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Psoriasis: HELP
Articles from Miscellaneous institutions in Seattle
Based on 11 articles published since 2010

These are the 11 published articles about Psoriasis that originated from Miscellaneous institutions in Seattle during 2010-2020.
+ Citations + Abstracts
1 Review The IL-20 Cytokine Family in Rheumatoid Arthritis and Spondyloarthritis. 2018

Kragstrup, Tue W / Andersen, Thomas / Heftdal, Line D / Hvid, Malene / Gerwien, Jens / Sivakumar, Pallavur / Taylor, Peter C / Senolt, Ladislav / Deleuran, Bent. ·Department of Biomedicine, Aarhus University, Aarhus, Denmark. · Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark. · Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. · Eli Lilly, Herlev, Denmark. · Immuno Oncology Translational Development, Celgene Corportation, Seattle, WA, United States. · Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom. · Institute of Rheumatology and Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czechia. ·Front Immunol · Pubmed #30319661.

ABSTRACT: This review describes the IL-20 family of cytokines in rheumatoid arthritis (RA) and spondyloartrhitits (SpA) including psoriatic arthritis. The IL-20 receptor (R) cytokines IL-19, IL-20, and IL-24 are produced in both the peripheral blood and the synovial joint and are induced by Toll-like receptor ligands and autoantibody-associated immune complexes in monocytes. IL-19 seems to have anti-inflammatory functions in arthritis. In contrast, IL-20 and IL-24 increase the production of proinflammatory molecules such as monocyte chemoattractant protein 1 and are associated with bone degradation and radiographic progression. IL-22 is also associated with progression of bone erosions. This suggests that the IL-22RA1 subunit shared by IL-20, IL-22, and IL-24 is important for bone homeostasis. In line with this, the IL-22RA1 has been found on preosteoclasts in early RA. IL-26 is produced in high amounts by myofibroblasts and IL-26 stimulation of monocytes is an important inducer of Th17 cells in RA. This indicates a role for IL-26 as an important factor in the interactions between resident synovial cells and infiltrating leukocytes. Clinical trials that investigate inhibitors of IL-20 (fletikumab) and IL-22 (fezakinumab) in psoriasis and RA have been terminated. Instead, it seems that the strategy for modulating the IL-20 cytokine family should take the overlap in cellular sources and effector mechanisms into account. The redundancy encourages inhibition of more than one cytokine or one of the shared receptors. All IL-20 family members utilize the Janus kinase signaling pathway and are therefore potentially inhibited by drugs targeting these enzymes. Effects and adverse effects in ongoing clinical trials with inhibitors of IL-22 and the IL-22RA1 subunit and recombinant IL-22 fusion proteins will possibly provide important information about the IL-20 subfamily of cytokines in the future.

2 Clinical Trial Safety and pharmacodynamics of dalazatide, a Kv1.3 channel inhibitor, in the treatment of plaque psoriasis: A randomized phase 1b trial. 2017

Tarcha, Eric J / Olsen, Chelsea M / Probst, Peter / Peckham, David / Muñoz-Elías, Ernesto J / Kruger, James G / Iadonato, Shawn P. ·Kineta Inc., Seattle, WA, United States of America. · Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, United States of America. ·PLoS One · Pubmed #28723914.

