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Il-23 and psoriasis

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https://www.readbyqxmd.com/read/29470778/guselkumab-for-the-treatment-of-psoriasis
#1
REVIEW
Álvaro Machado, Tiago Torres
Psoriasis is a common, chronic, immune-mediated, inflammatory skin disease with systemic involvement and significant impact on patients' quality of life. Several biologic treatments have been developed in recent decades, such as tumor necrosis factor (TNF)-α inhibitors, a non-selective interleukin (IL)-23 inhibitor (ustekinumab, which also inhibits IL-12), and-most recently-IL-17 inhibitors. Guselkumab is a novel biological therapy that selectively targets IL-23 and is the first-in-class selective IL-23 inhibitor approved to treat moderate-to-severe plaque psoriasis...
February 22, 2018: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/29464437/cutaneous-manifestations-of-reactions-to-biologics
#2
REVIEW
Iris M Otani, Amy S Levin, Aleena Banerji
PURPOSE OF REVIEW: The goal of this paper is to review the major adverse cutaneous reactions that have been reported to the most commonly used biologics. RECENT FINDINGS: Anti-TNF agents and immune checkpoint inhibitors have significant, immune-mediated cutaneous manifestations that can necessitate discontinuation. Anti-TNF agents, IL-6 inhibitors, and IL-12/23 inhibitors can paradoxically cause psoriasis flares or unmask previously undiagnosed psoriasis. IL-17 inhibitors are unique in increasing risk for Candida infections...
February 21, 2018: Current Allergy and Asthma Reports
https://www.readbyqxmd.com/read/29448914/-express-quantitative-evaluation-to-efficacy-and-safety-of-therapies-for-psoriasis-a-network-meta-analysis
#3
Jingjing Lv, Dongmei Zhou, Yan Wang, Jingxia Zhao, Zhaoxia Chen, Jinchao Zhang, Tingting Di, Jing Hu, Bo Li, Ping Li
Therapies treating psoriasis can be categorized into 5 classes according to their mechanism: anti-metabolites (AM), anti-interleukin-12/23 agents (anti-IL 12/23), anti-interleukin-17 agents (anti-IL 17), anti-T-cell agent (ANT), and anti- tumor necrosis factor-α agent (anti-TNF-α). This network meta-analysis (NMA) aimed to give a quantitative and systemic evaluation of safety and efficacy for above five kinds of therapies. Odd ratios (ORs) and mean differences (MDs) were calculated to evaluate binary and continuous outcomes, respectively...
January 1, 2018: Molecular Pain
https://www.readbyqxmd.com/read/29441315/targeting-il-23-in-psoriasis-current-perspectives
#4
REVIEW
Christina Fotiadou, Elizabeth Lazaridou, Eleni Sotiriou, Demetrios Ioannides
The recent advances in the understanding of psoriasis pathogenesis have clarified the pivotal role of interleukin (IL)-23. It is a heterodimeric cytokine consisting of two subunits, the unique p19 and the p40, which are shared with IL-12. The basic role of IL-23 in psoriasis is the activation and maintenance of the T-helper 17 pathway. New research findings indicate that IL-23 is more important than IL-12 in the pathogenesis of psoriasis. Based on that background, the selective targeting of the IL-23p19 subunit emerged as an attractive therapeutic option and led to the development of a new category of biologic agents...
2018: Psoriasis: Targets and Therapy
https://www.readbyqxmd.com/read/29439608/a-review-of-ustekinumab-in-the-treatment-of-psoriatic-arthritis
#5
Janet Roberts, Darren D O'Rielly, Proton Rahman
Psoriatic arthritis is an inflammatory arthritis associated with psoriasis. The IL-23/IL-17 axis is an important pathway in the development of psoriatic disease. Ustekinumab is a fully human monoclonal IgG1 antibody that binds to the p40 subunit of IL-12 and IL-23, which, in turn, inhibits downstream signaling pathways. PSUMMIT-1 and PSUMMIT-2 are two pivotal Phase III trials demonstrating global improvement in primary and secondary outcomes including inhibition of radiographic progression. Therapeutic benefit of ustekinumab for synovitis appears independent of previous disease modifying antirheumatic disease or anti-TNF exposure...
