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Psoriasis: HELP
Articles from Tyne and Wear
Based on 33 articles published since 2008
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These are the 33 published articles about Psoriasis that originated from Tyne and Wear during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Editorial Establishing an Academic-Industrial Stratified Medicine Consortium: Psoriasis Stratification to Optimize Relevant Therapy. 2015

Griffiths, Christopher E M / Barnes, Michael R / Burden, A David / Nestle, Frank O / Reynolds, Nick J / Smith, Catherine H / Warren, Richard B / Barker, Jonathan N W N / On Behalf Of The Psort Consortium, ?. ·Dermatology Centre, Salford Royal Hospital, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom. Electronic address: christopher.griffiths@manchester.ac.uk. · William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom. · Department of Dermatology, Western Infirmary, Glasgow, United Kingdom. · St. Johns Institute of Dermatology, Kings College London, London, United Kingdom. · Dermatological Sciences, Institute of Cellular Medicine, Newcastle University Medical School and Department of Dermatology, Royal Victoria Infirmary, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom. · Dermatology Centre, Salford Royal Hospital, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom. ·J Invest Dermatol · Pubmed #26569580.

ABSTRACT: -- No abstract --

2 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.

3 Review Human skin dendritic cells in health and disease. 2015

Haniffa, Muzlifah / Gunawan, Merry / Jardine, Laura. ·Institute of Cellular Medicine, Newcastle University, NE2 4HH, UK; Department of Dermatology, Newcastle Upon Tyne NHS Trust, NE1 4LP, UK. Electronic address: m.a.haniffa@ncl.ac.uk. · Institute of Cellular Medicine, Newcastle University, NE2 4HH, UK. ·J Dermatol Sci · Pubmed #25301671.

ABSTRACT: Dendritic cells (DCs) are specialized antigen presenting cells abundant in peripheral tissues such as skin where they function as immune sentinels. Skin DCs migrate to draining lymph node where they interact with naïve T cells to induce immune responses to microorganisms, vaccines, tumours and self-antigens. In this review, we present the key historical developments and recent advances in human skin DC research. We also integrate the current understanding on the origin and functional specializations of DC subsets in healthy skin with findings in inflammatory skin diseases focusing on psoriasis and atopic eczema. A comprehensive understanding of the dynamic changes in DC subsets in health and disease will form a strong foundation to facilitate the clinical translation of DC-based therapeutic and vaccination strategies.

4 Review Newer agents for psoriasis in adults. 2014

Jabbar-Lopez, Z K / Wu, K C P / Reynolds, N J. ·Dermatological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK. · Dermatological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK nick.reynolds@ncl.ac.uk. ·BMJ · Pubmed #25008099.

ABSTRACT: -- No abstract --

5 Review Topical treatments for chronic plaque psoriasis: an abridged Cochrane systematic review. 2013

Mason, Anne / Mason, James / Cork, Michael / Hancock, Helen / Dooley, Gordon. ·Center for Health Economics, University of York, York, United Kingdom. Electronic address: anne.mason@york.ac.uk. · School of Medicine, Pharmacy, and Health, Durham University, Stockton-on-Tees, United Kingdom. · Academic Unit of Dermatology Research, University of Sheffield Medical School, Sheffield, United Kingdom. · Metaxis Ltd, Curbridge, United Kingdom. ·J Am Acad Dermatol · Pubmed #24124809.

ABSTRACT: BACKGROUND: Chronic plaque psoriasis is the most common type of psoriasis and is characterized by redness, thickness, and scaling. First-line management is with topical treatments. OBJECTIVE: We sought to undertake a Cochrane review of topical treatments for chronic plaque psoriasis. METHODS: We systematically searched major databases for randomized controlled trials. Trials reported improvement using a range of related measures; standardized, pooled findings were translated onto a 6-point improvement scale. RESULTS: The review included 177 randomized controlled trials with 34,808 participants, including 26 trials of scalp psoriasis and 6 trials of inverse and/or facial psoriasis. Typical trial duration was 3 to 8 weeks. When compared with placebo (emollient base), the average improvement for vitamin-D analogues and potent corticosteroids was approximately 1 point, dithranol 1.2 points, very potent corticosteroids 1.8 points, and combined vitamin-D analogue plus steroid 1.4 points once daily and 2.2 points twice daily. However, these are indicative benefits drawn from heterogeneous trial findings. Corticosteroids were more effective than vitamin D for treating psoriasis of the scalp. For both body and scalp psoriasis, potent corticosteroids were less likely than vitamin D to cause skin irritation. LIMITATIONS: Reporting of benefits, adverse effects, and safety assessment methods was often inadequate. In many comparisons, heterogeneity made the size of treatment benefit uncertain. CONCLUSIONS: Corticosteroids are as effective as vitamin-D analogues and cause less skin irritation. However, further research is needed to inform long-term maintenance treatment and provide appropriate safety data.

6 Clinical Trial Autologous tolerogenic dendritic cells for rheumatoid and inflammatory arthritis. 2017

Bell, G M / Anderson, A E / Diboll, J / Reece, R / Eltherington, O / Harry, R A / Fouweather, T / MacDonald, C / Chadwick, T / McColl, E / Dunn, J / Dickinson, A M / Hilkens, C M U / Isaacs, John D. ·Arthritis Research UK Rheumatoid Arthritis Pathogenesis Centre of Excellence (RACE), Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle upon Tyne, UK. · Institute of Health and Society, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK. · Clinical Trials Unit, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK. · Haematological Sciences, Institute of Cellular Medicine, Newcastle upon Tyne, UK. ·Ann Rheum Dis · Pubmed #27117700.

ABSTRACT: OBJECTIVES: To assess the safety of intra-articular (IA) autologous tolerogenic dendritic cells (tolDC) in patients with inflammatory arthritis and an inflamed knee; to assess the feasibility and acceptability of the approach and to assess potential effects on local and systemic disease activities. METHODS: An unblinded, randomised, controlled, dose escalation Phase I trial. TolDC were differentiated from CD14+ monocytes and loaded with autologous synovial fluid as a source of autoantigens. Cohorts of three participants received 1×10 RESULTS: There were no target knee flares within 5 days of treatment. At day 14, arthroscopic synovitis was present in all participants except for one who received 10×10 CONCLUSION: IA tolDC therapy appears safe, feasible and acceptable. Knee symptoms stabilised in two patients who received 10×10 TRIAL REGISTRATION NUMBER: NCT01352858.

7 Clinical Trial Investigation of cutaneous photoadaptation to narrowband ultraviolet B. 2014

Darné, S / Stewart, L C / Farr, P M / Hampton, P J. ·Royal Victoria Infirmary, Newcastle upon Tyne, U.K. ·Br J Dermatol · Pubmed #24125495.

