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Psoriasis: HELP
Articles from Wisconsin
Based on 42 articles published since 2008
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These are the 42 published articles about Psoriasis that originated from Wisconsin during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics. 2019

Menter, Alan / Strober, Bruce E / Kaplan, Daniel H / Kivelevitch, Dario / Prater, Elizabeth Farley / Stoff, Benjamin / Armstrong, April W / Connor, Cody / Cordoro, Kelly M / Davis, Dawn M R / Elewski, Boni E / Gelfand, Joel M / Gordon, Kenneth B / Gottlieb, Alice B / Kavanaugh, Arthur / Kiselica, Matthew / Korman, Neil J / Kroshinsky, Daniela / Lebwohl, Mark / Leonardi, Craig L / Lichten, Jason / Lim, Henry W / Mehta, Nehal N / Paller, Amy S / Parra, Sylvia L / Pathy, Arun L / Rupani, Reena N / Siegel, Michael / Wong, Emily B / Wu, Jashin J / Hariharan, Vidhya / Elmets, Craig A. ·Baylor Scott and White, Dallas, Texas. · University of Connecticut, Farmington, Connecticut; Probity Medical Research, Waterloo, Ontario, Canada. · University of Pittsburgh, Pittsburgh, Pennsylvania. · University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. · Emory University School of Medicine, Atlanta, Georgia. · University of Southern California, Los Angeles, San Francisco. · University of Alabama, Birmingham, Alabama. · University of California, San Francisco School of Medicine, Department of Dermatology, San Francisco, California. · Mayo Clinic, Rochester, Minnesota. · University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. · Medical College of Wisconsin, Milwaukee, Wisconsin. · Department of Dermatology, Icahn School of Medicine at Mt. Sinai, New York. · University of California San Diego, San Diego, California. · National Psoriasis Foundation, Portland, Oregon. · University Hospitals Cleveland Medical Center, Cleveland, Ohio. · Massachusetts General Hospital, Boston, Massachusetts. · Central Dermatology, St. Louis, Missouri. · Department of Dermatology, Henry Ford Hospital, Detroit, Michigan. · National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. · Northwestern University Feinberg School of Medicine, Chicago, Illinois. · Dermatology and Skin Surgery, Sumter, South Carolina. · Colorado Permanente Medical Group, Centennial, Colorado. · San Antonio Uniformed Services Health Education Consortium, Joint-Base San Antonio. · Dermatology Research and Education Foundation, Irvine, California. · American Academy of Dermatology, Rosemont, Illinois. Electronic address: vhariharan@aad.org. ·J Am Acad Dermatol · Pubmed #30772098.

ABSTRACT: Psoriasis is a chronic, inflammatory multisystem disease that affects up to 3.2% of the US population. This guideline addresses important clinical questions that arise in psoriasis management and care, providing recommendations based on the available evidence. The treatment of psoriasis with biologic agents will be reviewed, emphasizing treatment recommendations and the role of the dermatologist in monitoring and educating patients regarding benefits as well as associated risks.

2 Guideline Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities. 2019

Elmets, Craig A / Leonardi, Craig L / Davis, Dawn M R / Gelfand, Joel M / Lichten, Jason / Mehta, Nehal N / Armstrong, April W / Connor, Cody / Cordoro, Kelly M / Elewski, Boni E / Gordon, Kenneth B / Gottlieb, Alice B / Kaplan, Daniel H / Kavanaugh, Arthur / Kivelevitch, Dario / Kiselica, Matthew / Korman, Neil J / Kroshinsky, Daniela / Lebwohl, Mark / Lim, Henry W / Paller, Amy S / Parra, Sylvia L / Pathy, Arun L / Prater, Elizabeth Farley / Rupani, Reena / Siegel, Michael / Stoff, Benjamin / Strober, Bruce E / Wong, Emily B / Wu, Jashin J / Hariharan, Vidhya / Menter, Alan. ·University of Alabama, Birmingham, Alabama. · Central Dermatology, St. Louis, Missouri. · Mayo Clinic, Rochester, Minnesota. · University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. · National Psoriasis Foundation, Portland, Oregon. · National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland. · University of Southern California, Los Angeles, California. · Department of Dermatology, University of California San Francisco School of MedicineSan Francisco, California. · Medical College of Wisconsin, Milwaukee, Wisconsin. · Department of Dermatology, Icahn School of Medicine at Mt. Sinai, New York, New York. · University of Pittsburgh, Pennsylvania. · University of California San Diego, San Diego, California. · Baylor Scott and White, Dallas, Texas. · University Hospitals Cleveland Medical Center, Cleveland, Ohio. · Massachusetts General Hospital, Boston, Massachusetts. · Department of Dermatology, Henry Ford Hospital, Detroit, Michigan. · Northwestern University Feinberg School of Medicine, Chicago, Illinois. · Dermatology and Skin Surgery, Sumter, South Carolina. · Colorado Permanente Medical Group, Centennial, Colorado. · University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. · Icahn School of Medicine at Mount Sinai, New York, New York. · Emory University School of Medicine, Atlanta, Georgia. · University of Connecticut, Farmington, Connecticut; Probity Medical Research, Waterloo, Canada. · San Antonio Uniformed Services Health Education Consortium, Joint-Base San Antonio, Texas. · Dermatology Research and Education Foundation, Irvine, California. · American Academy of Dermatology, Rosemont, Illinois. Electronic address: vhariharan@aad.org. ·J Am Acad Dermatol · Pubmed #30772097.

ABSTRACT: Psoriasis is a chronic, inflammatory, multisystem disease that affects up to 3.2% of the US population. This guideline addresses important clinical questions that arise in psoriasis management and care, providing recommendations on the basis of available evidence.

3 Editorial Advancing paediatric psoriasis treatment options for children. 2017

Tollefson, M / Siegel, D. ·Mayo Clinic, Rochester, MN, U.S.A. · Medical College of Wisconsin, Milwaukee, WI, U.S.A. ·Br J Dermatol · Pubmed #29313933.

ABSTRACT: -- No abstract --

4 Review Ocular features of the HLA-B27-positive seronegative spondyloarthropathies. 2018

Jhaj, Gurdeep / Kopplin, Laura J. ·Department of Ophthalmology & Visual Sciences, Medical College of Wisconsin Eye Institute, Milwaukee, Wisconsin, USA. ·Curr Opin Ophthalmol · Pubmed #30148724.

ABSTRACT: PURPOSE OF REVIEW: The seronegative spondyloarthropathies are a closely related group of inflammatory diseases that include ankylosing spondylitis, psoriatic arthritis, reactive arthritis, enteropathic arthritis, inflammatory bowel disease and undifferentiated spondyloarthritis. This review focuses on the spectrum of ocular manifestations associated with these diseases and the current approaches in treating these ocular manifestations. It also highlights the role ophthalmologists can play in identifying and appropriately treating human leukocyte antigen B27 (HLA-B27) associated uveitis and the associated spondyloarthropathies in order to limit ocular and systemic morbidity. RECENT FINDINGS: Evolving treatment paradigms for the seronegative spondyloarthropathies should direct the choice in therapeutic agent for difficult to control associated uveitis. Biologic therapies, particularly tumor necrosis factor inhibitors, are playing an increasing role in the treatment. SUMMARY: Acute anterior uveitis is the most common ocular manifestation in HLA-B27 positive seronegative spondyloarthropathies. Suspicion for HLA-B27 associated uveitis should prompt a careful clinical history and rheumatologic referral if symptoms of an inflammatory arthropathy are present. Therapy is tailored based on severity of ocular and systemic manifestations with interventions from topical corticosteroids to immunomodulating agents available in treating these diseases.

