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Il-23 and psoriasis

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https://www.readbyqxmd.com/read/29043884/guselkumab-for-psoriasis-a-critical-appraisal-of-phase-iii-studies
#1
Zenas Zn Yiu, Richard B Warren
Biologic therapies have raised the frontiers of accepted treatment efficacy for severe psoriasis. Guselkumab is an IgG1 monoclonal antibody that binds to the p19 subunit and inhibits IL-23. In three Phase III randomized, active comparator and placebo controlled trials, guselkumab demonstrated superior efficacy and a comparable safety profile when assessed against adalimumab and ustekinumab. Critical appraisal highlighted uncertainties over risk of bias from missing details in the trial publications that would be overcome with the provision of accompanying trial protocols, as well as the need for a head-to-head trial against an IL-17 inhibitor...
October 18, 2017: Immunotherapy
https://www.readbyqxmd.com/read/29022425/biologics-in-pediatric-psoriasis-efficacy-and-safety
#2
Sunil Dogra, Rahul Mahajan
Introduction Childhood psoriasis is a special situation that is a management challenge for the treating dermatologist. As is the situation with traditional systemic agents, which are commonly used in managing severe psoriasis in children, the biologics are being increasingly used in the recalcitrant disease despite limited data on long term safety. Areas covered - We performed an extensive literature search to collect evidence-based data on the use of biologics in pediatric psoriasis. The relevant literature published from 2000 to September 2017 was obtained from PubMed, using the MeSH words 'biologics', 'biologic response modifiers' or 'treatment of pediatric/childhood psoriasis'...
October 12, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28994166/newer-treatments-of-psoriasis-regarding-il-23-inhibitors-phosphodiesterase-4-inhibitors-and-janus-kinase-inhibitors
#3
REVIEW
Dominika Wcisło-Dziadecka, Martyna Zbiciak-Nylec, Ligia Brzezińska-Wcisło, Katarzyna Bebenek, Agata Kaźmierczak
The rapid progress of genetic engineering furthermore opens up new prospects in the therapy of this difficult-to-treat disease. IL-23 inhibitors, phosphodiesterase 4 (PDE4) inhibitors, and Janus kinase (JAK) inhibitors are currently encouraging further research. Two drugs which are IL-23 inhibitors are now in phase III of clinical trials. The aim of the action of both drugs is selective IL-23 inhibition by targeting the p19 subunit. Guselkumab is a fully human monoclonal antibody. Tildrakizumab is a humanized monoclonal antibody, which also belongs to IgG class and is targeted to subunit p19 of interleukin 23 (IL-23)...
October 10, 2017: Dermatologic Therapy
https://www.readbyqxmd.com/read/28980716/metabolic-parameters-in-psoriatic-patients-treated-with-interleukin-12-23-blockade-ustekinumab
#4
Chau Yee Ng, I-Shiang Tzeng, Su-Hsun Liu, Ya-Ching Chang, Yu-Huei Huang
The associations between psoriasis, metabolic syndrome and cardiovascular events are increasingly recognized. Studies have shown decreased cardiovascular events with the treatment of methotrexate and anti-tumor necrosis factor, however, effects of interleukin (IL)-12/23 blockade remain debatable. Our study investigated the effect of IL-12/23 blockade on the metabolic parameters in patients with psoriasis. We performed a retrospective cohort study to assess 93 consecutive patients with moderate to severe plaque type psoriasis who received IL-12/23 blockade (ustekinumab) for 24 weeks between January 2012 and May 2016...
October 5, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/28972090/il-17-secreting-%C3%AE-%C3%AE-t-cells-are-completely-dependent-upon-ccr6-for-homing-to-inflamed-skin
#5
James J Campbell, Karen Ebsworth, Linda S Ertl, Jeffrey P McMahon, Dale Newland, Yu Wang, Shirley Liu, Zhenhua Miao, Ton Dang, Penglie Zhang, Israel F Charo, Rajinder Singh, Thomas J Schall
mAbs that neutralize IL-17 or its receptor have proven efficacious in treating moderate-to-severe psoriasis, confirming IL-17 as an important driver of this disease. In mice, a rare population of T cells, γδT17 cells, appears to be a dominant source of IL-17 in experimental psoriasis. These cells traffic between lymph nodes and the skin, and are identified by their coexpression of the TCR variable regions γ4 and δ4. These cells are homologous to the Vγ9Vδ2 T cell population identified in human psoriatic plaques...
