1 7EH, UK. john.mcfadden@kcl.ac.uk ·Br J Dermatol · Pubmed #19309365.

ABSTRACT: We have previously postulated that surviving invasive streptococcal infections may have been a factor in psoriasis becoming a common skin disease in some parts of the world. Many of the candidate genes linked to psoriasis are associated with the acquired or innate immune system, which are also important in host defence to invasive streptococcal infections. High rates of positive streptococcal throat swabs among patients with chronic plaque psoriasis suggest that they are efficient at internalizing/carrying beta-haemolytic streptococci. Internalization of streptococci in the throat is dependent upon the transforming growth factor (TGF)-beta/fibronectin/alpha 5 beta 1 integrin pathway. The immune cell Th17 and its related cytokine network are important in mucosal defence, being very effective against extracellular microbes but having little effect on intracellular organisms. The TGF-beta/fibronectin/alpha 5 beta 1 integrin pathway and the Th17 cell network also appear to be operative in psoriasis, animal models of both TGF-beta and alpha 5 beta 1 cutaneous overexpression being associated with characteristic psoriasis lesions. We postulate that some of the genotypic/phenotypic changes in different immunological pathways in psoriasis, including the acquired T-cell response, the innate immune response, the TGF-beta/fibronectin/alpha 5 beta 1 integrin pathway and the Th17 cell system, confer protection against mortality during epidemics of invasive streptococcal infections, heightened efficiency in internalizing and allowing carriage of streptococci as well as predisposition to the development of psoriasis.

22 Review Psoriasis. 2008

Nestle, Frank O. ·St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, King's College London School of Medicine at Guy's, Guy's Hospital, London, UK. frank.nestle@kcl.ac.uk ·Curr Dir Autoimmun · Pubmed #18460881.

ABSTRACT: Psoriasis is one of the most common chronic inflammatory disorders with a strong genetic background. Recent progress in the understanding of both the immunological as well as the genetic basis has provided an unprecedented opportunity to move scientific insights from the bench to bedside. Based on insights from laboratory research, targeted immunotherapies are now available for the benefit of patients suffering from psoriasis. The success of these therapies has validated insights into disease pathogenesis and also provides the opportunity to increase our understanding about the pathways underpinning autoimmune-type inflammation in the skin.

23 Clinical Trial Secukinumab sustains improvement in signs and symptoms of psoriatic arthritis: 2 year results from the phase 3 FUTURE 2 study. 2017

McInnes, Iain B / Mease, Philip J / Ritchlin, Christopher T / Rahman, Proton / Gottlieb, Alice B / Kirkham, Bruce / Kajekar, Radhika / Delicha, Eumorphia-Maria / Pricop, Luminita / Mpofu, Shephard. ·Institute of Infection Immunity and Inflammation, University of Glasgow, Glasgow, UK. · Division of Rheumatology Clinical Research, Swedish Medical Centre and University of Washington, Seattle, WA. · Allergy/Immunology and Rheumatology Division, University of Rochester, Rochester, NY, USA. · Faculty of Medicine, Memorial University, St. John's, NL, Canada. · Department of Dermatology, New York Medical College, Valhalla, NY, USA. · Rheumatology Department, Guy's & St Thomas' NHS Foundation Trust, London, UK. · Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. · Novartis Pharma, Basel, Switzerland. ·Rheumatology (Oxford) · Pubmed #28968735.