5 Review Role of sebaceous glands in inflammatory dermatoses. 2015

Shi, Vivian Y / Leo, Michael / Hassoun, Lauren / Chahal, Dev S / Maibach, Howard I / Sivamani, Raja K. ·Department of Dermatology, University of California, Davis, California. · School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin. · School of Medicine, University of California, Davis, California. · David Geffen School of Medicine, University of California, Los Angeles, California. · Department of Dermatology, University of California, San Francisco, California. · Department of Dermatology, University of California, Davis, California. Electronic address: rksivamani@ucdavis.edu. ·J Am Acad Dermatol · Pubmed #26386632.

ABSTRACT: Skin is an important interface between the host and its environment. Inflammatory dermatoses often have disrupted skin barrier function, rendering patients more susceptible to allergenic triggers leading to an exaggerated immune response. The skin surface lipid film, an important component of the skin barrier, comprises a mixture of keratinocyte and sebaceous gland-derived lipids. Recent evidence demonstrated that defective keratinocyte lipid synthesis predisposes for the development of atopic dermatitis. However, the important role of sebaceous gland-derived lipids in skin inflammatory diseases may be underrecognized. This overview focuses on the importance of the contribution of sebaceous glands to barrier function. Sebaceous gland alteration may play a role in the pathogenesis of common skin diseases including acne vulgaris, atopic dermatitis, psoriasis, rosacea, and seborrheic dermatitis.

6 Review Chemokine receptors in the pathogenesis and therapy of psoriasis. 2012

Mabuchi, Tomotaka / Chang, Timothy W / Quinter, Suzanne / Hwang, Sam T. ·Department of Dermatology, Medical College of Wisconsin, WI, USA. mabuchi@is.icc.u-tokai.ac.jp ·J Dermatol Sci · Pubmed #22177422.

ABSTRACT: Chemokine receptors are G-protein-coupled, seven-transmembrane-spanning surface receptors that play key roles in cell trafficking, cell motility, and survival. These receptors are activated by small molecular weight chemotactic cytokines called chemokines. Chemokine receptors and their corresponding chemokine ligands play roles in the migration and localization of normal T cells (and other cells) during physiological responses in inflamed or infected skin. In psoriasis, the chemokine receptor CCR6 is expressed on the Th17 cells and γδ T cells, which produce a variety of cytokines (IL17 and IL22 among others), that play a role in the immunological activation. CCR6 and its ligand, CCL20, are highly expressed in psoriatic skin lesion and CCR6 is essential for the development of the psoriasiform phenotype following IL23 injection in mouse skin. In this review, we focus on the roles of chemokine receptors, particularly of CCR6, in the pathogenesis of psoriasis and discuss chemokine receptors as novel therapeutic targets for psoriasis.

7 Review Psoriatic arthritis: update on pathophysiology, assessment and management. 2011

Mease, Philip J. ·Seattle Rheumatology Associates, 1101 Madison St Ste 1000, Seattle, WA 98104, USA. pmease@nwlink.com ·Ann Rheum Dis · Pubmed #21339225.

ABSTRACT: Psoriatic arthritis (PsA) is classified as a spondyloarthropathy and characterised by synovitis, enthesitis, dactylitis and spondylitis usually manifesting as skin and nail psoriasis. Our understanding about the PsA disease state, its genetics, pathophysiology and comorbidities, as well as the ability to assess and treat the disease, has advanced as a result of significant collaborative efforts by rheumatologists and dermatologists in the development of classification criteria, outcome measures to assess the various clinical domains, and treatment trials with agents also used for diseases such as rheumatoid arthritis (RA) and psoriasis. Biological agents, especially the antitumour necrosis factors, have demonstrated significant efficacy and reasonable safety in all clinical domains of the disease, resulting in amelioration of clinical symptoms, inhibition of structural damage and improvement of function and quality of life. Although there is considerable overlap with RA, there are some differences in pathophysiology and approach to assessment and management that are important to consider. This paper reviews these subjects, with an emphasis on recent data.

8 Review The importance of stereochemistry on the actions of vitamin D. 2011

Chiellini, G / DeLuca, Hector F. ·Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706-1544, USA. ·Curr Top Med Chem · Pubmed #21291397.

ABSTRACT: The seco-steroid hormone 1α,25-dihydroxyvitamin D(3) [1α,25(OH)(2)D(3)] is the most potent natural metabolite of vitamin D(3) and regulates primarily calcium and phosphate homeostasis, but also as a regulator of specific differentiation and of the immune system. Most, if not all, of the biological actions of 1α,25(OH)(2)D(3) are mediated through its specific receptor, the vitamin D receptor (VDR), which is a member of the nuclear receptor superfamily acting as a ligand-dependent transcription factor with coactivators. 1α,25(OH)(2)D(3) has significant therapeutic potential in the treatment of osteoporosis, rickets, secondary hyperparathyroidism, psoriasis, and renal osteodystrophy. However, the use of 1α,25(OH)(2)D(3) itself is limited because it induces significant hypercalcemia. Vitamin D is a highly flexible molecule and a very large number of analogs have been synthesized by industry and academia in an attempt to provide beneficial therapeutic agents with low calcemic activity. Chemical modifications of every portion of the vitamin D(3) molecule (the A, C, and D rings, the 17β-aliphatic side chain, and the 5,6,7,8-diene moiety) have been reported, with the most of the interesting analogs resulting from a combination of several modifications. The three-dimensional structure of both rat and human VDR-LBD have provided significant information for our understanding of the structure-function relationship (SFR) of vitamin D and some synthetic analogs. In this review, we focus on the current understanding of the relationship between selected stereochemical modifications of key structural components (i.e. A-ring, CD-ring and Side-chain) of the 1α,25(OH)(2)D(3) molecule and their effect on biological potency and selectivity. Based on current information, suggestions for the structure-based design of therapeutically valuable vitamin D analogs will conclude the review.

9 Review Congenital psoriasis: case report and literature review. 2008

Lehman, Julia S / Rahil, Anudeep K. ·University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA. lehman.julia@yahoo.com ·Pediatr Dermatol · Pubmed #18577037.

ABSTRACT: While childhood psoriasis is fairly common, congenital psoriasis appears to be rare and has not been well characterized. We present a patient with histologically confirmed congenital psoriasis. By reviewing the literature, we aim to both define this disease and compare it to infantile and childhood psoriasis. Electronic searches found articles reporting patients with biopsy-proven congenital psoriasis. We recorded clinical features, such as family history, anatomic involvement, and disease severity. We compared these data with previous descriptions of infantile and childhood psoriasis. We included nine patients with congenital psoriasis in our analysis. No patient had a first-degree family history of psoriasis. While the face, scalp, chest, and trunk were frequently involved, the buttocks generally were spared. Several patients had persistent disease despite therapy. In this series, congenital psoriasis differed from infantile and childhood psoriasis in several respects. Specifically, congenital psoriasis was associated with a lower prevalence of relevant family history, which could increase over time, and a different pattern of anatomic involvement, which may reflect exposure to age-associated environmental factors. Although several patients with congenital psoriasis had severe disease, this likely represents publication bias. Additional reports of congenital psoriasis with extended follow-up are needed to better characterize this condition.

10 Clinical Trial Phase 2 Trial of Selective Tyrosine Kinase 2 Inhibition in Psoriasis. 2018

Papp, Kim / Gordon, Kenneth / Thaçi, Diamant / Morita, Akimichi / Gooderham, Melinda / Foley, Peter / Girgis, Ihab G / Kundu, Sudeep / Banerjee, Subhashis. ·From K. Papp Clinical Research and Probity Medical Research, Waterloo (K.P.), the SKiN Centre for Dermatology and Probity Medical Research, Peterborough (M.G.), and Queen's University, Kingston (M.G.) - all in Ontario, Canada · Medical College of Wisconsin, Milwaukee (K.G.) · the University of Luebeck, Luebeck, Germany (D.T.) · Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan (A.M.) · the University of Melbourne, St. Vincent's Hospital Melbourne, Skin and Cancer Foundation, and Probity Medical Research, Melbourne, VIC, Australia (P.F.) · and Bristol-Myers Squibb, Princeton, NJ (I.G.G., S.K., S.B.). ·N Engl J Med · Pubmed #30205746.