September 29, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28967976/highlighting-interleukin-36-signalling-in-plaque-psoriasis-and-pustular-psoriasis
#6
Kazuhisa Furue, Kazuhiko Yamamura, Gaku Tsuji, Chikage Mitoma, Hiroshi Uchi, Takeshi Nakahara, Makiko Kido-Nakahara, Takafumi Kadono, Masutaka Furue
Plaque psoriasis and pustular psoriasis are overlapping, but distinct, disorders. The therapeutic response to biologics supports the pivotal role of the tumour necrosis alpha (TNF-α)/ interleukin (IL)-23/IL-17/IL-22 axis in the pathogenesis of these disorders. Recently, functional activation of the IL-36 receptor (IL-36R) was discovered to be another driving force in the pathogenesis of psoriasis. This was first highlighted by the discovery that a loss-of-function mutation of the IL-36R antagonist (IL-36Ra) causes pustular psoriasis...
October 2, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/28960267/anti-il-23-and-anti-il-17-biologic-agents-for-the-treatment-of-immune-mediated-inflammatory-conditions
#7
Jillian Frieder, Dario Kivelevitch, Isabel Haugh, Ian Watson, Alan Menter
Advancements in the immunopathogenesis of psoriasis have identified interleukin (IL)-23 and IL-17 as fundamental contributors in the immune pathways of the disease. Leveraging these promising therapeutic targets has led to the emergence of a number of anti-IL-23 and -17 biologic agents with the potential to treat multiple conditions with common underlying pathology. The unprecedented clinical efficacy of these agents in the treatment of psoriasis has paved way for their evaluation in diseases such as psoriatic arthritis, Crohn's disease, rheumatoid arthritis, in addition to other immune-mediated conditions...
September 28, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28956015/human-umbilical-cord-blood-derived-mesenchymal-stem-cells-ameliorate-psoriasis-like-skin-inflammation-in-mice
#8
Yun Sang Lee, Shyam Kishor Sah, Ji Hyun Lee, Kwang-Won Seo, Kyung-Sun Kang, Tae-Yoon Kim
Mesenchymal stem cells (MSCs) inhibit the proliferation or activation of lymphocytes, and their inhibitory effects do not require human leukocyte antigen (HLA)-matching because MSCs express low levels of HLA molecules. Therefore, MSCs may be able to regulate immune responses. In this study, we determined whether MSCs could inhibit psoriasis-like skin inflammation in mice. After induction of psoriasis-like skin inflammation using intradermal injection of IL-23 or topical application of imiquimod with or without treatment with MSC, mouse skins were collected, and H&E staining and real-time PCR were performed...
March 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28951241/protection-from-psoriasis-related-thrombosis-following-inhibition-of-il-23-or-il-17a
#9
Yumeng Li, Jackelyn B Golden, Maya I Camhi, Xiufen Zhang, Yi Fritz, Doina Diaconu, Tammy L Ivanco, Daniel I Simon, Kristine Kikly, Thomas S McCormick, Yunmei Wang, Nicole L Ward
Psoriasis patients experience chronic systemic skin inflammation and develop cardiovascular comorbidities that shorten their lifespan. Whether cardiovascular disease is improved by treatment with current biologics that target disease-specific pathways is unclear. KC-Tie2 mice develop psoriasiform skin inflammation with increases in IL-23 and IL-17A and proinflammatory monocytosis and neutrophilia that precedes development of carotid artery thrombus formation. To examine whether targeted blockade of IL-23 or IL-17A in KC-Tie2 psoriasis mice improves cardiovascular outcomes, mice were treated systemically for 6 weeks with antibodies targeting IL-17A, IL-17RA, IL-12/23p40, or IL-23p19...
September 23, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28940259/efficacy-of-guselkumab-in-subpopulations-of-patients-with-moderate-to-severe-plaque-psoriasis-a-pooled-analysis-of-the-phase-3-voyage-1-and-voyage-2-studies
#10
K B Gordon, A Blauvelt, P Foley, M Song, Y Wasfi, B Randazzo, Y K Shen, Y You, C E M Griffiths
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 3 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...