ABSTRACT: BACKGROUND: Dalazatide is a specific inhibitor of the Kv1.3 potassium channel. The expression and function of Kv1.3 channels are required for the function of chronically activated memory T cells, which have been shown to be key mediators of autoimmune diseases, including psoriasis. OBJECTIVE: The primary objective was to evaluate the safety of repeat doses of dalazatide in adult patients with mild-to-moderate plaque psoriasis. Secondary objectives were to evaluate clinical proof of concept and the effects of dalazatide on mediators of inflammation in the blood and on chronically activated memory T cell populations. METHODS: Patients (n = 24) were randomized 5:5:2 to receive dalazatide at 30 mcg/dose, 60 mcg/dose, or placebo twice weekly by subcutaneous injection (9 doses total). Safety was assessed on the basis of physical and neurological examination and laboratory testing. Clinical assessments included body-surface area affected, Psoriasis Area and Severity Index (PASI), and investigator and patient questionnaires. RESULTS: The most common adverse events were temporary mild (Grade 1) hypoesthesia (n = 20; 75% placebo, 85% dalazatide) and paresthesia (n = 15; 25% placebo, 70% dalazatide) involving the hands, feet, or perioral area. Nine of 10 patients in the 60 mcg/dose group had a reduction in their PASI score between baseline and Day 32, and the mean reduction in PASI score was significant in this group (P < 0.01). Dalazatide treatment reduced the plasma levels of multiple inflammation markers and reduced the expression of T cell activation markers on peripheral blood memory T cells. LIMITATIONS: The study was small and drug treatment was for a short duration (4 weeks). CONCLUSION: This study indicates that dalazatide is generally well tolerated and can improve psoriatic skin lesions by modulating T cell surface and activation marker expression and inhibiting mediators of inflammation in the blood. Larger studies of longer duration are warranted.

3 Clinical Trial Single-joint outcome measures: preliminary validation of patient-reported outcomes and physical examination. 2010

Heald, Alison E / Fudman, Edward J / Anklesaria, Pervin / Mease, Philip J / Anonymous1890653. ·Targeted Genetics Corporation, Seattle, Washington, USA. ·J Rheumatol · Pubmed #20231202.

ABSTRACT: OBJECTIVE: To assess the validity, responsiveness, and reliability of single-joint outcome measures for determining target joint (TJ) response in patients with inflammatory arthritis. METHODS: Patient-reported outcomes (PRO), consisting of responses to single questions about TJ global status on a 100-mm visual analog scale (VAS; TJ global score), function on a 100-mm VAS (TJ function score), and pain on a 5-point Likert scale (TJ pain score) were piloted in 66 inflammatory arthritis subjects in a phase 1/2 clinical study of an intraarticular gene transfer agent and compared to physical examination measures (TJ swelling, TJ tenderness) and validated function questionnaires (Disabilities of the Arm, Shoulder and Hand scale, Rheumatoid Arthritis Outcome Score, and the Health Assessment Questionnaire). Construct validity was assessed by evaluating the correlation between the single-joint outcome measures and validated function questionnaires using Spearman's rank correlation. Responsiveness or sensitivity to change was assessed through calculating effect size and standardized response means (SRM). Reliability of physical examination measures was assessed by determining interobserver agreement. RESULTS: The single-joint PRO were highly correlated with each other and correlated well with validated functional measures. The TJ global score exhibited modest effect size and modest SRM that correlated well with the patient's assessment of response on a 100-mm VAS. Physical examination measures exhibited high interrater reliability, but correlated less well with validated functional measures and the patient's assessment of response. CONCLUSION: Single-joint PRO, particularly the TJ global score, are simple to administer and demonstrate construct validity and responsiveness in patients with inflammatory arthritis. (ClinicalTrials.gov identifier NCT00126724).

4 Article Apremilast for the treatment of moderate-to-severe palmoplantar psoriasis: results from a double-blind, placebo-controlled, randomized study. 2018

Bissonnette, R / Haydey, R / Rosoph, L A / Lynde, C W / Bukhalo, M / Fowler, J F / Delorme, I / Gagné-Henley, A / Gooderham, M / Poulin, Y / Barber, K / Jenkin, P / Landells, I / Pariser, D M. ·Innovaderm Research, Montreal, QC, Canada. · Winnipeg Clinic, Winnipeg, MB, Canada. · North Bay Dermatology Centre, North Bay, ON, Canada. · Lynderm Research, Markham, ON, Canada. · Altman Dermatology Associates, Arlington Heights, IL, USA. · Dermatology Specialists Research, Louisville, KY, USA. · Dr Isabelle Delorme Inc., Drummondville, QC, Canada. · Dre Angélique Gagné-Henley MD Inc., Saint-Jérôme, QC, Canada. · Dr. Melinda Gooderham SKiN Centre for Dermatology, Peterborough, ON, Canada. · Centre de Recherche Dermatologique du Québec Métropolitain, Québec, QC, Canada. · Kirk Barber Research, Calgary, AB, Canada. · Dermatology Associates, Seattle, WA, USA. · Nexus Clinical Research, St. John's, NL, Canada. · Department of Dermatology, Eastern Virginia Medical School and Virginia Clinical Research Inc., Norfolk, VA, USA. ·J Eur Acad Dermatol Venereol · Pubmed #29055155.