ABSTRACT: BACKGROUND: Tyrosine kinase 2 (TYK2) signaling pathways, which mediate cytokine signaling, are implicated in the pathophysiology of psoriasis. Selective inhibitors of TYK2 may be effective in treating psoriasis. METHODS: We conducted a phase 2, double-blind trial of a TYK2 inhibitor, BMS-986165, in adults with moderate-to-severe psoriasis, excluding patients with a previous lack of response to agents targeting cytokine signaling through the same tyrosine kinase pathway. Patients were randomly assigned to receive the drug orally at a dose of 3 mg every other day, 3 mg daily, 3 mg twice daily, 6 mg twice daily, or 12 mg daily or to receive placebo. The primary end point was a 75% or greater reduction from baseline in the Psoriasis Area and Severity Index (PASI) score at week 12 (higher scores indicate greater severity of psoriasis). RESULTS: A total of 267 patients received at least one dose in an intervention group of the trial. At week 12, the percentage of patients with a 75% or greater reduction in the PASI score was 7% (3 of 45 patients) with placebo, 9% (4 of 44 patients) with 3 mg of BMS-986165 every other day (P=0.49 vs. placebo), 39% (17 of 44 patients) with 3 mg daily (P<0.001 vs. placebo), 69% (31 of 45 patients) with 3 mg twice daily (P<0.001 vs. placebo), 67% (30 of 45 patients) with 6 mg twice daily (P<0.001 vs. placebo), and 75% (33 of 44 patients) with 12 mg daily (P<0.001 vs. placebo). There were three serious adverse events in patients receiving the active drug, as well as one case of malignant melanoma 96 days after the start of treatment. CONCLUSIONS: Selective inhibition of TYK2 with the oral agent BMS-986165 at doses of 3 mg daily and higher resulted in greater clearing of psoriasis than did placebo over a period of 12 weeks. Larger and longer-duration trials of this drug are required to determine its safety and durability of effect in patients with psoriasis. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT02931838 .).

11 Clinical Trial Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials. 2018

Gordon, Kenneth B / Strober, Bruce / Lebwohl, Mark / Augustin, Matthias / Blauvelt, Andrew / Poulin, Yves / Papp, Kim A / Sofen, Howard / Puig, Lluís / Foley, Peter / Ohtsuki, Mamitaro / Flack, Mary / Geng, Ziqian / Gu, Yihua / Valdes, Joaquin M / Thompson, Elizabeth H Z / Bachelez, Hervé. ·Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: kegordon@mcw.edu. · University of Connecticut Health Center and Probity Medical Research, Farmington, CT, USA. · Icahn School of Medicine at Mount Sinai, New York, NY, USA. · University Medical Center Hamburg-Eppendorf, Hamburg, Germany. · Oregon Medical Research Center, Portland, OR, USA. · Centre Dermatologique du Québec Métropolitain, Québec, QC, Canada. · K Papp Clinical Research and Probity Medical Research, Waterloo, ON, Canada. · University of California, Los Angeles, CA, USA; School of Medicine, Los Angeles, CA, USA. · Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain. · University of Melbourne, Parkville, Skin & Cancer Foundation Inc, Carlton, Probity Medical Research, Carlton, and St Vincent's Hospital Melbourne, Fitzroy VIC, Australia. · Jichi Medical University, Shimotsuke, Japan. · Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT, USA. · AbbVie, North Chicago, IL, USA. · AbbVie, Redwood City, CA, USA. · Saint-Louis Hospital, AP-HP, Sorbonne Paris Cité Université Paris Diderot, INSERUM UMR 1163, Institut Imagine, Paris, France. Electronic address: herve.bachelez@aphp.fr. ·Lancet · Pubmed #30097359.

ABSTRACT: BACKGROUND: Risankizumab is a humanised IgG1 monoclonal antibody that binds to the p19 subunit of interleukin-23, inhibiting this key cytokine and its role in psoriatic inflammation. We aimed to assess the efficacy and safety of risankizumab compared with placebo or ustekinumab in patients with moderate-to-severe chronic plaque psoriasis. METHODS: UltIMMa-1 and UltIMMa-2 were replicate phase 3, randomised, double-blind, placebo-controlled and active comparator-controlled trials done at 139 sites in Australia, Austria, Belgium, Canada, Czech Republic, France, Germany, Japan, Mexico, Poland, Portugal, South Korea, Spain, and the USA. Eligible patients were 18 years or older, with moderate-to-severe chronic plaque psoriasis. In each study, patients were stratified by weight and previous exposure to tumour necrosis factor inhibitor and randomly assigned (3:1:1) by use of interactive response technology to receive 150 mg risankizumab, 45 mg or 90 mg ustekinumab (weight-based per label), or placebo. Following the 16-week double-blind treatment period (part A), patients initially assigned to placebo switched to 150 mg risankizumab at week 16; other patients continued their originally randomised treatment (part B, double-blind, weeks 16-52). Study drug was administered subcutaneously at weeks 0 and 4 during part A and at weeks 16, 28, and 40 during part B. Co-primary endpoints were proportions of patients achieving a 90% improvement in the Psoriasis Area Severity Index (PASI 90) and a static Physician's Global Assessment (sPGA) score of 0 or 1 at week 16 (non-responder imputation). All efficacy analyses were done in the intention-to-treat population. These trials are registered with ClinicalTrials.gov, numbers NCT02684370 (UltIMMa-1) and NCT02684357 (UltIMMa-2), and have been completed. FINDINGS: Between Feb 24, 2016, and Aug 31, 2016, 506 patients in UltIMMa-1 were randomly assigned to receive 150 mg risankizumab (n=304), 45 mg or 90 mg ustekinumab (n=100), or placebo (n=102). Between March 1, 2016, and Aug 30, 2016, 491 patients in UltIMMa-2 were randomly assigned to receive 150 mg risankizumab (n=294), 45 mg or 90 mg ustekinumab (n=99), or placebo (n=98). Co-primary endpoints were met for both studies. At week 16 of UltIMMa-1, PASI 90 was achieved by 229 (75·3%) patients receiving risankizumab versus five (4·9%) receiving placebo (placebo-adjusted difference 70·3% [95% CI 64·0-76·7]) and 42 (42·0%) receiving ustekinumab (ustekinumab-adjusted difference 33·5% [22·7-44·3]; p<0·0001 vs placebo and ustekinumab). At week 16 of UltIMMa-2, PASI 90 was achieved by 220 (74·8%) patients receiving risankizumab versus two (2·0%) receiving placebo (placebo-adjusted difference 72·5% [95% CI 66·8-78·2]) and 47 (47·5%) receiving ustekinumab (ustekinumab-adjusted difference 27·6% [16·7-38·5]; p<0·0001 vs placebo and ustekinumab). In UltIMMa-1, sPGA 0 or 1 at week 16 was achieved by 267 (87·8%) patients receiving risankizumab versus eight (7·8%) receiving placebo (placebo-adjusted difference 79·9% [95% CI 73·5-86·3]) and 63 (63·0%) receiving ustekinumab (ustekinumab-adjusted difference 25·1% [15·2-35·0]; p<0·0001 vs placebo and ustekinumab). In UltIMMa-2, 246 (83·7%) patients receiving risankizumab versus five (5·1%) receiving placebo (placebo-adjusted difference 78·5% [95% CI 72·4-84·5]) and 61 (61·6%) receiving ustekinumab achieved sPGA 0 or 1 at week 16 (ustekinumab-adjusted difference 22·3% [12·0-32·5]; p<0·0001 vs placebo and ustekinumab). The frequency of treatment-emergent adverse events in UltIMMa-1 and UltIMMa-2 was similar across risankizumab (part A: 151 [49·7%] of 304 and 134 [45·6%] of 294; part B: 182 [61·3%] of 297 and 162 [55·7%] of 291), placebo (part A: 52 [51·0%] of 102 and 45 [45·9%] of 98), ustekinumab (part A: 50 [50·0%] of 100 and 53 [53·5%] of 99; part B: 66 [66·7%] of 99 and 70 [74·5%] of 94), and placebo to risankizumab (part B: 65 [67·0%] of 97 and 61 [64·9%] of 94) treatment groups throughout the study duration. INTERPRETATION: Risankizumab showed superior efficacy to both placebo and ustekinumab in the treatment of moderate-to-severe plaque psoriasis. Treatment-emergent adverse event profiles were similar across treatment groups and there were no unexpected safety findings. FUNDING: AbbVie and Boehringer Ingelheim.