ABSTRACT: BACKGROUND: Photoadaptation describes the skin's ability to withstand an increased dose of ultraviolet (UV) radiation with repeated exposure, and this is the reason for exposure doses being increased during a course of phototherapy. However, directly measured data on photoadaptation are available only for broadband (BB) and not narrowband (NB)-UVB. OBJECTIVES: To measure photoadaptation to narrowband UVB. METHODS: We measured the degree of photoadaptation in patients with psoriasis during a standard course of NB-UVB phototherapy. The minimal erythemal dose (MED) was measured before and towards the end of a course of phototherapy. An adaptation factor (AF) was calculated for each patient using the ratio of final MED to initial MED. Sigmoid dose-response curves were also constructed. RESULTS: MED results were available for 50 patients (mean age 44 years, 28 female). The mean AF was 2·7 (95% confidence interval 2·4-3·0). There was no significant correlation between AF and skin type or initial MED. Dose-response curves were right shifted and parallel after phototherapy, and there was no significant difference in the maximum slope (P = 0·73). CONCLUSIONS: The photoadaptation caused by NB-UVB is considerably less than that reported for BB-UVB. The variation in photoadaptation between patients was not explained by skin type or baseline MED. Physical factors (such as tanning and epidermal thickening) are probably sufficient to account for photoadaptation, rather than downregulation of the inflammatory response. These data should help in the design of phototherapy protocols for NB-UVB to achieve optimal clearance of psoriasis.

8 Clinical Trial Keratinocyte apoptosis in epidermal remodeling and clearance of psoriasis induced by UV radiation. 2011

Weatherhead, Sophie C / Farr, Peter M / Jamieson, David / Hallinan, Jennifer S / Lloyd, James J / Wipat, Anil / Reynolds, Nick J. ·Dermatological Sciences, Institute of Cellular Medicine, Newcastle University Medical School, Newcastle upon Tyne, UK. ·J Invest Dermatol · Pubmed #21614017.

ABSTRACT: Psoriasis is a common chronic skin disorder, but the mechanisms involved in the resolution and clearance of plaques remain poorly defined. We investigated the mechanism of action of UVB, which is highly effective in clearing psoriasis and inducing remission, and tested the hypothesis that apoptosis is a key mechanism. To distinguish bystander effects, equal erythemal doses of two UVB wavelengths were compared following in vivo irradiation of psoriatic plaques; one is clinically effective (311  nm) and one has no therapeutic effect on psoriasis (290  nm). Only 311  nm UVB induced significant apoptosis in lesional epidermis, and most apoptotic cells were keratinocytes. To determine clinical relevance, we created a computational model of psoriatic epidermis. Modeling predicted apoptosis would occur in both stem and transit-amplifying cells to account for plaque clearance; this was confirmed and quantified experimentally. The median rate of keratinocyte apoptosis from onset to cell death was 20  minutes. These data were fed back into the model and demonstrated that the observed level of keratinocyte apoptosis was sufficient to explain UVB-induced plaque resolution. Our human studies combined with a systems biology approach demonstrate that keratinocyte apoptosis is a key mechanism in psoriatic plaques clearance, providing the basis for future molecular investigation and therapeutic development.

9 Article A small population, randomised, placebo-controlled trial to determine the efficacy of anakinra in the treatment of pustular psoriasis: study protocol for the APRICOT trial. 2018

Cornelius, Victoria / Wilson, Rosemary / Cro, Suzie / Barker, Jonathan / Burden, David / Griffiths, Christopher E M / Lachmann, Helen / McAteer, Helen / Reynolds, Nick / Pink, Andrew / Warren, Richard B / Capon, Francesca / Smith, Catherine. ·Imperial Clinical Trials Unit, School of Public Health, Imperial College London, Stadium House, 68 Wood Lane, London, W12 7RH, UK. v.cornelius@imperial.ac.uk. · St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, 9th Floor Tower Wing, Guy's Hospital, London, UK. · Imperial Clinical Trials Unit, School of Public Health, Imperial College London, Stadium House, 68 Wood Lane, London, W12 7RH, UK. · St John's Institute of Dermatology, Faculty of Life Sciences and Medicine, King's College London, London, UK. · Department of Dermatology, Royal Infirmary, Edinburgh, UK. · The Dermatology Centre, Salford Royal NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. · National Amyloidosis Centre, University College London, Royal Free Campus, London, UK. · The Psoriasis Association, Dick Coles House, 2 Queensbridge, Northampton, UK. · Institute of Cellular Medicine, Department of Dermatology, Newcastle University, Newcastle upon Tyne, UK. · Department of Medical & Molecular Genetics, King's College London, 9th Floor Tower Wing, Guy's Hospital, Great Maze Pond, London, UK. ·Trials · Pubmed #30157880.

ABSTRACT: BACKGROUND: Palmoplantar pustulosis is a rare but painful and debilitating disease. It consistently ranks the highest of all psoriasis phenotypic variants in terms of symptoms and functional impairment. Management of plaque-type psoriasis has been revolutionised in the last 10 years with the advent of biologic therapies, but treatment options for pustular psoriasis remain profoundly limited. On the basis of mechanistic findings which suggest a key pathogenic role for interleukin (IL)-1 in pustular psoriasis, we hypothesise that anakinra (IL-1 blockade) will be an efficacious treatment for pustular psoriasis. METHODS/DESIGN: We will conduct a two-stage, adaptive, double-blind, randomised, placebo-controlled trial to test the hypothesis that anakinra, self-administered daily by subcutaneous injection over 8 weeks, will deliver therapeutic benefit in palmoplantar pustular psoriasis, a localised form of pustular psoriasis typically involving the palms and/or soles. Safety outcomes will be collected for 20 weeks. A total of 64 participants will be randomised to anakinra or placebo in a 1:1 ratio. At the end of stage 1, a decision to progress to stage 2 will be made. This decision will take place after 24 participants have been randomised and followed for 8 weeks and will be based on the ordering of the observed mean outcome values in both treatment arms. At the end of stage 1, the reliability of outcome measurements and method to collect the data will also be assessed, and the primary outcome will be confirmed for stage 2. DISCUSSION: We have undertaken an adaptive approach in which we will gain proof-of-concept data prior to completing a powered efficacy trial because pustular psoriasis is a rare disease, no validated outcome measures to detect change exist, and limited safety data for anakinra exist in this population. To our knowledge, this will be the first randomised controlled trial that will provide valuable evidence for the efficacy and safety of IL-1 blockade for treatment in pustular psoriasis. TRIAL REGISTRATION: ISRCTN13127147 . Registered on 1st August 2016. EudraCT, 2015-003600-23 . Registered on 1st April 2016.

10 Article Comparison of Drug Discontinuation, Effectiveness, and Safety Between Clinical Trial Eligible and Ineligible Patients in BADBIR. 2018

Mason, Kayleigh J / Barker, Jonathan N W N / Smith, Catherine H / Hampton, Philip J / Lunt, Mark / McElhone, Kathleen / Warren, Richard B / Yiu, Zenas Z N / Griffiths, Christopher E M / Burden, A David / Anonymous1241208. ·Division of Musculoskeletal and Dermatological Sciences, The University of Manchester, Manchester, United Kingdom. · St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom. · Newcastle Dermatology, Newcastle Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom. · Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester, United Kingdom. · Centre for Pharmacoepidemiology and Drug Safety, The University of Manchester, Manchester, United Kingdom. · Department of Dermatology, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom. ·JAMA Dermatol · Pubmed #29590279.