ABSTRACT: BACKGROUND: Palmoplantar psoriasis is a variant of psoriasis vulgaris which can severely impair quality of life. OBJECTIVES: The main objectives of this double-blind, placebo-controlled, randomized study were to assess the efficacy and impact on quality of life and work productivity of apremilast for the treatment of moderate-to-severe palmoplantar psoriasis. METHODS: A total of 100 patients with moderate-to-severe palmoplantar psoriasis were randomized to either apremilast 30 mg bid or placebo for 16 weeks. At Week 16, all patients received apremilast 30 mg bid until Week 32. The primary endpoint was the proportion of patients who achieved a Palmoplantar Psoriasis Physician Global Assessment (PPPGA) of 0/1 at Week 16. RESULTS: There was no significant difference in the proportion of patients who achieved a PPPGA of 0/1 at Week 16 between patients randomized to apremilast (14%) and placebo (4%; P = 0.1595). After 32 weeks of treatment with apremilast, 24% of patients achieved a PPGA of 0/1. In addition, apremilast was superior to placebo in achieving Palmoplantar Psoriasis Area Severity Index (PPPASI) 75 (apremilast: 22%; placebo: 8%; P = 0.0499), in improving PPPASI (apremilast: -7.4 ± 7.1; placebo: -3.6 ± 5.9; P = 0.0167), Dermatology Life Quality Index score (apremilast: -4.3 ± 5.1; placebo: -0.8 ± 4.5; P = 0.0004) and in reducing activity impairment (apremilast: -11.0 ± 22.3; placebo: 2.5 ± 25.5; P = 0.0063). CONCLUSION: Despite the absence of a significant difference between apremilast and placebo in proportion of patients achieving a PPPGA of 0/1, the presence of significant differences observed for several secondary endpoints suggests that apremilast may have a role in the treatment of moderate-to-severe palmoplantar psoriasis.

5 Article Dermatologic Conditions and Risk of Suicide: A Case-Control Study. 2018

Prabhakar, Deepak / Peterson, Edward L / Hu, Yong / Rossom, Rebecca C / Lynch, Frances L / Lu, Christine Y / Waitzfelder, Beth E / Owen-Smith, Ashli A / Williams, L Keoki / Beck, Arne / Simon, Gregory E / Ahmedani, Brian K. ·Behavioral Health Services, Henry Ford Health System, Detroit, MI. Electronic address: dprabha1@hfhs.org. · Center for Health Policy & Health Services Research, Henry Ford Health System, Detroit, MI. · HealthPartners Institute, Bloomington, MN. · Center for Health Research, Kaiser Permanente Northwest, Portland, OR. · Harvard Pilgrim Health Care, Wellesley, MA; Department of Population Medicine, Harvard Medical School, Boston, MA, USA. · Kaiser Permanente, Portland, OR. · Georgia State University, Atlanta, GA. · Kaiser Permanente Washington Health Research Institute, Seattle, WA. ·Psychosomatics · Pubmed #28890116.

ABSTRACT: BACKGROUND: Patients diagnosed with skin conditions have a higher risk of comorbid psychiatric conditions and suicide-related outcomes such as suicidal ideations and behaviors. There is paucity of evidence in the US general population about the risk of suicide death in patients with dermatologic conditions. METHODS: We conducted a retrospective case-control study to investigate the risk of suicide death in patients receiving care for dermatologic conditions. This study involved 8 US health systems. A total of 2674 individuals who died by suicide (cases) were matched with 267,400 general population control individuals. RESULTS: After adjusting for age, sex, and any mental health or substance use condition, we did not find an association between death by suicide and any skin condition including conditions where clinicians are generally concerned about the risk such as acne (adjusted odds ratio [aOR] = 1.04, p = 0.814), atopic dermatitis (aOR = 0.77, p = 0.28), and psoriasis (aOR = 0.91, p = 0.64). CONCLUSION: This case-control study provides no evidence of increased risk of death by suicide in individuals with major skin disorders in the US general population.