12 Clinical Trial Anxiety and depression in patients with moderate-to-severe psoriasis and comparison of change from baseline after treatment with guselkumab vs. adalimumab: results from the Phase 3 VOYAGE 2 study. 2018

Gordon, K B / Armstrong, A W / Han, C / Foley, P / Song, M / Wasfi, Y / You, Y / Shen, Y-K / Reich, K. ·Medical College of Wisconsin, Milwaukee, WI, USA. · University of Southern California, Los Angeles, CA, USA. · Janssen Research & Development, LLC, Spring House, PA, USA. · The University of Melbourne, St. Vincent's Hospital Melbourne, Skin & Cancer Foundation Inc., Carlton, VIC, Australia. · Dermatologikum Berlin, Berlin, Germany. ·J Eur Acad Dermatol Venereol · Pubmed #29706008.

ABSTRACT: BACKGROUND: Anxiety and depression are clinically significant comorbidities associated with psoriasis. Improvements in psoriasis are known to decrease anxiety and depression. Guselkumab, an anti-interleukin-23 monoclonal antibody, has demonstrated efficacy and safety for the treatment of moderate-to-severe psoriasis. OBJECTIVE: Assess improvements in anxiety and depression with guselkumab vs. placebo and adalimumab using the Hospital Anxiety and Depression Scale (HADS). METHODS: In VOYAGE 2, a Phase 3, randomized, double-blind, placebo- and adalimumab-controlled study, patients received placebo (through week 16 followed by crossover to guselkumab), guselkumab, or adalimumab through week 24. HADS consists of two subscales measuring anxiety (HADS-A) and depression (HADS-D), with scores ranging from 0 to 21 and higher scores indicating more severe symptoms. Scores ≥8 indicate instrument-defined anxiety or depression. Severity of psoriasis was assessed using the Psoriasis Area and Severity Index (PASI). RESULTS: Among 989 patients randomized (with baseline HADS measurements), mean HADS-A and HADS-D scores were 6.8 ± 4.2 and 5.3 ± 4.2, respectively; 38.6% of patients reported HADS-A ≥8 and 27.7% HADS-D ≥8 at baseline. At week 16, a significantly greater proportion of guselkumab patients with baseline HADS-A or HADS-D ≥8 reported HADS-A <8 (51.4% vs. 25.9%; P < 0.001) or HADS-D <8 (59.2% vs. 27.0%; P < 0.001) vs. placebo patients. At week 24, a greater proportion of guselkumab patients with baseline HADS-A or HADS-D ≥8 reported HADS-A <8 (58.4% vs. 42.9%; P = 0.028) or HADS-D <8 (59.8% vs. 46.4%; P = 0.079) vs. adalimumab patients. PASI improvements correlated with improvement in anxiety (r = 0.27; P < 0.0001) and depression (r = 0.25; P < 0.0001) scores in patients with baseline HADS-A or HADS-D ≥8. Greater improvements in HADS were also observed at week 16 in guselkumab-treated patients vs. placebo using a more stringent cut-off of HADS ≥11. CONCLUSION: Guselkumab treatment was associated with greater improvements in symptoms of anxiety and depression scores in patients with psoriasis compared with placebo and adalimumab.

13 Clinical Trial Efficacy and safety of ixekizumab over 4 years of open-label treatment in a phase 2 study in chronic plaque psoriasis. 2018

Zachariae, Claus / Gordon, Kenneth / Kimball, Alexandra B / Lebwohl, Mark / Blauvelt, Andrew / Leonardi, Craig / Braun, Daniel / McKean-Matthews, Missy / Burge, Russel / Cameron, Gregory. ·University Hospital of Copenhagen Gentofte, Copenhagen, Denmark. Electronic address: claus.zachariae@regionh.dk. · Medical College of Wisconsin, Milwaukee, Wisconsin. · Harvard Medical School, Boston, Massachusetts. · Mount Sinai Medical Center, New York, New York. · Oregon Medical Research Center, Portland, Oregon. · Department of Dermatology, Saint Louis University School of Medicine, St. Louis, Missouri. · Eli Lilly and Company, Indianapolis, Indiana. · Syneos Health, Ann Arbor, Michigan. ·J Am Acad Dermatol · Pubmed #29653208.

ABSTRACT: BACKGROUND: Ixekizumab has demonstrated improvement in patients with moderate-to-severe psoriasis by selectively targeting interleukin-17A, which is a proinflammatory cytokine that is important in the pathogenesis of psoriasis. OBJECTIVE: To report 4-year efficacy and safety results from the open-label extension (OLE) of this phase 2 trial. METHODS: Analysis was by last observation carried forward. Patients received ixekizumab, 120 mg, and then 80 mg subcutaneously once every 4 weeks. RESULTS: Of the patients who completed the randomized placebo-controlled trial, 93% entered the OLE. A 75% reduction in the Psoriasis Area Severity Index score was reported in 82% of patients at week 208 of the OLE. A static Physician's Global Assessment score of 0 or 1 was reported in 64% of patients, and a score of 0 was reported in 45% at week 208. Patients' Dermatology Life Quality Index and Itch Visual Analog Scale scores decreased when compared with baseline. Improvements were observed in other efficacy and health outcome measures. Serious adverse events were observed in 16.7% of patients, and 87% had 1 or more treatment-emergent adverse events. Three patients had serious infections. One patient reported 2 major cardiovascular events. LIMITATIONS: The study was unblinded and lacked a placebo or active comparator. CONCLUSIONS: Efficacy was shown to be maintained for up to 4 years of ixekizumab treatment.

14 Clinical Trial Adalimumab for nail psoriasis: Efficacy and safety from the first 26 weeks of a phase 3, randomized, placebo-controlled trial. 2018

Elewski, Boni E / Okun, Martin M / Papp, Kim / Baker, Christopher S / Crowley, Jeffrey J / Guillet, Gérard / Sundaram, Murali / Poulin, Yves / Gu, Yihua / Geng, Ziqian / Williams, David A / Rich, Phoebe A. ·University of Alabama at Birmingham School of Medicine, Birmingham, Alabama. Electronic address: beelewski@gmail.com. · Fort Healthcare, Fort Atkinson, Wisconsin. · K. Papp Clinical Research and Probity Medical Research, Waterloo, Ontario, Canada. · Skin and Cancer Foundation Inc and Probity Medical Research, Carlton, Victoria, Australia. · Bakersfield Dermatology, Bakersfield, California. · Hopital La Miletrie, Service de Dermatologie, CHU Poitiers, Poitiers, France. · Janssen Scientific Affairs, Horsham, Pennsylvania. · Centre de Recherche Dermatologique du Québec Métropolitain, Québec City, Québec, Canada; Laval University, Québec City, Québec, Canada. · AbbVie Inc, North Chicago, Illinois. · Oregon Health and Science University Hospital, Portland, Oregon. ·J Am Acad Dermatol · Pubmed #28993005.