ABSTRACT: Importance: Patients with psoriasis enrolled in clinical trials of biologics may not be representative of the real-world population. There is evidence that patients ineligible for such trials have a greater risk of serious adverse events (SAEs), but the effect on drug discontinuation and effectiveness are unknown. Objective: To determine whether (1) drug discontinuation, (2) effectiveness, and (3) rates of SAEs differ in patients with psoriasis categorized as eligible or ineligible for clinical trials. Design, Setting, and Participants: An observational study using 157 dermatology centers in the United Kingdom and Republic of Ireland was carried out wherein we applied the eligibility criteria of clinical trials of biologic therapies for psoriasis to patients who were being followed up in the British Association of Dermatologists Biologic Interventions Register (BADBIR) and being prescribed biologics as part of standard clinical care. Patients with psoriasis registered to BADBIR who were taking etanercept (enbrel only; n = 1509), adalimumab (n = 4000), and ustekinumab (n = 1627) with at least 1 follow-up visit. Eligibility criteria were extracted from phase 3 licensing trials for etanercept, adalimumab, and ustekinumab for the treatment of moderate to severe psoriasis. Patients in BADBIR with a missing baseline Psoriasis Area and Severity Index (PASI) or baseline PASI value less than 10 (etanercept) or less than 12 (adalimumab; ustekinumab) but who would otherwise be eligible were investigated separately. Eligibility categories applied to BADBIR included: eligible, ineligible, insufficient baseline PASI only, and missing baseline PASI only. Main Outcomes and Measures: (1) Drug discontinuation: cumulative incidence at 12 months by stop reason per eligibility category and drug; (2) effectiveness: linear regression of absolute change in PASI from baseline to 6 and 12 months; and (3) SAEs: incidence rate ratio (IRR) at 12 months between eligibility categories per drug. Results: The mean (SD) age of the 7136 patients included in the analysis was 45 (13) years and 2924 (41%) were women and 4212 (59%) were men. Of 7136 patients, 839 (56%) etanercept, 2219 (56%) adalimumab, and 754 (46%) ustekinumab registrations were categorized as eligible. The most common reasons for ineligibility were diabetes (etanercept, 143 [9%]; ustekinumab, 201 [12%]) and nonchronic plaque psoriasis (adalimumab, 157 [4%]). Patients categorized as ineligible (etanercept, 367 [24%]; adalimumab, 282 [7%]; ustekinumab, 394 [24%]) achieved a smaller absolute change in PASI after 6 and 12 months (adalimumab, ustekinumab), and had significantly higher rates of SAEs compared with the eligible category (etanercept: IRR, 1.9; 95% CI, 1.4-2.6; adalimumab: IRR, 2.0; 95% CI, 1.5-2.6; ustekinumab: IRR, 2.8; 95% CI, 2.1-3.8). No significant differences in drug discontinuation were observed between categories. Conclusions and Relevance: Clinical trial effectiveness and safety outcomes are not representative of real-world patients in BADBIR patients categorized as ineligible for such trials.

11 Article Differential Drug Survival of Second-Line Biologic Therapies in Patients with Psoriasis: Observational Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR). 2018

Iskandar, Ireny Y K / Warren, Richard B / Lunt, Mark / Mason, Kayleigh J / Evans, Ian / McElhone, Kathleen / Smith, Catherine H / Reynolds, Nick J / Ashcroft, Darren M / Griffiths, Christopher E M / Anonymous5531151. ·Centre for Pharmacoepidemiology and Drug Safety, Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK. Electronic address: ireny.iskandar@manchester.ac.uk. · Dermatology Centre, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK; Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences and NIHR Manchester Biomedical Research Centre, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK. · Arthritis Research UK Epidemiology Unit, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK. · Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences and NIHR Manchester Biomedical Research Centre, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK. · St. John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, UK. · Institute of Cellular Medicine, Medical School, Newcastle University, NIHR Newcastle Biomedical Research Centre Newcastle upon Tyne, UK; Department of Dermatology, Royal Victoria Infirmary, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. · Centre for Pharmacoepidemiology and Drug Safety, Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK. · Dermatology Centre, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK; Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences and NIHR Manchester Biomedical Research Centre, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK. Electronic address: christopher.griffiths@manchester.ac.uk. ·J Invest Dermatol · Pubmed #29080680.

ABSTRACT: Little is known about the drug survival of second-line biologic therapies for psoriasis in routine clinical practice. We assessed drug survival of second-line biologic therapies and estimated the risk of recurrent discontinuation due to adverse events or ineffectiveness in patients with psoriasis who had failed a first biologic therapy and switched to a second in a large, multicenter pharmacovigilance registry (n = 1,239; adalimumab, n = 538; etanercept, n = 104; ustekinumab, n = 597). The overall drug survival rate in the first year after switching was 77% (95% confidence interval = 74-79%), falling to 58% (55-61%) in the third year. Female sex, multiple comorbidities, concomitant therapy with cyclosporine, and a high Psoriasis Area and Severity Index at switching to the second-line biologic therapy were predictors of overall discontinuation (multivariable Cox proportional hazard model). Compared to adalimumab, patients receiving etanercept were more likely to discontinue therapy (hazard ratio = 1.87, 95% confidence interval = 1.24-2.83), whereas patients receiving ustekinumab were more likely to persist (hazard ratio = 0.46; 95% confidence interval = 0.33-0.64). Discontinuation of the first biologic therapy because of adverse events was associated with an increased rate of second drug discontinuation because of adverse events (hazard ratio = 2.55; 95% confidence interval = 1.50-4.32). In conclusion, drug survival rates differed among biologic therapies and decreased over time; second-line discontinuation because of adverse events was more common among those who discontinued first-line treatment for this reason. The results of this study should support clinical decision making when choosing second-line biologic therapy for patients with psoriasis.

12 Article Risk of Serious Infection in Patients with Psoriasis Receiving Biologic Therapies: A Prospective Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR). 2018

Yiu, Zenas Z N / Smith, Catherine H / Ashcroft, Darren M / Lunt, Mark / Walton, Shernaz / Murphy, Ruth / Reynolds, Nick J / Ormerod, Anthony D / Griffiths, Christopher E M / Warren, Richard B / Anonymous451088. ·Dermatology Centre, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, NIHR Manchester Biomedical Research Centre, Manchester, UK; Centre for Pharmacoepidemiology and Drug Safety, School of Health Sciences, The University of Manchester, Manchester, UK. Electronic address: zenas.yiu@manchester.ac.uk. · St. John's Institute of Dermatology, Guy's and St. Thomas' NHS Foundation Trust, London, UK. · Centre for Pharmacoepidemiology and Drug Safety, School of Health Sciences, The University of Manchester, Manchester, UK. · Arthritis Research UK Epidemiology unit, The University of Manchester, Manchester, UK. · Department of Dermatology, Castle Hill Hospital, Hull, UK. · Sheffield University Teaching Hospitals and Sheffield Children's Hospitals, Sheffield, UK. · Dermatological Sciences, Institute of Cellular Medicine, Medical School, Newcastle University, and Department of Dermatology, Royal Victoria Infirmary, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. · Division of Applied Medicine, University of Aberdeen, Foresterhill, Aberdeen, UK. · Dermatology Centre, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, NIHR Manchester Biomedical Research Centre, Manchester, UK. · Dermatology Centre, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, NIHR Manchester Biomedical Research Centre, Manchester, UK. Electronic address: richard.warren@manchester.ac.uk. ·J Invest Dermatol · Pubmed #29054603.