6 Article The content validity of the PSS in patients with plaque psoriasis. 2017

Rentz, A M / Skalicky, A M / Burslem, K / Becker, K / Kaschinski, D / Esser, D / Revicki, D A. ·Evidera, 7101 Wisconsin Avenue, Suite 1400, Bethesda, MD 20814 USA. · Evidera, Seattle, WA USA. · 3Boehringer Ingelheim GmbH, Ingelheim am Rhein, Germany. · 0000 0001 2171 7500 · grid.420061.1 ·J Patient Rep Outcomes · Pubmed #29757301.

ABSTRACT: Background: The primary objective of this study was to evaluate the content validity of the Psoriasis Symptom Scale (PSS), with a specific focus on understanding of the content of the PRO measure by conducting one-on-one interviews with patients with moderate to severe plaque psoriasis. This was a cross-sectional, qualitative study conducted with 20 patients with plaque psoriasis who participated in in-person, one-on-one interviews. Participants were asked to describe their psoriasis symptoms, completed the PSS, and were cognitively debriefed on its content. Interviews were conducted in two separate rounds. Following Round 1, the study data were examined to determine if modifications to the PSS were required. All interviews were audio-recorded and transcribed. Sociodemographic and clinical data were collected for sample descriptive purposes. Results: The 20 study participants had a mean age of 50.2 ± 12.0 years (range: 25.0-73.0), and 55% were female. Thirty-five percent of the sample reported their psoriasis severity as moderate or severe. The average time since diagnosis of plaque psoriasis was almost 18 years, ranging from less than one to over 38 years. The most frequently reported symptoms and signs during the concept elicitation portion of the interviews included redness ( Conclusion: The evidence gained in this study provided support for the content validity of the PSS for use as clinical trial endpoint among patients with plaque psoriasis. This study found that the symptoms included in the PSS are important to and well-understood by patients with plaque psoriasis. The PSS is appropriate for inclusion in future studies designed to measure the effect of treatment on psoriasis-related symptoms.

7 Article Clinically resolved psoriatic lesions contain psoriasis-specific IL-17-producing αβ T cell clones. 2017

Matos, Tiago R / O'Malley, John T / Lowry, Elizabeth L / Hamm, David / Kirsch, Ilan R / Robins, Harlan S / Kupper, Thomas S / Krueger, James G / Clark, Rachael A. ·Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. · Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal. · Academic Medical Center, Department of Dermatology, University of Amsterdam, Amsterdam, The Netherlands. · Adaptive Biotechnologies, Seattle, Washington, USA. · Department of Dermatology, Rockefeller University, New York, New York, USA. ·J Clin Invest · Pubmed #28945199.

ABSTRACT: In psoriasis, an IL-17-mediated inflammatory skin disease, skin lesions resolve with therapy, but often recur in the same locations when therapy is discontinued. We propose that residual T cell populations in resolved psoriatic lesions represent the pathogenic T cells of origin in this disease. Utilizing high-throughput screening (HTS) of the T cell receptor (TCR) and immunostaining, we found that clinically resolved psoriatic lesions contained oligoclonal populations of T cells that produced IL-17A in both resolved and active psoriatic lesions. Putative pathogenic clones preferentially utilized particular Vβ and Vα subfamilies. We identified 15 TCRβ and 4 TCRα antigen receptor sequences shared between psoriasis patients and not observed in healthy controls or other inflammatory skin conditions. To address the relative roles of αβ versus γδ T cells in psoriasis, we carried out TCR/δ HTS. These studies demonstrated that the majority of T cells in psoriasis and healthy skin are αβ T cells. γδ T cells made up 1% of T cells in active psoriasis, less than 1% in resolved psoriatic lesions, and less than 2% in healthy skin. All of the 70 most frequent putative pathogenic T cell clones were αβ T cells. In summary, IL-17-producing αβ T cell clones with psoriasis-specific antigen receptors exist in clinically resolved psoriatic skin lesions. These cells likely represent the disease-initiating pathogenic T cells in psoriasis, suggesting that lasting control of this disease will require suppression of these resident T cell populations.