ABSTRACT: BACKGROUND: Previous clinical trials have not evaluated improvement in nail psoriasis as a primary end point. OBJECTIVE: This phase 3 trial evaluated the safety and efficacy of adalimumab in patients with moderate-to-severe fingernail psoriasis and moderate-to-severe plaque psoriasis. METHODS: Patients were randomized 1:1 to 40 mg adalimumab every other week or placebo. The primary efficacy end point was at least 75% improvement in total-fingernail modified Nail Psoriasis Severity Index (NAPSI75) response rate at week 26. Ranked secondary end point scores evaluated at week 26 were total-fingernail NAPSI and modified NAPSI, nail pain, Nail Psoriasis Physical Functioning Severity, Brigham Scalp Nail Inverse Palmo-Plantar Psoriasis Index, and Physician's Global Assessment (fingernail psoriasis). RESULTS: Of the 217 randomized patients (108 received placebo and 109 received adalimumab), 188 (86.6%) completed 26 weeks of treatment (period A) or escaped early to the open-label period. The study met the primary end point (response rate of 3.4% with placebo vs 46.6% with adalimumab [P < .001]) and all ranked secondary end points. The serious adverse event rates (placebo vs adalimumab) in period A were 4.6% versus 7.3%; the serious infections rates were 1.9% versus 3.7%. LIMITATIONS: Patients with less than 5% BSA involvement were not eligible for enrollment. CONCLUSIONS: After 26 weeks of adalimumab treatment, significant improvements were seen in the primary and all ranked secondary end points and in signs and symptoms of moderate-to-severe nail psoriasis versus with placebo and no new safety risks were identified.

15 Clinical Trial Efficacy of guselkumab in subpopulations of patients with moderate-to-severe plaque psoriasis: a pooled analysis of the phase III VOYAGE 1 and VOYAGE 2 studies. 2018

Gordon, K B / Blauvelt, A / Foley, P / Song, M / Wasfi, Y / Randazzo, B / Shen, Y K / You, Y / Griffiths, C E M. ·Medical College of Wisconsin, Milwaukee, WI, U.S.A. · Oregon Medical Research Center, Portland, OR, U.S.A. · The University of Melbourne, St Vincent's Hospital, Melbourne, Australia. · Skin & Cancer Foundation Inc., Carlton, Victoria, Australia. · Janssen Research & Development, LLC, Spring House, PA, U.S.A. · The Dermatology Centre, Salford Royal Hospital, The University of Manchester, Manchester Academic Health Science Centre, Manchester, U.K. ·Br J Dermatol · Pubmed #28940259.

ABSTRACT: BACKGROUND: Significant advances have been made in the treatment of moderate-to-severe plaque psoriasis with biological therapies; however, these agents may not work equally in all populations. OBJECTIVES: To evaluate the efficacy of guselkumab in patient subgroups with moderate-to-severe psoriasis from the pooled guselkumab VOYAGE 1 and VOYAGE 2 phase III studies. METHODS: Using data from the pooled VOYAGE 1 and VOYAGE 2 psoriasis studies, analyses were performed to evaluate the consistency of efficacy [Investigator's Global Assessment (IGA) 0/1 (cleared or minimal psoriasis) and IGA 0 (cleared)] across subpopulations defined by demographics, baseline disease characteristics and previous psoriasis treatment. RESULTS: A total of 1829 patients were randomized. Baseline demographics, disease characteristics and previous psoriasis treatment were comparable across treatment groups in the pooled population. Guselkumab, an anti-interleukin (IL)-23 monoclonal antibody that binds to the p19 subunit of IL-23, provided substantial benefit across almost all subpopulations, with greater proportions of patients achieving IGA 0/1 vs. placebo at week 16, and vs. adalimumab (an antitumour necrosis factor monoclonal antibody) at week 24. Patients treated with guselkumab achieved greater efficacy (IGA 0/1 and IGA 0) compared with adalimumab at week 24 across all weight quartiles, most notably among patients weighing ≥ 100 kg. CONCLUSIONS: This analysis demonstrates a high degree of efficacy with guselkumab treatment compared with placebo at week 16 and with adalimumab at week 24 among broad subpopulations of patients with varying baseline demographics, disease characteristics and previous psoriasis treatments.

16 Clinical Trial Poor early response to methotrexate portends inadequate long-term outcomes in patients with moderate-to-severe psoriasis: Evidence from 2 phase 3 clinical trials. 2017

Gordon, Kenneth B / Betts, Keith A / Sundaram, Murali / Signorovitch, James E / Li, Junlong / Xie, Meng / Wu, Eric Q / Okun, Martin M. ·Medical College of Wisconsin, Milwaukee, Wisconsin. · Analysis Group Inc, Boston, Massachusetts. Electronic address: keith.betts@analysisgroup.com. · AbbVie Inc, North Chicago, Illinois. · Analysis Group Inc, Boston, Massachusetts. · AbbVie Inc, North Chicago, Illinois; Fort HealthCare, Fort Atkinson, Wisconsin. ·J Am Acad Dermatol · Pubmed #28993007.

ABSTRACT: BACKGROUND: Most methotrexate-treated psoriasis patients do not achieve a long-term PASI75 (75% reduction from baseline Psoriasis Area and Severity Index score) response. Indications of nonresponse can be apparent after only 4 weeks of treatment. OBJECTIVE: To develop a prediction rule to identify patients unlikely to respond adequately to methotrexate. METHODS: Patient-level data from CHAMPION (NCT00235820, N = 110) was used to construct a prediction model for week 16 PASI75 by using patient baseline characteristics and week 4 PASI25. A prediction rule was determined on the basis of the sensitivity and specificity and validated in terms of week 16 PASI75 response in an independent validation sample from trial M10-255 (NCT00679731, N = 163). RESULTS: PASI25 achievement at week 4 (odds ratio = 8.917) was highly predictive of response with methotrexate at week 16. Patients with a predicted response probability <30% were recommended to discontinue methotrexate. The rates of week 16 PASI75 response were 65.8% and 21.1% (P < .001) for patients recommended to continue and discontinue methotrexate, respectively. LIMITATIONS: The CHAMPION trial excluded patients previously treated with biologics, and the M10-255 trial had no restrictions. CONCLUSION: A prediction rule was developed and validated to identify patients unlikely to respond adequately to methotrexate. The rule indicates that 4 weeks of methotrexate might be sufficient to predict long-term response with limited safety risk.

17 Clinical Trial Impact of immunogenicity on pharmacokinetics, efficacy and safety of adalimumab in adult patients with moderate to severe chronic plaque psoriasis. 2017

Mostafa, N M / Nader, A M / Noertersheuser, P / Okun, M / Awni, W M. ·AbbVie Inc., North Chicago, IL, USA. · Fort Healthcare, Fort Atkinson, WI, USA. ·J Eur Acad Dermatol Venereol · Pubmed #27545848.

ABSTRACT: BACKGROUND: Adalimumab is a tumour necrosis factor-alpha antibody approved for treatment of moderate to severe chronic plaque psoriasis. OBJECTIVE: To characterise population pharmacokinetics of adalimumab 40 mg every other week dosing regimen and impact of immunogenicity on pharmacokinetics, efficacy and safety in psoriasis patients. METHODS: Patients were enrolled in a Phase 3 study comprising a 16-week double-blind, placebo-controlled period, a 17-week open-label period for Week 16 Psoriasis Area and Severity Index (PASI) 75 responders, and a 19-week double-blind, placebo-controlled period for Week 33 PASI 75 responders. Serum adalimumab and anti-adalimumab antibody (AAA) concentrations were measured and a population pharmacokinetic model devleoped to identify patient/disease factors affecting adalimumab pharmacokinetics. Impact of immunogenicity on treatment efficacy and safety was also assessed. RESULTS: Week 33 mean adalimumab concentration was 5.2 μg/mL. Week 16 responders had higher adalimumab concentrations than non-responders (6.3 vs. 2.2 μg/mL). Bodyweight and study were significant covariates in population pharmacokinetic model with weight accounting for 19% and 29% of variability in adalimumab clearance and volume of distribution, respectively. A total of 8.8% of adalimumab-treated patients tested AAA positive and had twofold higher adalimumab clearance. PASI 75 response rate was comparable between AAA+ and AAA- patients at Weeks 33 and 52 (Week 33: 36% vs. 22.5%, Week 52: 21.1% vs. 17.8%) and adverse events incidence was similar between the two groups. CONCLUSIONS: Patient weight and study significantly affect adalimumab clearance and volume of distribution in psoriasis patients. Development of AAAs result in lower adalimumab exposure and efficacy with no effect on adverse events incidence.