ABSTRACT: Serious infection is a concern for patients with psoriasis receiving biologic therapies. We assessed the risk of serious infections for biologics used to treat psoriasis by comparison with a cohort receiving non-biologic systemic therapies in a propensity score-weighted Cox proportional hazards model using data from the British Association of Dermatologists Biologic Interventions Register. Overall, 1,352; 3,271; and 994 participants were included in the etanercept, adalimumab, ustekinumab cohorts, respectively, and 3,421 participants were in the non-biologic cohort. A total of 283 patients had a serious infection; the incidence rates with 95% confidence intervals (CI) per 1,000 person-years were as follows: non-biologic, 14.2 (11.5-17.4); etanercept, 15.3 (11.6-20.1); adalimumab, 13.9 (11.4-16.6); and ustekinumab, 15.1 (10.8-21.1). No significant increases in the risk of serious infection were observed for etanercept (hazard ratio [HR] = 1.10, 95% CI = 0.75-1.60), adalimumab (HR = 0.93, 95% CI = 0.69-1.26), or ustekinumab (HR = 0.92, 95% CI = 0.60-1.41) compared with non-biologic systemic therapies or methotrexate-only (etanercept: HR = 1.47, 95% CI = 0.95-2.28; adalimumab: HR = 1.26, 95% CI = 0.86-1.84; ustekinumab: HR = 1.22, 95% CI = 0.75-1.99). The risk of serious infection should not be a key discriminator for patients and clinicians when choosing between non-biologic systemic therapies, etanercept, adalimumab, and ustekinumab for the treatment of psoriasis.

13 Article Exome-wide association study reveals novel psoriasis susceptibility locus at TNFSF15 and rare protective alleles in genes contributing to type I IFN signalling. 2017

Dand, Nick / Mucha, Sören / Tsoi, Lam C / Mahil, Satveer K / Stuart, Philip E / Arnold, Andreas / Baurecht, Hansjörg / Burden, A David / Callis Duffin, Kristina / Chandran, Vinod / Curtis, Charles J / Das, Sayantan / Ellinghaus, David / Ellinghaus, Eva / Enerback, Charlotta / Esko, Tõnu / Gladman, Dafna D / Griffiths, Christopher E M / Gudjonsson, Johann E / Hoffman, Per / Homuth, Georg / Hüffmeier, Ulrike / Krueger, Gerald G / Laudes, Matthias / Lee, Sang Hyuck / Lieb, Wolfgang / Lim, Henry W / Löhr, Sabine / Mrowietz, Ulrich / Müller-Nurayid, Martina / Nöthen, Markus / Peters, Annette / Rahman, Proton / Reis, André / Reynolds, Nick J / Rodriguez, Elke / Schmidt, Carsten O / Spain, Sarah L / Strauch, Konstantin / Tejasvi, Trilokraj / Voorhees, John J / Warren, Richard B / Weichenthal, Michael / Weidinger, Stephan / Zawistowski, Matthew / Nair, Rajan P / Capon, Francesca / Smith, Catherine H / Trembath, Richard C / Abecasis, Goncalo R / Elder, James T / Franke, Andre / Simpson, Michael A / Barker, Jonathan N. ·Division of Genetics and Molecular Medicine, Faculty of Life Sciences & Medicine, King's College London, London, UK. · Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany. · Department of Dermatology. · Department of Computational Medicine & Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USA. · Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA. · St John's Institute of Dermatology, Faculty of Life Sciences & Medicine, King's College London, London, UK. · Clinic and Polyclinic of Dermatology, University Medicine Greifswald, Greifswald, Germany. · Department of Dermatology, Venereology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. · Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK. · Department of Dermatology, University of Utah, Salt Lake City, UT, USA. · Department of Medicine. · Department of Laboratory Medicine and Pathobiology. · Institute of Medical Science, University of Toronto, Toronto, ON, Canada. · Krembil Research Institute, University Health Network, Toronto, ON, Canada. · NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, London, UK. · Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. · Division of Cell Biology and Dermatology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. · Estonian Biobank, Estonian Genome Center, University of Tartu, Tartu, Estonia. · Dermatology Centre, Salford Royal Hospital, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK. · Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland. · Institute of Human Genetics, University of Bonn, Bonn, Germany. · Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany. · Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany. · I. Department of Medicine. · Institute of Epidemiology and Biobank PopGen, Christian-Albrechts-University of Kiel, Kiel, Germany. · Department of Dermatology, Henry Ford Hospital, Detroit, MI, USA. · Institute of Genetic Epidemiology, Helmholtz Zentrum Munich, Neuherberg, Germany. · Memorial University of Newfoundland, St. John's, NL, Canada. · Dermatological Sciences, Institute of Cellular Medicine, Newcastle University Medical School, Newcastle upon Tyne, UK. · Department of Dermatology, Royal Victoria Infirmary, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. · Institute for Community Medicine, Study of Health in Pomerania/KEF, University Medicine Greifswald, Greifswald, Germany. · Dermatology Centre, Salford Road NHS Foundation Trust, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK. · Department of Dermatology, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany. · Ann Arbor Veterans Hospital, Ann Arbor, MI, USA. ·Hum Mol Genet · Pubmed #28973304.

ABSTRACT: Psoriasis is a common inflammatory skin disorder for which multiple genetic susceptibility loci have been identified, but few resolved to specific functional variants. In this study, we sought to identify common and rare psoriasis-associated gene-centric variation. Using exome arrays we genotyped four independent cohorts, totalling 11 861 psoriasis cases and 28 610 controls, aggregating the dataset through statistical meta-analysis. Single variant analysis detected a previously unreported risk locus at TNFSF15 (rs6478108; P = 1.50 × 10-8, OR = 1.10), and association of common protein-altering variants at 11 loci previously implicated in psoriasis susceptibility. We validate previous reports of protective low-frequency protein-altering variants within IFIH1 (encoding an innate antiviral receptor) and TYK2 (encoding a Janus kinase), in each case establishing a further series of protective rare variants (minor allele frequency < 0.01) via gene-wide aggregation testing (IFIH1: pburden = 2.53 × 10-7, OR = 0.707; TYK2: pburden = 6.17 × 10-4, OR = 0.744). Both genes play significant roles in type I interferon (IFN) production and signalling. Several of the protective rare and low-frequency variants in IFIH1 and TYK2 disrupt conserved protein domains, highlighting potential mechanisms through which their effect may be exerted.

14 Article Comparative effectiveness of biological therapies on improvements in quality of life in patients with psoriasis. 2017

Iskandar, I Y K / Ashcroft, D M / Warren, R B / Lunt, M / McElhone, K / Smith, C H / Reynolds, N J / Griffiths, C E M. ·Centre for Pharmacoepidemiology and Drug Safety, Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, U.K. · Dermatology Centre, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, Manchester, U.K. · Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, U.K. · NIHR Manchester Biomedical Research Centre, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, U.K. · Arthritis Research U.K. Centre for Epidemiology, Division of Musculoskeletal and Dermatological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, U.K. · St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, U.K. · Institute of Cellular Medicine, Medical School, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, U.K. · NIHR Newcastle Biomedical Research Centre, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, U.K. · Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, U.K. ·Br J Dermatol · Pubmed #28369707.