ABSTRACT: Objectives: To assess long-term efficacy, safety and tolerability of secukinumab up to 104 weeks in patients with active PsA. Methods: Patients with PsA (n = 397) were randomized to s.c. secukinumab 300, 150 or 75 mg or placebo at baseline, weeks 1, 2, 3 and 4 and every 4 weeks thereafter. Placebo-treated patients were re-randomized to receive secukinumab 300 or 150 mg s.c. from week 16 (placebo non-responders) or week 24 (placebo responders). Exploratory endpoints at week 104 included 20, 50 and 70% improvement in ACR criteria (ACR20, 50, 70); 75 and 90% improvement in the Psoriasis Area Severity Index, 28-joint DAS with CRP, presence of dactylitis and enthesitis and other patient-reported outcomes. For binary variables, missing values were imputed; continuous variables were analysed by a mixed-effects model for repeated measures. Results: A total of 86/100 (86%), 76/100 (76%) and 65/99 (66%) patients in the secukinumab 300, 150 and 75 mg groups, respectively, completed 104 weeks. At week 104, ACR20 response rates after multiple imputation in the 300, 150 and 75 mg groups were 69.4, 64.4 and 50.3%, respectively. Sustained clinical improvements were observed through week 104 with secukinumab across other clinically important domains of PsA. Responses were sustained through week 104 regardless of prior anti-TNF-α use. Over the entire treatment period the incidence, type and severity of adverse events were consistent with those reported previously. Conclusion: Secukinumab provided sustained improvements in signs and symptoms and multiple clinical domains in patients of active PsA through 2 years of therapy. Secukinumab was well tolerated, with a safety profile consistent with that reported previously. Trial registration: ClinicalTrials.gov (https://clinicaltrials.gov), NCT01752634.

24 Clinical Trial Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial. 2017

Nash, Peter / Kirkham, Bruce / Okada, Masato / Rahman, Proton / Combe, Benard / Burmester, Gerd-Ruediger / Adams, David H / Kerr, Lisa / Lee, Chin / Shuler, Catherine L / Genovese, Mark / Anonymous7610907. ·Department of Medicine, University of Queensland, Rheumatology Research Unit, Sunshine Coast, QLD, Australia. Electronic address: drpnash@tpg.com.au. · Guy's and St Thomas' NHS Foundation Trust, London, UK. · Immuno-Rheumatology Center, St Luke's International University, St Luke's International Hospital, Tokyo, Japan. · Department of Medicine, Memorial University, St Clare's Mercy Hospital, St John's, NL, Canada. · Departement of Rheumatology, Lapeyronie Hospital, Montpellier Université, Montpelier, France. · Department of Rheumatology and Clinical Immunology, Charite University Medicine Berlin, Campus Mitte, Berlin, Germany. · Eli Lilly and Company, Indianapolis, IN, USA. · Department of Medicine, Stanford University, Palo Alto, CA, USA. ·Lancet · Pubmed #28551073.

ABSTRACT: BACKGROUND: Patients who have had inadequate response to tumour necrosis factor inhibitors have fewer treatment options and are generally more treatment refractory to subsequent therapeutic interventions than previously untreated patients. We report the efficacy and safety of ixekizumab, a monoclonal antibody that selectively targets interleukin-17A, in patients with active psoriatic arthritis and previous inadequate response to tumour necrosis factor inhibitors. METHODS: In this double-blind, multicentre, randomised, placebo-controlled, phase 3 study (SPIRIT-P2), patients were recruited from 109 centres across ten countries in Asia, Australia, Europe, and North America. Patients were aged 18 years or older, had a confirmed diagnosis of psoriatic arthritis for at least 6 months, and had a previous inadequate response, distinguished by being refractory to therapy or had loss of efficacy, or were intolerant to tumour necrosis factor inhibitors. Patients were randomly assigned (1:1:1) by a computer-generated random sequence to receive a subcutaneous injection of 80 mg ixekizumab every 4 weeks or every 2 weeks after a 160 mg starting dose or placebo. The primary endpoint was the proportion of patients who attained at least 20% improvement in the American College of Rheumatology response criteria (ACR-20) at week 24. This study is registered with ClinicalTrials.gov, number NCT02349295. FINDINGS: Between March 3, 2015, to March 22, 2016, 363 patients were randomly assigned to placebo (n=118), ixekizumab every 4 weeks (n=122), or ixekizumab every 2 weeks (n=123). At week 24, a higher proportion of patients attained ACR-20 with ixekizumab every 4 weeks (65 [53%] patients; effect size vs placebo 33·8% [95% CI 22·4-45·2]; p<0·0001) and ixekizumab every 2 weeks (59 [48%] patients; 28.5% [17·1-39.8]; p<0·0001) than did patients with placebo (23 [20%] patients). Up to week 24, serious adverse events were reported in three (3%) patients with ixekizumab every 4 weeks, eight (7%) with ixekizumab every 2 weeks, and four (3%) with placebo; no deaths were reported. Infections were reported in 47 (39%) patients with ixekizumab every 4 weeks, 47 (38%) with ixekizumab every 2 weeks, and 35 (30%) with placebo. Three (2%) serious infections, all in patients in the ixekizumab every 2 weeks group, were reported. INTERPRETATION: Both the 2-week and 4-week ixekizumab dosing regimens improved the signs and symptoms of patients with active psoriatic arthritis and who had previously inadequate response to tumour necrosis factor inhibitors, with a safety profile consistent with previous studies investigating ixekizumab. FUNDING: Eli Lilly and Company.