18 Clinical Trial Efficacy and safety of adalimumab in Chinese patients with moderate-to-severe plaque psoriasis: results from a phase 3, randomized, placebo-controlled, double-blind study. 2017

Cai, L / Gu, J / Zheng, J / Zheng, M / Wang, G / Xi, L-Y / Hao, F / Liu, X-M / Sun, Q-N / Wang, Y / Lai, W / Fang, H / Tu, Y-T / Sun, Q / Chen, J / Gao, X-H / Gu, Y / Teixeira, H D / Zhang, J-Z / Okun, M M. ·Peking University People's Hospital, Beijing, China. · Shanghai Changhai Hospital, Shanghai, China. · Ruijin Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, China. · Second Affiliated Hospital Zhejiang University College of Medicine, Hangzhou, China. · The first Affiliated Hospital of Fourth Military Medical University, PLA (Xijing Hospital), Xi'an, China. · Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. · The First Affiliated Hospital of Third Military Medical University, PLA (Southwest Hospital), Chongqing, China. · First Affiliated Hospital of Dalian Medical University, Dalian, China. · Peking Union Medical College Hospital, Beijing, China. · Peking University First Hospital, Beijing, China. · The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. · The First Affiliated Hospital of College of Medicine, Zhejiang University, Hangzhou, China. · Union Hospital Tongji Medical College Huazhong University of Science and Technology, Wuhan, China. · Qilu Hospital of Shandong University, Jinan, China. · Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, China. · The First Hospital of China Medical University, Shenyang, China. · AbbVie Inc., North Chicago, IL, USA. · Fort HealthCare, Fort Atkinson, WI, USA. ·J Eur Acad Dermatol Venereol · Pubmed #27504914.

ABSTRACT: BACKGROUND: This phase 3 trial is the first to evaluate the efficacy and safety of treatment with the systemic TNF-α inhibitor, adalimumab, for Chinese patients with moderate-to-severe plaque psoriasis. METHODS: In the 12-week, double-blind, placebo-controlled Period A, patients were randomized 4 : 1 to receive adalimumab 40 mg every-other-week (following a single 80 mg dose), or placebo every-other-week. In the subsequent 12-week, open-label, Period B, all patients received adalimumab 40 mg every-other-week starting at week 13, following a single, blinded dose at week 12 of adalimumab 80 mg or matching placebo (for patients receiving placebo or adalimumab in Period A respectively). In Period A, efficacy was analysed for all randomized patients and safety for all patients receiving ≥1 dose of the study drug. RESULTS: For the 425 patients in this study (87 placebo; 338 adalimumab), a higher percentage randomized to adalimumab achieved the primary endpoint of ≥75% improvement from baseline in PASI score (PASI 75) at week 12: placebo 11.5% (10/87); adalimumab 77.8% (263/338; P < 0.001). Physician's Global Assessment of clear to minimal was achieved at week 12 by 14.9% placebo (13/87) and 80.5% adalimumab (272/338; P < 0.001). For patients who received adalimumab at any time during the study (All-adalimumab Population), treatment-emergent adverse events (AEs) were reported by 63.4%; the most common was upper respiratory infection (16.1%). Serious AEs were reported by 3.5% of the All-adalimumab Population, and serious infectious AEs by 1.2%, which include lung infection, pneumonia and tuberculosis [2 (0.5%) patients each]. There was one death (chronic heart failure). CONCLUSION: In these Chinese patients with moderate-to-severe psoriasis, a significantly greater percentage treated with adalimumab compared with placebo achieved efficacy endpoints at week 12 and efficacy was sustained to week 24. Safety results were consistent with the known adalimumab safety profile; no new safety signals were identified in the 24 weeks of treatment.

19 Article Genetic signature to provide robust risk assessment of psoriatic arthritis development in psoriasis patients. 2018

Patrick, Matthew T / Stuart, Philip E / Raja, Kalpana / Gudjonsson, Johann E / Tejasvi, Trilokraj / Yang, Jingjing / Chandran, Vinod / Das, Sayantan / Callis-Duffin, Kristina / Ellinghaus, Eva / Enerbäck, Charlotta / Esko, Tõnu / Franke, Andre / Kang, Hyun M / Krueger, Gerald G / Lim, Henry W / Rahman, Proton / Rosen, Cheryl F / Weidinger, Stephan / Weichenthal, Michael / Wen, Xiaoquan / Voorhees, John J / Abecasis, Gonçalo R / Gladman, Dafna D / Nair, Rajan P / Elder, James T / Tsoi, Lam C. ·Department of Dermatology, University of Michigan Medical School, Ann Arbor, 48109, MI, USA. · Morgridge Institute for Research, Madison, 53715, WI, USA. · Ann Arbor Veterans Affairs Hospital, Ann Arbor, 48105, MI, USA. · Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, 48109, MI, USA. · Department of Human Genetics, Emory University School of Medicine, Atlanta, 30322, GA, USA. · Department of Medicine, Division of Rheumatology, University of Toronto, Toronto, Ontario, M5G 2C4, Canada. · Centre for Prognosis Studies in the Rheumatic Diseases, Krembil Research Institute, University of Toronto, Toronto, Ontario, M5T 2S8, Canada. · Institute of Medical Science, University of Toronto, Toronto, Ontario, M5S 1A8, Canada. · Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada. · Department of Dermatology, University of Utah, Salt Lake City, Utah, 84132, USA. · Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, 24105, Germany. · Department of Dermatology, Linköping University, Linköping, SE-581 83, Sweden. · Estonian Genome Center, University of Tartu, Tartu, 51010, Estonia. · Broad Institute of MIT and Harvard, Cambridge, Massachusetts, 02142, USA. · Department of Dermatology, Henry Ford Hospital, Detroit, 48202, MI, USA. · Memorial University, St. John's, Newfoundland and Labrador, A1B 3X9, Canada. · Division of Dermatology, Toronto Western Hospital, University of Toronto, Toronto, M5G 2C4, Ontario, Canada. · Department of Dermatology, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, 24105, Germany. · Department of Dermatology, University of Michigan Medical School, Ann Arbor, 48109, MI, USA. alextsoi@med.umich.edu. · Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, 48109, MI, USA. alextsoi@med.umich.edu. · Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, 4810, MI, USA. alextsoi@med.umich.edu. ·Nat Commun · Pubmed #30301895.

ABSTRACT: Psoriatic arthritis (PsA) is a complex chronic musculoskeletal condition that occurs in ~30% of psoriasis patients. Currently, no systematic strategy is available that utilizes the differences in genetic architecture between PsA and cutaneous-only psoriasis (PsC) to assess PsA risk before symptoms appear. Here, we introduce a computational pipeline for predicting PsA among psoriasis patients using data from six cohorts with >7000 genotyped PsA and PsC patients. We identify 9 new loci for psoriasis or its subtypes and achieve 0.82 area under the receiver operator curve in distinguishing PsA vs. PsC when using 200 genetic markers. Among the top 5% of our PsA prediction we achieve >90% precision with 100% specificity and 16% recall for predicting PsA among psoriatic patients, using conditional inference forest or shrinkage discriminant analysis. Combining statistical and machine-learning techniques, we show that the underlying genetic differences between psoriasis subtypes can be used for individualized subtype risk assessment.