ABSTRACT: BACKGROUND: Evidence of the comparative effectiveness of biological therapies for psoriasis on health-related quality of life (HRQoL) in routine clinical practice is limited. OBJECTIVES: To examine the comparative effectiveness of adalimumab, etanercept and ustekinumab on HRQoL in patients with psoriasis, and to identify potential predictors for improved HRQoL. METHODS: This was a prospective cohort study in which changes in HRQoL were assessed using the Dermatology Life Quality Index (DLQI) and EuroQoL-5D (EQ-5D) at 6 and 12 months. Multivariable regression models were developed to identify factors associated with achieving a DLQI of 0/1 and improvements in the EQ-5D utility score. RESULTS: In total, 2152 patients with psoriasis were included, with 1239 patients on adalimumab, 517 on etanercept and 396 on ustekinumab; 81% were biologic naïve. For the entire cohort, the median (interquartile range) DLQI and EQ-5D improved from 18 (13-24) and 0·73 (0·69-0·80) at baseline to 2 (0-7) and 0·85 (0·69-1·00) at 6 months, respectively (P < 0·001). Similar improvements were achieved at 12 months. At 12 months, multivariable regression modelling showed that female sex, multiple comorbidities, smoking and a higher DLQI or a lower EQ-5D utility score at baseline predicted a lower likelihood of achieving a DLQI of 0/1 or improvement in the EQ-5D. Compared with adalimumab, patients receiving etanercept, but not ustekinumab, were less likely to achieve a DLQI of 0/1. There was no significant difference between the biological therapies in EQ-5D improvement. CONCLUSIONS: In routine clinical practice biological therapies produce marked improvement in HRQoL, which is influenced by the choice of biological therapy, baseline impairment in HRQoL, lifestyle characteristics and comorbidities. These findings should help inform selection of optimal biological therapy for patients related to improvements in HRQoL.

15 Article High prevalence of alcohol use disorders in patients with inflammatory skin diseases. 2017

Al-Jefri, K / Newbury-Birch, D / Muirhead, C R / Gilvarry, E / Araújo-Soares, V / Reynolds, N J / Kaner, E / Hampton, P J. ·Newcastle Dermatology, Newcastle University and Newcastle Dermatology, Newcastle Hospitals NHS Trust, Newcastle upon Tyne, U.K. · Health and Social Care Institute, Teesside University, Middlesbrough, U.K. · Institute of Health and Society, Newcastle University, Newcastle upon Tyne, U.K. · Institute of Cellular Medicine, Newcastle University and Newcastle Dermatology, Newcastle Hospitals NHS Trust, Newcastle upon Tyne, U.K. ·Br J Dermatol · Pubmed #28346655.

ABSTRACT: BACKGROUND: There is a known association between psoriasis and heavy alcohol consumption. The association between heavy alcohol consumption and other inflammatory skin diseases remains to be defined. OBJECTIVES: To examine the prevalence of heavy drinking using the Alcohol Use Disorders Identification Test (AUDIT) in patients with inflammatory skin disease. METHODS: We conducted an observational cross-sectional study in a single hospital outpatient department. We recruited 609 patients with either psoriasis, eczema, cutaneous lupus or other inflammatory disorders, and a reference population with skin lesions. Primary outcome was the proportion of patients in each group with an alcohol use disorder (AUD). RESULTS: The observed prevalence of AUD was 30·6% in patients with psoriasis, 33·3% in those with eczema, 12·3% in those with cutaneous lupus, 21·8% in those with other inflammatory disease and 14·3% in those with non-inflammatory disease. Odds ratios (OR) for AUD in patients in the inflammatory groups compared with those in the noninflammatory groups, adjusted for age and sex, were as follows: psoriasis 1·65 [95% confidence interval (CI) 0·86-3·17], eczema 2·00 (95% CI 1·03-3·85), lupus 1·03 (95% CI 0·39-2·71), other inflammatory disease 1·32 (95% CI 0·68-2·56). ORs were reduced if also adjusted for Dermatology Life Quality Index (DLQI). The prevalence of DLQI ≥ 11 was 31·1% for psoriasis, 43·7% for eczema, 17·5% for cutaneous lupus, 17·2% for other inflammatory disease and 2·8% for noninflammatory disease. CONCLUSIONS: Patients with eczema attending a hospital clinic have been shown to have high levels of AUD of a similar level to patients with psoriasis and higher than patients with noninflammatory skin diseases.

16 Article Effect of anti-TNF and conventional synthetic disease-modifying anti-rheumatic drug treatment on work disability and clinical outcome in a multicentre observational cohort study of psoriatic arthritis. 2017

Tillett, William / Shaddick, Gavin / Jobling, Amelia / Askari, Ayman / Cooper, Annie / Creamer, Paul / Clunie, Gavin / Helliwell, Philip S / James, Jana / Kay, Lesley / Korendowych, Eleanor / Lane, Suzanne / Packham, Jonathon / Shaban, Ragai / Thomas, Matthew L / Williamson, Lyn / McHugh, Neil. ·Department of Rheumatology, Royal National Hospital for Rheumatic Diseases. · Department of Pharmacy and Pharmacology. · Department of Mathematics, University of Bath, Bath. · Department of Rheumatology, Robert Jones and Agnes Hunt Hospital, Shropshire. · Department of Rheumatology, Queen Alexandra Hospital, Portsmouth. · Department of Rheumatology, North Bristol NHS Foundation Trust, Bristol. · Department of Rheumatology, Cambridge University Hospitals NHS Foundation Trust, Cambridge. · Department of Rheumatology, NIHR Leeds Biomedical Research Unit, University of Leeds and Leeds Teaching Hospitals NHS Trust, Leeds. · Department of Rheumatology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne. · Department of Rheumatology, Ipswich Hospital NHS Trust, Ipswich. · Department of Rheumatology, Haywood Rheumatology Centre, Stoke-on-Trentand. · Department of Rheumatology, Great Western Hospitals NHS Foundation Trust, Swindon, UK. ·Rheumatology (Oxford) · Pubmed #28013211.

ABSTRACT: Objectives: To determine the effect of medical treatment on work disability in patients with active PsA in a real-world setting. Methods: Four hundred patients with active PsA commencing or switching to anti-TNF or conventional synthetic DMARD (csDMARD) were recruited to a multicentre UK prospective observational cohort study. Work disability was measured using the work productivity and activity-specific health problem instrument and peripheral joint activity was measured with the disease activity in PsA composite measure. Results: Four hundred patients were recruited, of whom 229 (57.25%) were working (of any age). Sixty-two patients of working age (24%) were unemployed. At 6 months there was a 10% improvement in presenteeism ( P = 0.007) and a 15% improvement in work productivity ( P = 0.001) among working patients commenced on csDMARDs ( n = 164) vs a larger and more rapid 30% improvement in presenteeism ( P < 0.001) and 40% improvement in work productivity ( P < 0.001) among those commenced on anti-TNF therapy ( n = 65). Clinical response was poor among patients commenced on a csDMARD ( n = 272), with an 8.4 point improvement in disease activity in PsA ( P < 0.001) vs those commenced on anti-TNF therapy ( n = 121), who had a 36.8 point improvement ( P < 0.001). Conclusion: We report significant and clinically meaningful improvements in both work disability and clinical outcomes after commencement of anti-TNF therapy in a real-world setting. Improvements in all outcomes among those commencing csDMARDs were slower and of a smaller magnitude.