8 Article Deep Sequencing of the T-cell Receptor Repertoire Demonstrates Polyclonal T-cell Infiltrates in Psoriasis. 2015

Harden, Jamie L / Hamm, David / Gulati, Nicholas / Lowes, Michelle A / Krueger, James G. ·Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA. · Adaptive Biotechnologies, Seattle, WA, USA. · Division of Dermatology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA. ·F1000Res · Pubmed #26594339.

ABSTRACT: It is well known that infiltration of pathogenic T-cells plays an important role in psoriasis pathogenesis. However, the antigen specificity of these activated T-cells is relatively unknown. Previous studies using T-cell receptor polymerase chain reaction technology (TCR-PCR) have suggested there are expanded T-cell receptor (TCR) clones in psoriatic skin, suggesting a response to an unknown psoriatic antigen. Here we describe the results of high-throughput deep sequencing of the entire αβ- and γδ- TCR repertoire in normal healthy skin and psoriatic lesional and non-lesional skin. From this study, we were able to determine that there is a significant increase in the abundance of unique β- and γ- TCR sequences in psoriatic lesional skin compared to non-lesional and normal skin, and that the entire T-cell repertoire in psoriasis is polyclonal, with similar diversity to normal and non-lesional skin. Comparison of the αβ- and γδ- TCR repertoire in paired non-lesional and lesional samples showed many common clones within a patient, and these close were often equally abundant in non-lesional and lesional skin, again suggesting a diverse T-cell repertoire. Although there were similar (and low) amounts of shared β-chain sequences between different patient samples, there was significantly increased sequence sharing of the γ-chain in psoriatic skin from different individuals compared to those without psoriasis. This suggests that although the T-cell response in psoriasis is highly polyclonal, particular γδ- T-cell subsets may be associated with this disease. Overall, our findings present the feasibility of this technology to determine the entire αβ- and γδ- T-cell repertoire in skin, and that psoriasis contains polyclonal and diverse αβ- and γδ- T-cell populations.

9 Article AZ17: a new bispecific drug targeting IL-6 and IL-23 with potential clinical use--improves psoriasis in a human xenograft transplantation model. 2015

Stenderup, Karin / Rosada, Cecilia / Shanebeck, Kurt / Brady, William / Van Brunt, Michael P / King, Gordon / Marelli, Marcello / Slagle, Paul / Xu, Hengyu / Nairn, Natalie W / Johnson, Jeffrey / Wang, Aijun A / Li, Gary / Thornton, Kenneth C / Dam, Tomas N / Grabstein, Kenneth H. ·Research Centre S, Department of Dermatology, Aarhus University Hospital, P.P. Oerumsgade 11, bldg. 15b, DK-8000 Aarhus C, Denmark karin.stenderup@clin.au.dk. · Research Centre S, Department of Dermatology, Aarhus University Hospital, P.P. Oerumsgade 11, bldg. 15b, DK-8000 Aarhus C, Denmark. · Allozyne, Seattle, WA 98102, USA. · Department of Dermatology, Roskilde Hospital, DK-4000 Roskilde, Denmark. ·Protein Eng Des Sel · Pubmed #26271488.

ABSTRACT: Targeting more than one molecule in multifactorial diseases involving several disease mediators may provide improved therapeutic efficacy. Psoriasis is a multifactorial disease in which interleukin (IL)-6 and IL-23 are important disease mediators because they facilitate development of Th17 cells; widely accepted to be associated with psoriasis. To meet the need for new therapeutics, we aimed to create a clinically relevant bispecific drug, by combining the inhibitory properties of anti-IL-6 and anti-IL-23 antibodies, exhibiting high affinity, high stability and the ability to be produced in high yield. The bispecific molecule AZ17 was created by combining high affinity binding domains originating from monoclonal antibodies targeting human IL-6 and IL-23. To allow for high and efficient production, AZ17 was assembled by site-specific bioconjugation from two individual single chain fragment variables that were synthesized separately in Escherichia coli. To improve stability and extend pharmacokinetics, a flexible poly-ethylene glycol molecule was used as linker. In preclinical psoriasis models, AZ17 reduced IL-23-induced ear inflammation and improved psoriasis in a xenograft transplantation model where psoriasis skin is transplanted onto immune-deficient mice. The data presented here suggest AZ17 to be a promising drug candidate in psoriasis and other inflammatory diseases associated with Th17 cell development.