20 Article Systematic review of the real-world evidence of adalimumab safety in psoriasis registries. 2018

Strober, B / Crowley, J / Langley, R G / Gordon, K / Menter, A / Leonardi, C / Arikan, D / Valdecantos, W C. ·Department of Dermatology, University of Connecticut, Farmington, CT, USA. · Probity Medical Research, Waterloo, ON, Canada. · Bakersfield Dermatology, Bakersfield, CA, USA. · Dalhousie University, Halifax, NS, Canada. · Medical College of Wisconsin, Milwaukee, WI, USA. · Baylor University Medical Center, Dallas, TX, USA. · Saint Louis University, St. Louis, MO, USA. · AbbVie Inc., North Chicago, IL, USA. ·J Eur Acad Dermatol Venereol · Pubmed #30067882.

ABSTRACT: Long-term safety of adalimumab in psoriasis clinical studies has been established. The objective of this research was to review real-world evidence of adalimumab safety from registries of adult patients with psoriasis treated in clinical practice. Databases (BIOSIS Previews, Current Contents Search, Derwent Drug File, EMBASE, EMBASE Alert, EMCare, MEDLINE, SciSearch) were searched for psoriasis registries with adalimumab safety data. Eligible papers were English language manuscripts (conference abstracts excluded) from psoriasis registries presenting safety data for adult patients with psoriasis receiving adalimumab. The incidence and rate (events/100 patient-years [PY]) of adverse events (AEs), serious AEs (SAEs) and AEs of special interest are reported. Abstracts of 425 publications were screened, and 401 publications excluded (208 conference abstracts; 193 papers). Remaining manuscripts were fully screened; 14 were excluded (no adalimumab data, n = 10; no safety data, n = 2; no on-treatment data, n = 1; not English, n = 1), and 10 selected. Overall rates of AEs (4273 [22.2/100PY]) and SAEs (827 [4.3/100PY]) were reported in the ESPRIT registry (N = 6059). Rates of infections (7.7-14.7/100PY) and serious infections (<0.6-2.0/100PY) were reported in four studies. Cardiovascular-related events were reported in three studies: ≤0.1/100PY per major cardiac event in ESPRIT, <0.5/100PY major cardiac events in PsoBest and serious cardiovascular events in two patients (<1%) in DERMBIO. Malignancies were reported in three studies (any malignancy, 0.9/100PY; malignancies excluding non-melanoma skin cancer [NMSC], <0.6/100PY; NMSC, 0.6-<0.5/100PY). These findings suggest that real-world safety of adalimumab is consistent across different psoriasis registries, which supports the existing long-term safety profile of adalimumab from clinical studies.

21 Article Chitosan-based nanoformulated (-)-epigallocatechin-3-gallate (EGCG) modulates human keratinocyte-induced responses and alleviates imiquimod-induced murine psoriasiform dermatitis. 2018

Chamcheu, Jean Christopher / Siddiqui, Imtiaz A / Adhami, Vaqar M / Esnault, Stephane / Bharali, Dhruba J / Babatunde, Abiola S / Adame, Stephanie / Massey, Randall J / Wood, Gary S / Longley, B Jack / Mousa, Shaker A / Mukhtar, Hasan. ·Department of Dermatology, School of Medicine and Public Health, The University of Wisconsin-Madison, Madison, WI, USA, chamcheu@ulm.edu. · School of Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA, USA, chamcheu@ulm.edu. · Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, The University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA. · The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY, USA. · Department of Hematology, University of Ilorin, Ilorin, Nigeria. · Electron Microscope Facility, Medical School Research Support Programs, School of Medicine and Public Health, The University of Wisconsin-Madison, Madison, WI, USA. ·Int J Nanomedicine · Pubmed #30057446.

ABSTRACT: Background: Psoriasis is a chronic and currently incurable inflammatory skin disease characterized by hyperproliferation, aberrant differentiation, and inflammation, leading to disrupted skin barrier function. The use of natural agents that can abrogate these effects could be useful for the treatment of psoriasis. Earlier studies have shown that treatment of keratinocytes and mouse skin with the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) mitigated inflammation and increased the expression of caspase-14 while promoting epidermal differentiation and cornification. However, bioavailability issues have restricted the development of EGCG for the treatment of psoriasis. Materials and methods: To overcome these limitations, we employed a chitosan-based polymeric nanoparticle formulation of EGCG (CHI-EGCG-NPs, hereafter termed nanoEGCG) suitable for topical delivery for treating psoriasis. We investigated and compared the efficacy of nanoEGCG versus native or free EGCG in vitro and in an in vivo imiquimod (IMQ)-induced murine psoriasis-like dermatitis model. The in vivo relevance and efficacy of nanoEGCG formulation (48 µg/mouse) were assessed in an IMQ-induced mouse psoriasis-like skin lesion model compared to free EGCG (1 mg/mouse). Results: Like free EGCG, nanoEGCG treatment induced differentiation, and decreased proliferation and inflammatory responses in cultured keratinocytes, but with a 4-fold dose advantage. Topically applied nanoEGCG elicited a significant ( Conclusion: Based on these observations, our nanoEGCG formulation represents a promising drug-delivery strategy for treating psoriasis and possibly other inflammatory skin diseases.

22 Article CARD14-associated papulosquamous eruption: A spectrum including features of psoriasis and pityriasis rubra pilaris. 2018

Craiglow, Brittany G / Boyden, Lynn M / Hu, Ronghua / Virtanen, Marie / Su, John / Rodriguez, Gabriela / McCarthy, Catherine / Luna, Paula / Larralde, Margarita / Humphrey, Stephen / Holland, Kristen E / Hogeling, Marcia / Hidalgo-Matlock, Benjamin / Ferrari, Bruno / Fernandez-Faith, Esteban / Drolet, Beth / Cordoro, Kelly M / Bowcock, Anne M / Antaya, Richard J / Ashack, Kurt / Ashack, Richard J / Lifton, Richard P / Milstone, Leonard M / Paller, Amy S / Choate, Keith A. ·Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut. · Department of Genetics, Yale University School of Medicine, New Haven, Connecticut. · Department of Dermatology, Uppsala University Hospital, Uppsala, Sweden. · Department of Dermatology, Monash University, Eastern Health, Melbourne, Australia; Department of Pediatrics, Murdoch Children's Research Institute, University of Melbourne, Melbourne, Australia. · Department of Dermatology, University of Costa Rica, San Jose, Costa Rica. · Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri. · Department of Pediatric Dermatology, Ramos Mejía Hospital, Buenos Aires, Argentina. · Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin. · Division of Dermatology, David Geffen School of Medicine at University of California, Los Angeles, California. · Department of Pediatrics and Dermatology, The Ohio State University Medical Center, Columbus, Ohio; Department of Pediatrics and Dermatology, Nationwide Children's Hospital, Columbus, Ohio. · Department of Dermatology, University of California, San Francisco, California; Department of Pediatrics, University of California, San Francisco, California. · Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Genetics and Genome Sciences, Icahn School of Medicine at Mount Sinai, New York, New York. · Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut; Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut. · Department of Dermatology, University of Illinois at Chicago College of Medicine, Chicago, Illinois. · Dermatology Associates of West Michigan, Grand Rapids, Michigan. · Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois. · Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut; Department of Genetics, Yale University School of Medicine, New Haven, Connecticut; Department of Pathology, Yale University School of Medicine, New Haven, Connecticut. Electronic address: keith.choate@yale.edu. ·J Am Acad Dermatol · Pubmed #29477734.