17 Article Patterns of biologic therapy use in the management of psoriasis: cohort study from the British Association of Dermatologists Biologic Interventions Register (BADBIR). 2017

Iskandar, I Y K / Ashcroft, D M / Warren, R B / Evans, I / McElhone, K / Owen, C M / Burden, A D / Smith, C H / Reynolds, N J / Griffiths, C E M. ·Centre for Pharmacoepidemiology and Drug Safety, Manchester Pharmacy School, The University of Manchester, Manchester Academic Health Science Centre, Room 1·134, 1st Floor, Stopford Building, Oxford Road, Manchester, M13 9PT, U.K. · Dermatology Centre, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, Manchester, U.K. · Department of Dermatology, East Lancashire Hospitals NHS Trust, Royal Blackburn Hospital, Blackburn, U.K. · Department of Dermatology, Western Infirmary, Glasgow, U.K. · St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, U.K. · Dermatological Sciences, Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne, U.K. · Department of Dermatology, Royal Victoria Infirmary, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, U.K. ·Br J Dermatol · Pubmed #27589476.

ABSTRACT: BACKGROUND: Treatment modifications, including dose escalations, dose reductions, switches, discontinuations and restarts of biologics may be necessary in the management of psoriasis but the patterns of usage are incompletely defined. OBJECTIVES: To examine the treatment utilization patterns of adalimumab, etanercept and ustekinumab among biologic-naïve and non-naïve patients with psoriasis enrolled in the British Association of Dermatologists Biologic Interventions Register (BADBIR). METHODS: The study cohort included adults with chronic plaque psoriasis who were followed up for ≥ 12 months. Treatment modifications were assessed during the first year of therapy. The time-trend method, comparing the cumulative dose (CD) patients received with the recommended cumulative dose (RCD), was used to assess dosing patterns. Concomitant use of other systemic treatments was also examined. RESULTS: In total, 2980 patients (adalimumab: 1675; etanercept: 996; ustekinumab: 309) were included; 79·2% were biologic-naïve. Over 12 months, 77·4% of patients continued the biologic, 2·6% restarted therapy after a break of ≥ 90 days, 2·5% discontinued, and 17·5% switched biologic therapy. Most patients (85·7%) received the RCD of the biologic, although 8·1% were exposed to a higher CD. In total, 749 (25·1%) patients used conventional systemic therapies concomitantly with a biologic at some stage; methotrexate was used most commonly (458; 61·2%). Of those using combination therapy, 454 (60·6%) continued the use of the conventional systemic therapy for > 120 days after the start of the biologic. CONCLUSIONS: More than one-third of patients experienced treatment modifications within the first year of initiating a biologic. Conventional systemic therapies, particularly methotrexate, were commonly used concurrently, which should be considered when evaluating treatment response and adverse events to biologics in real-world observational studies.

18 Article Capture Hi-C identifies a novel causal gene, IL20RA, in the pan-autoimmune genetic susceptibility region 6q23. 2016

McGovern, Amanda / Schoenfelder, Stefan / Martin, Paul / Massey, Jonathan / Duffus, Kate / Plant, Darren / Yarwood, Annie / Pratt, Arthur G / Anderson, Amy E / Isaacs, John D / Diboll, Julie / Thalayasingam, Nishanthi / Ospelt, Caroline / Barton, Anne / Worthington, Jane / Fraser, Peter / Eyre, Stephen / Orozco, Gisela. ·Arthritis Research UK Centre for Genetics and Genomics, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT, UK. · Nuclear Dynamics Programme, The Babraham Institute, Cambridge, CB22 3AT, UK. · NIHR Manchester Musculoskeletal BRU, Manchester Academic Health Sciences Centre, Central Manchester Foundation Trust, Manchester, UK. · Institute of Cellular Medicine (Musculoskeletal Research Group), Newcastle University, Newcastle upon Tyne, NE2 4HH, UK. · Center of Experimental Rheumatology Department of Rheumatology, University Hospital of Zurich, Wagistrasse 14, 8952, Schlieren, Switzerland. · Arthritis Research UK Centre for Genetics and Genomics, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT, UK. gisela.orozco@manchester.ac.uk. ·Genome Biol · Pubmed #27799070.

ABSTRACT: BACKGROUND: The identification of causal genes from genome-wide association studies (GWAS) is the next important step for the translation of genetic findings into biologically meaningful mechanisms of disease and potential therapeutic targets. Using novel chromatin interaction detection techniques and allele specific assays in T and B cell lines, we provide compelling evidence that redefines causal genes at the 6q23 locus, one of the most important loci that confers autoimmunity risk. RESULTS: Although the function of disease-associated non-coding single nucleotide polymorphisms (SNPs) at 6q23 is unknown, the association is generally assigned to TNFAIP3, the closest gene. However, the DNA fragment containing the associated SNPs interacts through chromatin looping not only with TNFAIP3, but also with IL20RA, located 680 kb upstream. The risk allele of the most likely causal SNP, rs6927172, is correlated with both a higher frequency of interactions and increased expression of IL20RA, along with a stronger binding of both the NFκB transcription factor and chromatin marks characteristic of active enhancers in T-cells. CONCLUSIONS: Our results highlight the importance of gene assignment for translating GWAS findings into biologically meaningful mechanisms of disease and potential therapeutic targets; indeed, monoclonal antibody therapy targeting IL-20 is effective in the treatment of rheumatoid arthritis and psoriasis, both with strong GWAS associations to this region.

19 Article CARD14 mutations may predict response to antitumour necrosis factor-α therapy in psoriasis: a potential further step towards personalized medicine. 2016

Wu, K C P / Reynolds, N J. ·Dermatological Sciences, Institute of Cellular Medicine, University of Newcastle, Newcastle upon Tyne, NE2 4HH, U.K. ·Br J Dermatol · Pubmed #27484270.

ABSTRACT: -- No abstract --

20 Article Pregnancy Outcomes in the Tofacitinib Safety Databases for Rheumatoid Arthritis and Psoriasis. 2016

Clowse, Megan E B / Feldman, Steven R / Isaacs, John D / Kimball, Alexandra B / Strand, Vibeke / Warren, Richard B / Xibillé, Daniel / Chen, Yan / Frazier, Donald / Geier, Jamie / Proulx, James / Marren, Amy. ·Duke University School of Medicine, Durham, NC, USA. · Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, USA. · The NIHR Newcastle Biomedical Research Centre, Newcastle University and Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. · Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. · Division of Immunology/Rheumatology, Stanford University School of Medicine, Palo Alto, CA, USA. · Dermatology Centre, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. · Hospital General de Cuernavaca, Cuernavaca, Morelos, Mexico. · Pfizer Inc, 500 Arcola Rd, Collegeville, PA, 19426, USA. · Pfizer Inc, Groton, CT, USA. · Pfizer Inc, New York, NY, USA. · Pfizer Inc, 500 Arcola Rd, Collegeville, PA, 19426, USA. Amy.marren@pfizer.com. ·Drug Saf · Pubmed #27282428.