September 22, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28935206/tlr7-8-agonists-stimulate-plasmacytoid-dendritic-cells-to-initiate-a-th17-deviated-acute-contact-dermatitis-in-humans
#11
Natalie Garzorz-Stark, Felix Lauffer, Linda Krause, Jenny Thomas, Anne Atenhan, Regina Franz, Sophie Roenneberg, Alexander Boehner, Manja Jargosch, Richa Batra, Nikola S Mueller, Stefan Haak, Christina Groß, Olaf Groß, Claudia Traidl-Hoffmann, Fabian J Theis, Carsten B Schmidt-Weber, Tilo Biedermann, Stefanie Eyerich, Kilian Eyerich
BACKGROUND: A standardized human model to study early pathogenic events in psoriasis is missing. Activation of Toll-like receptor 7/8 by topical application of imiquimod is the most commonly used mouse model of psoriasis. OBJECTIVE: To investigate the potential of a human imiquimod patch test model to resemble human psoriasis. METHODS: Imiquimod (Aldara® 5% cream) was applied twice a week onto the back of volunteers (n=18) and the development of skin lesions was monitored over a time period of four weeks...
September 18, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28921458/pharmacogenetics-and-pharmacogenomics-in-moderate-to-severe-psoriasis
#12
REVIEW
María C Ovejero-Benito, Ester Muñoz-Aceituno, Alejandra Reolid, Miriam Saiz-Rodríguez, Francisco Abad-Santos, Esteban Daudén
Pharmacogenetics is the study of variations in DNA sequence related to drug response. Moreover, the evolution of biotechnology and the sequencing of human DNA have allowed the creation of pharmacogenomics, a branch of genetics that analyzes human genes, the RNAs and proteins encoded by them, and the inter-and intra-individual variations in expression and function in relation to drug response. Pharmacogenetics and pharmacogenomics are being used to search for biomarkers that can predict response to systemic treatments, including those for moderate-to-severe psoriasis...
September 18, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28911642/lactobacillus-pentosus-gmnl-77-inhibits-skin-lesions-in%C3%A2-imiquimod-induced-psoriasis-like-mice
#13
Yi-Hsing Chen, Chieh-Shan Wu, Ya-Husan Chao, Chi-Chen Lin, Hui-Yun Tsai, Yi-Rong Li, Yi-Zhen Chen, Wan-Hua Tsai, Yu-Kuo Chen
Psoriasis, which is regarded as a T-cell-mediated chronic inflammatory skin disease, is characterized by hyperproliferation and poor differentiation of epidermal keratinocytes. In this study, we aimed to determine the in vivo effect of a potentially probiotic strain, Lactobacillus pentosus GMNL-77, in imiquimod-induced epidermal hyperplasia and psoriasis-like skin inflammation in BALB/c mice. Oral administration of L. pentosus GMNL-77 significantly decreased erythematous scaling lesions. Real-time polymerase chain reaction showed that treatment with L...
July 2017: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/28900461/effects-of-wannachawee-recipe-with-antipsoriatic-activity-on-suppressing-inflammatory-cytokine-production-in-hacat-human-keratinocytes
#14
Mingkwan Na Takuathung, Ariyaphong Wongnoppavich, Pornsiri Pitchakarn, Ampai Panthong, Parirat Khonsung, Natthakarn Chiranthanut, Noppamas Soonthornchareonnon, Seewaboon Sireeratawong
Psoriasis is a chronic inflammatory and immune-mediated skin disease. The pathogenesis involves T cells activation via the IL-23/Th17 axis. Conventional treatments of psoriasis have adverse events influencing patients' adherence. Wannachawee Recipe (WCR) has been effectively used as Thai folk remedy for psoriasis patients; however, preclinical evidence defining how WCR works is still lacking. This study defined mechanisms for its antiproliferation and anti-inflammatory effects in HaCaT cells. The cytotoxicity and antiproliferation results from SRB and CCK-8 assays showed that WCR inhibited the growth and viability of HaCaT cells in a concentration-dependent manner...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28899951/lowering-interleukin-12-activity-improves-myocardial-and-vascular-function-compared-with-tumor-necrosis-factor-a-antagonism-or-cyclosporine-in-psoriasis
#15
RANDOMIZED CONTROLLED TRIAL
Ignatios Ikonomidis, Evangelia Papadavid, George Makavos, Ioanna Andreadou, Maria Varoudi, Kostas Gravanis, Kostas Theodoropoulos, George Pavlidis, Helen Triantafyllidi, Paraskevi Moutsatsou, Christina Panagiotou, John Parissis, Efstathios Iliodromitis, John Lekakis, Dimitrios Rigopoulos
BACKGROUND: Interleukin (IL)-12 activity is involved in the pathogenesis of psoriasis and acute coronary syndromes. We investigated the effects of IL-12 inhibition on vascular and left ventricular (LV) function in psoriasis. METHODS AND RESULTS: One hundred fifty psoriasis patients were randomized to receive an anti-IL-12/23 (ustekinumab, n=50), anti-tumor necrosis factor-a (TNF-α; etanercept, n=50), or cyclosporine treatment (n=50). At baseline and 4 months post-treatment, we measured (1) LV global longitudinal strain, twisting, and percent difference between peak twisting and untwisting at mitral valve opening (%untwMVO) using speckle-tracking echocardiography, (2) coronary flow reserve, (3) pulse wave velocity and augmentation index, (4) circulating NT-proBNP (N-terminal pro-B-type natriuretic peptide), TNF-α, IL-6, IL-12, IL-17, malondialdehyde, and fetuin-a...