25 Clinical Trial Secukinumab Inhibition of Interleukin-17A in Patients with Psoriatic Arthritis. 2015

Mease, Philip J / McInnes, Iain B / Kirkham, Bruce / Kavanaugh, Arthur / Rahman, Proton / van der Heijde, Désirée / Landewé, Robert / Nash, Peter / Pricop, Luminita / Yuan, Jiacheng / Richards, Hanno B / Mpofu, Shephard / Anonymous2430844. ·From the Swedish Medical Center and the University of Washington - both in Seattle (P.J.M.) · University of Glasgow, Glasgow (I.B.M.), and Guy's and St. Thomas' NHS Foundation Trust, London (B.K.) - both in the United Kingdom · University of California, San Diego, School of Medicine, San Diego (A.K.) · Memorial University, St. John's, NL, Canada (P.R.) · Leiden University Medical Center, Leiden (D.H.), and University of Amsterdam and Atrium Medical Center, Amsterdam (R.L.) - all in the Netherlands · University of Queensland, Brisbane, Australia (P.N.) · Novartis Pharmaceuticals, East Hanover, NJ (L.P., J.Y.) · and Novartis Pharma, Basel, Switzerland (H.B.R., S.M.). ·N Engl J Med · Pubmed #26422723.

ABSTRACT: BACKGROUND: In a phase 2 study, the inhibition of the interleukin-17A receptor improved signs and symptoms of psoriatic arthritis. We sought to evaluate the efficacy and safety of secukinumab, an anti-interleukin-17A monoclonal antibody, in such patients. METHODS: In this double-blind, phase 3 study, 606 patients with psoriatic arthritis were randomly assigned in a 1:1:1 ratio to receive intravenous secukinumab (at a dose of 10 mg per kilogram) at weeks 0, 2, and 4, followed by subcutaneous secukinumab at a dose of either 150 mg or 75 mg every 4 weeks, or placebo. Patients in the placebo group were switched to subcutaneous secukinumab at a dose of 150 mg or 75 mg at week 16 or 24, depending on clinical response. The primary end point was the proportion of patients with an American College of Rheumatology 20 (ACR20) response at week 24, defined as a 20% improvement from baseline in the number of tender and swollen joints and at least three other important domains. RESULTS: ACR20 response rates at week 24 were significantly higher in the group receiving secukinumab at doses of 150 mg (50.0%) and 75 mg (50.5%) than in those receiving placebo (17.3%) (P<0.001 for both comparisons with placebo). Secondary end points, including the ACR50 response and joint structural damage, were significantly better in the secukinumab groups than in the placebo group. Improvements were sustained through 52 weeks. Infections, including candida, were more common in the secukinumab groups. Throughout the study (mean secukinumab exposure, 438.5 days; mean placebo exposure, 128.5 days), four patients in the secukinumab groups had a stroke (0.6 per 100 patient-years; 95% confidence interval [CI], 0.2 to 1.5), and two had a myocardial infarction (0.3 per 100 patient-years; 95% CI, 0.0 to 1.0), as compared with no patients in the placebo group. CONCLUSIONS: Secukinumab was more effective than placebo in patients with psoriatic arthritis, which validates interleukin-17A as a therapeutic target. Infections were more common in the secukinumab groups than in the placebo group. The study was neither large enough nor long enough to evaluate uncommon serious adverse events or the risks associated with long-term use. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT01392326.).

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