ABSTRACT: INTRODUCTION: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), and is being investigated for the treatment of psoriasis. Both conditions can present in women of child-bearing potential, but pregnancy was an exclusion and discontinuation criterion in tofacitinib randomized controlled trials (RCTs) because of the unknown effects of tofacitinib on mother and child. Tofacitinib is a small molecule that has the potential to cross the placenta. OBJECTIVE: The objective was to report outcomes of pregnancy cases identified through April 2014 from tofacitinib RA/psoriasis RCTs, RA post-approval non-interventional studies, and spontaneous adverse-event reporting. METHODS: Pregnancy outcomes were categorized as follows: healthy newborn, medical termination, fetal death, congenital malformation, spontaneous abortion, or pending/lost to follow-up. RESULTS: Out of 9815 patients, 1821 female patients of child-bearing age were enrolled in the RA/psoriasis RCTs; 47 women became pregnant, including 33 who received tofacitinib monotherapy, 13 who received combination therapy with methotrexate (RA patients only), and one patient whose therapy was still blinded. No fetal deaths were reported. One congenital pulmonary valve stenosis (monotherapy, n = 1), seven spontaneous abortions (monotherapy, n = 4; combination therapy, n = 3), and eight medical terminations (monotherapy, n = 4; combination therapy, n = 3; blinded therapy, n = 1) were identified. Remaining cases reported healthy newborns (n = 25) or were pending/lost to follow-up (n = 6). Forty-four cases of paternal exposure to tofacitinib were reported (monotherapy, n = 43; combination therapy, n = 1), including five spontaneous abortions (monotherapy, n = 4; combination therapy, n = 1), 23 healthy newborns, and 16 pending/lost to follow-up. CONCLUSIONS: The pregnancy outcomes reported in this small number of RA/psoriasis patients appear similar to those observed in the general population and in patients treated with biologic therapies for inflammatory diseases. However, definitive conclusions cannot be drawn, and pregnancy outcomes in patients receiving tofacitinib will continue to be monitored.

21 Article Regorafenib-Associated Vulvar Psoriasiform Skin Reaction: Case of the Month from the ISSVD Case Consultation Committee. 2016

Bourne, Emma-Lee / Day, Tania / Scurry, James. ·1Maternity and Gynaecology, John Hunter Hospital, New Lambton Heights, New South Wales, Australia; 2Faculty of Medicine and Health, University of Newcastle, Callaghan, NSW, Australia; and 3Pathology North, Hunter, New England, New Lambton, New South Wales, Australia. ·J Low Genit Tract Dis · Pubmed #27195780.

ABSTRACT: -- No abstract --

22 Article Kidney disease in moderate-to-severe psoriasis: a critical appraisal. 2016

Jabbar-Lopez, Z K / Weatherhead, S C / Reynolds, N J. ·Dermatological Sciences, Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, U.K. · Department of Dermatology, Royal Victoria Infirmary, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE1 4LP, U.K. ·Br J Dermatol · Pubmed #26871922.

ABSTRACT: AIM: Using a population-based cohort, Wan et al. examined the risk of moderate-to-advanced (stage 3-5) chronic kidney disease (CKD) in patients with psoriasis. SETTING AND DESIGN: A population-based cohort was constructed using The Health Improvement Network (THIN) database. THIN is an electronic primary healthcare records database containing routinely collected medical diagnosis and drug prescribing data on > 9 million patients in the U.K. Data were collected prospectively on 143 883 adults (aged 18-90 years) with psoriasis. Of these, 7354 had severe psoriasis, as defined by prescription codes for systemic medication or treatment codes for phototherapy. Patients with psoriasis were matched with up to five nonpsoriasis age- and practice-matched controls. Patients with a diagnosis of CKD before study entry were excluded. In addition, baseline data from the Incident Health Outcomes and Psoriasis Events (iHOPE) study, a cohort of 8731 primary care patients aged 25-64 years with psoriasis, was included. Psoriasis severity was categorized according to body surface area (BSA) involvement as estimated by general practitioners. A similar method using a patient-reported BSA assessment tool was previously validated by the same group. Patients were matched by age and practice with 10 nonpsoriasis controls. STUDY EXPOSURE: Psoriasis, identified on the basis of a recorded diagnostic code for psoriasis. OUTCOMES: Incident CKD was defined as the presence of a recorded diagnostic code consistent with moderate-to-advanced (stage 3-5) CKD or laboratory parameters consistent with the diagnosis (estimated glomerular filtration rate < 60 mL min(-1)  1·73 m(-2) ) during follow-up. Prevalent CKD (as defined above) in the cross-sectional data from the iHOPE study. RESULTS: The adjusted hazard ratios for incident CKD were 1·05 [95% confidence interval (CI) 1·02-1·07], 0·99 (95% CI 0·97-1·02) and 1·93 (95% CI 1·79-2·08) in the overall, mild and severe psoriasis groups, respectively. In the nested cross-sectional study (iHOPE) the adjusted prevalence odds ratios for CKD were 0·89 (95% CI 0·72-1·10), 1·36 (95% CI 1·06-1·74) and 1·58 (95% CI 1·07-2·34) in the mild, moderate and severe psoriasis groups, respectively. CONCLUSIONS: Moderate-to-severe psoriasis is associated with an increased risk of moderate-to-advanced CKD, independently of traditional risk factors.

23 Article Differential Drug Survival of Biologic Therapies for the Treatment of Psoriasis: A Prospective Observational Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR). 2015

Warren, Richard B / Smith, Catherine H / Yiu, Zenas Z N / Ashcroft, Darren M / Barker, Jonathan N W N / Burden, A David / Lunt, Mark / McElhone, Kathleen / Ormerod, Anthony D / Owen, Caroline M / Reynolds, Nick J / Griffiths, Christopher E M. ·Dermatology Centre, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. Electronic address: christopher.griffiths@manchester.ac.uk. · St John's Institute of Dermatology, 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. Electronic address: zenas.yiu@manchester.ac.uk. · Centre for Pharmacoepidemiology and Drug Safety, Manchester Pharmacy School, The University of Manchester, Manchester, UK. · Department of Dermatology, Western Infirmary, Glasgow, UK. · Arthritis Research UK Epidemiology Unit, The University of Manchester, Manchester, UK. · Division of Applied Medicine, University of Aberdeen, Foresterhill, Aberdeen, UK. · Department of Dermatology, East Lancashire Hospitals NHS Trust, Royal Blackburn Hospital, Blackburn, UK. · Dermatological Sciences, Institute of Cellular Medicine, Medical School, Newcastle University, and Department of Dermatology, Royal Victoria Infirmary, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. ·J Invest Dermatol · Pubmed #26053050.