10 Article The experience of pain and redness in patients with moderate to severe plaque psoriasis. 2015

Martin, Mona L / Gordon, Kenneth / Pinto, Lionel / Bushnell, Donald M / Chau, Dina / Viswanathan, Hema N. ·a Health Research Associates , Seattle , WA , USA . · b Feinberg School of Medicine, Northwestern University , Chicago , IL , USA , and. · c Amgen Inc. , Thousand Oaks , CA , USA. ·J Dermatolog Treat · Pubmed #25822169.

ABSTRACT: INTRODUCTION: The Psoriasis Symptom Inventory is a patient-reported outcome instrument that assesses severity of psoriasis signs and symptoms. In early qualitative research, patients reported pain related to psoriasis skin lesions and redness of affected areas of skin as key symptoms. METHODS: Individual concept elicitation interviews and cognitive interviews were conducted in adults with moderate to severe plaque psoriasis. Interviews were audio-recorded and transcribed. Concepts were identified, coded and grouped by similar content using Atlas.ti software. Results were evaluated using qualitative research methods. RESULTS: Of 30 patients recruited, 20 patients participated in concept elicitation interviews and 10 participated in cognitive interviews. Concept codes for skin pain and descriptions of color comprised 11% and 15%, respectively, of all symptom-related expressions. Of 90 pain-related expressions, 22 were about pain related to unconscious scratching and 68 were about pain from the psoriasis lesions. Of 199 color-related expressions, 72 were about red or reddish lesion color. Patients with darker skin tones were found to interpret redness consistently. DISCUSSION: These results provide further support to content validity of pain and redness concepts in the Psoriasis Symptom Inventory. CONCLUSIONS: Symptoms of skin pain and redness are highly relevant to patients with psoriasis.

11 Article Early development and qualitative evidence of content validity for the Psoriasis Symptom Inventory (PSI), a patient-reported outcome measure of psoriasis symptom severity. 2013

Martin, Mona L / McCarrier, Kelly P / Chiou, Chiun-Fang / Gordon, Kenneth / Kimball, Alexa B / Van Voorhees, Abby S / Gottlieb, Alice B / Huang, Xingyue / Globe, Denise / Chau, Dina / Viswanathan, Hema N / Kricorian, Gregory. ·Health Research Associates, Seattle, WA, USA. martin@hrainc.net ·J Dermatolog Treat · Pubmed #23249143.

ABSTRACT: OBJECTIVE: To develop and assess content validity of the Psoriasis Symptom Inventory (PSI), a patient-reported outcome (PRO) measure of psoriasis symptoms. METHODS: Following initial literature exploration and input from experts, concept elicitation was conducted in two rounds (focus groups and individual interviews) with 59 subjects with mild to severe psoriasis. Transcripts were coded to identify symptom concepts and develop a conceptual framework using ATLAS.ti software. Qualitative content analysis and clinical expert input supported item generation and development of a draft measure. Two rounds of face-to-face cognitive interviews with 40 subjects with moderate to severe psoriasis were conducted to test subject comprehension and content coverage. RESULTS: Concepts of itching, scaling, flaking, tearing/cracking, burning, stinging, pain, bleeding and color of appearance were the most common symptom-related expressions. Saturation of concept was demonstrated. Severity was identified as the most meaningful attribute of psoriasis symptoms. A final 8-item measure was developed to assess patient-perceived symptom severity for itch, pain, burning, stinging, cracking, scaling, flaking and redness. Twenty-four-hour recall and 7-day recall versions were prepared for future quantitative assessment of measurement properties. CONCLUSIONS: The PSI is a short, low burden, patient-reported measure of psoriasis symptom severity with documented evidence of content validity.