September 2017: Circulation. Cardiovascular Imaging
https://www.readbyqxmd.com/read/28898221/go-ahead-for-first-anti-il-23-mab-to-treat-psoriasis
#16
(no author information available yet)
No abstract text is available yet for this article.
September 11, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28895664/the-severe-and-acute-complications-of-the-biologics-in-psoriasis
#17
Elias Oussedik, Nupur U Patel, Devin R Cash, Angela S Gupta, Steven R Feldman
Biologic therapies have revolutionized the approach to immune-mediated diseases such as psoriasis. Due to their favorable safety profiles and excellent efficacy, biologic agents are considered the gold-standard for moderate-to-severe psoriasis. The aim of this paper is to saliently review the severe and acute complications of the Food and Drug Administration (FDA) approved biologic agents for psoriasis. Reviewed agents include tumor necrosis factor alpha (TNF-alpha) inhibitors (etanercept, infliximab, and adalimumab), interleukin 12/23 inhibitors (ustekinumab), and interleukin 17 inhibitors (secukinumab and ixekizumab)...
September 12, 2017: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
https://www.readbyqxmd.com/read/28895120/inflammation-treatment-progress-and-limitations
#18
EDITORIAL
Ingolf Cascorbi
There is an increasing understanding on the etiology of chronic immune-mediated inflammatory diseases such as inflammatory bowel disease (IBD), psoriasis, or rheumatoid arthritis. Large consortia contributed to the elucidation of the genetics, for instance, of IBD identifying a number of genes involved in innate mucosal defense and immune tolerance (most prominent, e.g., NOD2) and other related processes. For a number of such diseases, common genetic susceptibility loci were identified, suggesting overlapping immune response pathways, although there is no causality of single genetic traits...
October 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28887948/psoriasis-pathogenesis-and-the-development-of-novel-targeted-immune-therapies
#19
REVIEW
Jason E Hawkes, Tom C Chan, James G Krueger
Psoriasis is caused by a complex interplay between the immune system, psoriasis-associated susceptibility loci, autoantigens, and multiple environmental factors. Over the last 2 decades, research has unequivocally shown that psoriasis represents a bona fide T cell-mediated disease primarily driven by pathogenic T cells that produce high levels of IL-17 in response to IL-23. The discovery of the central role for the IL-23/type 17 T-cell axis in the development of psoriasis has led to a major paradigm shift in the pathogenic model for this condition...
September 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28887914/curcumin-attenuates-the-scurfy-induced-immune-disorder-a-model-of-ipex-syndrome-with-inhibiting-th1-th2-th17-responses-in-mice
#20
Gihyun Lee, Hwan-Suck Chung, Kyeseok Lee, Hyeonhoon Lee, Minhwan Kim, Hyunsu Bae
BACKGROUND: Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX) is a lethal autoimmune disease caused by mutations in the Foxp3 gene scurfin (scurfy). Immunosuppressive therapy for IPEX patients has been generally ineffective and has caused severe side effects, however curcumin has shown immune regulation properties for inflammatory diseases, such as rheumatoid arthritis, psoriasis, and inflammatory bowel diseases without side effects. OBJECTIVE: The aim of this study was to investigate whether curcumin would attenuate symptoms of IPEX in mouse model and would prolong its survival period...
September 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
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