ABSTRACT: Drug survival reflects a drug's effectiveness, safety, and tolerability. We assessed the drug survival of biologics used to treat psoriasis in a prospective national pharmacovigilance cohort (British Association of Dermatologists Biologic Interventions Register (BADBIR)). The survival rates of the first course of biologics for 3,523 biologic-naive patients with chronic plaque psoriasis were compared using survival analysis techniques and predictors of discontinuation analyzed using a multivariate Cox proportional hazards model. Data for patients on adalimumab (n=1,879), etanercept (n=1,098), infliximab (n=96), and ustekinumab (n=450) were available. The overall survival rate in the first year was 77%, falling to 53% in the third year. Multivariate analysis showed that female gender (hazard ratio (HR) 1.22; 95% confidence interval (CI): 1.09-1.37), being a current smoker (HR 1.19; 95% CI: 1.03-1.38), and a higher baseline dermatology life quality index (HR 1.01; 95% CI: 1.00-1.02) were predictors of discontinuation. Presence of psoriatic arthritis (HR 0.82; 95% CI: 0.71-0.96) was a predictor for drug survival. As compared with adalimumab, patients on etanercept (HR 1.63; 95% CI: 1.45-1.84) or infliximab (HR 1.56; 95% CI: 1.16-2.09) were more likely to discontinue therapy, whereas patients on ustekinumab were more likely to persist (HR 0.48; 95% CI: 0.37-0.62). After accounting for relevant covariates, ustekinumab had the highest first-course drug survival. The results of this study will aid clinical decision making when choosing biologic therapy for psoriasis patients.

24 Article Demographics and disease characteristics of patients with psoriasis enrolled in the British Association of Dermatologists Biologic Interventions Register. 2015

Iskandar, I Y K / Ashcroft, D M / Warren, R B / Yiu, Z Z N / McElhone, K / Lunt, M / Barker, J N W N / Burden, A D / Ormerod, A D / Reynolds, N J / Smith, C H / Griffiths, C E M. ·Centre for Pharmacoepidemiology and Drug Safety, Manchester Pharmacy School, The University of Manchester, Manchester, U.K. · Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, The University of Manchester, Barnes Building, Manchester, M6 8HD, U.K. · Arthritis Research U.K. Epidemiology Unit, The University of Manchester, Manchester, U.K. · St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, U.K. · Department of Dermatology, Western Infirmary, Glasgow, U.K. · Division of Applied Medicine, University of Aberdeen, Foresterhill, Aberdeen, U.K. · Dermatological Sciences, Institute of Cellular Medicine, Medical School, Royal Victoria Infirmary, Newcastle University, Newcastle upon Tyne, U.K. ·Br J Dermatol · Pubmed #25989336.

ABSTRACT: BACKGROUND: The British Association of Dermatologists Biologic Interventions Register (BADBIR) is a prospective, observational cohort designed to assess the long-term safety of biologic and conventional systemic therapies used for adults with moderate-to-severe psoriasis in the U.K. and Republic of Ireland. OBJECTIVES: To describe the demographics, disease severity and comorbidities of patients with psoriasis on enrolment into BADBIR, and to highlight differences in those commencing biologics compared with those on conventional systemic therapies. METHODS: Baseline data were collected from 151 dermatology departments in the U.K. and Republic of Ireland. Descriptive analysis was conducted. RESULTS: As of August 2014, 8399 patients were registered with BADBIR; 5065 (60%) received biologics, of whom 52·8% received adalimumab, 24·6% etanercept, 18·7% ustekinumab and 3·9% infliximab. In the comparator cohort 44·1% received methotrexate, 23·1% ciclosporin, 18·0% acitretin and 7·6% fumaric acid esters. Overall 4897 (58%) were male. Patients on biologics had a higher mean ± SD age and disease duration than patients on conventional systemic therapies (46·3 ± 12·7 vs. 44·3 ± 14·3 years and 23·0 ± 12·6 vs. 19·0 ± 13·4 years, respectively; both P < 0·001). Mean body mass index, Psoriasis Area and Severity Index and Dermatology Life Quality Index scores for patients on biologics were higher than for those on conventional systemic therapies (31·0 ± 7·2 vs. 30·1 ± 7·3 kg m(-2) ; 16·4 ± 8·3 vs. 15·5 ± 7·9 and 17·4 ± 7·5 vs. 15·0 ± 7·1, respectively; all P < 0·001). In total 71% of all patients had comorbidities and 47% had more than one comorbidity. The most frequent comorbidities were obesity (42·1%), hypertension (25·7%), depression (22·1%) and psoriatic arthritis (17·1%). CONCLUSIONS: BADBIR is an invaluable resource to study the safety and effectiveness of both biologic and conventional systemic therapies. Understanding differences in baseline characteristics between cohorts is crucial in undertaking future pharmacovigilance studies.

25 Article Young people's decisions about biologic therapies: who influences them and how? 2015

Hart, Ruth I / Foster, Helen E / McDonagh, Janet E / Thompson, Ben / Kay, Lesley / Myers, Andrea / Rapley, Tim. ·Institute of Health and Society, Newcastle University, Institute of Cellular Medicine, Newcastle University, Newcastle, School of Immunity and Infection, University of Birmingham, Birmingham, Musculoskeletal Services, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, and Rheumatology, Northumbria Healthcare NHS Foundation Trust, North Shields, UK ruth.hart@ncl.ac.uk. · Institute of Health and Society, Newcastle University, Institute of Cellular Medicine, Newcastle University, Newcastle, School of Immunity and Infection, University of Birmingham, Birmingham, Musculoskeletal Services, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, and Rheumatology, Northumbria Healthcare NHS Foundation Trust, North Shields, UK. ·Rheumatology (Oxford) · Pubmed #25661469.

ABSTRACT: OBJECTIVES: Young people with inflammatory arthritis can have severe disease warranting biologic therapy. They face complex treatment decisions, with profound consequences. This study aimed to explore the influence of individuals outside the care team (trusted others) on the treatment decisions made by young people, in particular their decisions about biologic therapies. METHODS: Young people (16-25 years of age) with inflammatory arthritis and experience of treatment decision making were recruited from three NHS Hospital Trusts. Twenty-five were interviewed, plus 11 trusted others identified by young people as being involved in their decision making, as well as 6 health professionals. The data were analysed using coding, memoing and mapping techniques and the findings were tested through a series of focus groups. RESULTS: Young people initially emphasized their decisional autonomy, typically describing people other than health professionals as limited in influence. However, discussions revealed the involvement--in deliberation and enactment--of a range of other people. This cast of trusted others was small and largely consistent; mothers played a particularly prominent role, providing cognitive, practical and emotional support. Members of the wider cast of trusted others were involved in more limited but still significant ways. CONCLUSION: Young people claim autonomy but other people enable this. The network of relationships in which they are embedded is distinctive and evolving. Mothers play a supporting role well into early adulthood; in contrast, partners are involved in far more limited ways. As such, the applicability of adult models of decision making is unclear. This must be taken into account if the support provided by professionals is to be optimally tailored to young people's needs.

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