ABSTRACT: BACKGROUND: Heterozygous mutations in caspase recruitment domain family member 14 gene (CARD14) have been shown to be associated with psoriasis and familial pityriasis rubra pilaris (PRP). Many subjects with CARD14 mutations display features of both disorders, which can result in diagnostic uncertainty. In addition, these eruptions are often recalcitrant to conventional psoriasis therapies such as methotrexate, oral retinoids, and tumor necrosis factor-α inhibitors. OBJECTIVE: We sought to describe the clinical characteristics, family history, and response to therapy in subjects with papulosquamous eruptions due to mutations in CARD14. METHODS: Subjects were referred for genetic testing as part of a registry of subjects with inherited disorders of keratinization. DNA was isolated from blood or saliva, and multiplex targeted sequencing or whole exome sequencing was performed. Clinical histories of subjects with CARD14 mutations were reviewed. RESULTS: We identified 15 kindreds with CARD14-associated papulosquamous eruption (CAPE). Characteristic features of CAPE include early age of onset; prominent involvement of the cheeks, chin, and ears; family history of psoriasis or PRP; minimal response to conventional topical and systemic psoriasis therapies; and improvement with ustekinumab. LIMITATIONS: Relatively small sample size. CONCLUSIONS: Many subjects with CARD14 mutations display characteristics of both psoriasis and PRP. We propose the term CARD14-associated papulosquamous eruption to describe this spectrum of disease. Subjects with clinical features suggestive of CAPE should undergo CARD14 sequencing and may benefit from treatment with ustekinumab.

23 Article Bioactive Dietary VDR Ligands Regulate Genes Encoding Biomarkers of Skin Repair That Are Associated with Risk for Psoriasis. 2018

Karrys, Amitis / Rady, Islam / Chamcheu, Roxane-Cherille N / Sabir, Marya S / Mallick, Sanchita / Chamcheu, Jean Christopher / Jurutka, Peter W / Haussler, Mark R / Whitfield, G Kerr. ·School of Life Sciences, Arizona State University, Tempe, AZ 85281, USA. tkarrys12@gmail.com. · Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, Phoenix, AZ 85004, USA. tkarrys12@gmail.com. · Department of Dermatology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706, USA. irady@dermatology.wisc.edu. · Department of Zoology, Faculty of Science, Al-Azhar University, P.O. Box 11884 Nazr City, Cairo, Egypt. irady@dermatology.wisc.edu. · Department of Dermatology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706, USA. roxanechamcheu@gmail.com. · School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ 85306, USA. msabir@asu.edu. · School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ 85306, USA. smallic5@asu.edu. · Department of Dermatology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706, USA. chamcheu@ulm.edu. · Department of Basic Pharmaceutical Sciences, School of Pharmacy, College of Health & Pharmaceutical Sciences, University of Louisiana at Monroe, 1800 Bienville Drive, Bienville 362, Monroe, LA 71201, USA. chamcheu@ulm.edu. · Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, Phoenix, AZ 85004, USA. peter.jurutka@asu.edu. · School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ 85306, USA. peter.jurutka@asu.edu. · Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, Phoenix, AZ 85004, USA. haussler@email.arizona.edu. · Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, Phoenix, AZ 85004, USA. gkw@email.arizona.edu. ·Nutrients · Pubmed #29401702.

ABSTRACT: Treatment with 1,25-dihydroxyvitamin D₃ (1,25D) improves psoriasis symptoms, possibly by inducing the expression of late cornified envelope (

24 Article Depressive symptoms, depression, and the effect of biologic therapy among patients in Psoriasis Longitudinal Assessment and Registry (PSOLAR). 2018

Strober, Bruce / Gooderham, Melinda / de Jong, Elke M G J / Kimball, Alexa B / Langley, Richard G / Lakdawala, Nikita / Goyal, Kavitha / Lawson, Fabio / Langholff, Wayne / Hopkins, Lori / Fakharzadeh, Steve / Srivastava, Bhaskar / Menter, Alan. ·University of Connecticut Health Center, Farmington, Connecticut; Probity Medical Research, Waterloo, Ontario, Canada. Electronic address: strober@uchc.edu. · Queen's University, Kingston, Ontario, Canada; SKiN Centre for Dermatology, Peterborough, Ontario, Canada. · Radboud University Medical Center and Radboud University, Nijmegen, The Netherlands. · Beth Israel Deaconess Hospital and Harvard Medical School, Boston, Massachusetts. · Dalhousie University, Halifax, Nova Scotia, Canada. · Medical College of Wisconsin, Milwaukee, Wisconsin. · Janssen Scientific Affairs, LLC, Horsham, Pennsylvania. · Janssen Research & Development, LLC, Spring House, Pennsylvania. · Baylor University Medical Center at Dallas, Dallas, Texas. ·J Am Acad Dermatol · Pubmed #29102053.

ABSTRACT: BACKGROUND: Patients with psoriasis are at an increased risk for depression. However, the impact of treatment on this risk is unclear. OBJECTIVE: Evaluate the incidence and impact of treatment on depression among patients with moderate-to-severe psoriasis. METHODS: We defined a study population within the Psoriasis Longitudinal Assessment and Registry and measured the incidence of depressive symptoms (Hospital Anxiety and Depression Scale-Depression score ≥8) and adverse events (AEs) of depression within cohorts receiving biologics, conventional systemic therapies, or phototherapy. Patients were evaluated at approximately 6-month intervals. Multivariate modeling determined the impact of treatment on risk. RESULTS: The incidence rates of depressive symptoms were 3.01 per 100 patient-years (PYs) (95% confidence interval [CI], 2.73-3.32), 5.85 per 100 PYs (95% CI, 4.29-7.97), and 5.70 per 100 PYs (95% CI, 4.58-7.10) for biologics, phototherapy, and conventional therapy, respectively. Compared with conventional therapy, biologics reduced the risk for depressive symptoms (hazard ratio, 0.76; 95% CI, 0.59-0.98), whereas phototherapy did not (hazard ratio, 1.05; 95% CI, 0.71-1.54). The incidence rates for AEs of depression were 0.21 per 100 PYs (95% CI, 0.15-0.31) for biologics, 0.55 per 100 PYs (95% CI, 0.21-1.47) for phototherapy, and 0.14 per 100 PYs (95% CI, 0.03-0.55) for conventional therapy; the fact that there were too few events (37 AEs) precluded modeling. LIMITATIONS: Incomplete capture of depression and confounders in the patients on registry. CONCLUSION: Compared with conventional therapy, biologics appear to be associated with a lower incidence of depressive symptoms among patients with psoriasis.

25 Article Protein engineering of the chemokine CCL20 prevents psoriasiform dermatitis in an IL-23-dependent murine model. 2017

Getschman, A E / Imai, Y / Larsen, O / Peterson, F C / Wu, X / Rosenkilde, M M / Hwang, S T / Volkman, B F. ·Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226. · Department of Dermatology, Medical College of Wisconsin, Milwaukee, WI 53226. · Department of Dermatology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan. · Laboratory for Molecular Pharmacology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, The Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark. · Department of Dermatology, University of California Davis School of Medicine, Sacramento, CA 95816. · Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226; bvolkman@mcw.edu. ·Proc Natl Acad Sci U S A · Pubmed #29109267.

ABSTRACT: Psoriasis is a chronic inflammatory skin disease characterized by the infiltration of T cell and other immune cells to the skin in response to injury or autoantigens. Conventional, as well as unconventional, γδ T cells are recruited to the dermis and epidermis by CCL20 and other chemokines. Together with its receptor CCR6, CCL20 plays a critical role in the development of psoriasiform dermatitis in mouse models. We screened a panel of CCL20 variants designed to form dimers stabilized by intermolecular disulfide bonds. A single-atom substitution yielded a CCL20 variant (CCL20 S64C) that acted as a partial agonist for the chemokine receptor CCR6. CCL20 S64C bound CCR6 and induced intracellular calcium release, consistent with G-protein activation, but exhibited minimal chemotactic activity. Instead, CCL20 S64C inhibited CCR6-mediated T cell migration with nominal impact on other chemokine receptor signaling. When given in an IL-23-dependent mouse model for psoriasis, CCL20 S64C prevented psoriatic inflammation and the up-regulation of IL-17A and IL-22. Our results validate CCR6 as a tractable therapeutic target for psoriasis and demonstrate the value of CCL20 S64C as a lead compound.

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