February 14, 2018: Immunotherapy
https://www.readbyqxmd.com/read/29438576/shifting-the-focus-the-primary-role-of-il-23-in-psoriasis-and-other-inflammatory-disorders
#6
REVIEW
M J Gooderham, K A Papp, C W Lynde
Insights into the pathophysiology of autoimmune inflammatory diseases including psoriasis have advanced considerably in recent years, and in parallel, so too have the available treatment options. Current clinical paradigms for the treatment of psoriasis have evolved to include targeted biologic therapies, starting with tumor necrosis factor-alpha (TNF-α) inhibitors and later, agents targeting interleukin (IL)-12/23 and IL-17. The most recent evidence suggests that IL-23 might be an even more potent target for the effective treatment of psoriasis and other autoimmune inflammatory disorders...
February 13, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29432814/pi3k-akt-mtor-activation-and-autophagy-inhibition-plays-a-key-role-in-increased-cholesterol-during-il-17a-mediated-inflammatory-response-in-psoriasis
#7
Pallavi Varshney, Neeru Saini
Psoriasis is an immune-mediated inflammatory disease of the skin. Previous studies including ours have shown that IL-17A plays a major role in its pathogenesis; however, its precise molecular mechanism of action is not well understood. Cytokines like TNF α and IL-23 are also important in mediating the disease and some studies have also reported autophagy as a novel mechanism by which cytokines controls the immune response. Herein, we investigated the effect of IL-17A on autophagy and reveal crosstalk between autophagy and cholesterol signaling in keratinocytes...
February 9, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29425183/role-of-the-il-23-il-17-axis-in-psoriasis-and-psoriatic-arthritis-the-clinical-importance-of-its-divergence-in-skin-and-joints
#8
REVIEW
Marie-Astrid Boutet, Alessandra Nerviani, Gabriele Gallo Afflitto, Costantino Pitzalis
Psoriasis is a chronic systemic inflammatory disease causing erythematosus and scaly skin plaques; up to 30% of patients with psoriasis develop Psoriatic Arthritis (PsA), which is characterised by inflammation and progressive damage of the peripheral joints and/or the spine and/or the entheses. The pathogenic mechanisms driving the skin disorder in psoriasis and the joint disease in PsA are sustained by the activation of inflammatory pathways that can be overlapping, but also, at least partially, distinct. Cytokines members of the IL-23/IL-17 family, critical in the development of autoimmunity, are abundantly expressed within the cutaneous lesions but also seem to be involved in chronic inflammation and damage of the synovium though, as it will be here discussed, not in all patients...
February 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29424306/biologic-therapy-in-psoriasis-part-i-efficacy-and-safety-of-tumor-necrosis-factor-%C3%AE-inhibitors
#9
A Campanati, E Molinelli, G Ganzetti, V Brisigotti, A Offidani
BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory disorder, with an estimated global prevalence of 2-3%. Psoriasis is associated with an impaired health-related quality of life and a substantial economic burden. Biologics, which target the pathways involved in the pathogenesis of psoriasis, represent an established therapeutic approach for moderate-to-severe plaque psoriasis, with remarkable efficacy and safety profile extensively examined and monitored. METHODS: Biological therapies currently available can be divided into three main categories: the TNFα antagonists (infliximab, adalimumab, etanercept, golimumab, certolizumab pegol), the interleukin (IL)-12/23 monoclonal antibody (ustekinumab), and IL-17 inhibitor (secukinumab, ixekizumab)...
February 9, 2018: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/29420255/development-and-translational-application-of-a-minimal-physiologically-based-pharmacokinetic-mpbpk-model-for-a-monoclonal-antibody-mab-against-interleukin-23-il-23-in-il-23-induced-psoriasis-like-psl-mice
#10
Xi Chen, Xiling Jiang, Rajitha Janssen R D Doddareddy, Brian Geist, Thomas McIntosh, William J Jusko, Honghui Zhou, Weirong Wang
The IL-23/Th17/IL-17 immune pathway has been identified to play an important role in the pathogenesis of psoriasis. Many therapeutic proteins targeting IL-23 or IL-17 are currently under development for the treatment of psoriasis. In the present study, a mechanistic PK/PD study was conducted to assess the target-binding and disposition kinetics of a monoclonal antibody (mAb), CNTO 3723, and its soluble target, mouse IL-23, in an IL-23-induced psoriasis-like (PsL) mouse model. A minimal physiologically-based pharmacokinetic (mPBPK) model with target-mediated drug disposition (TMDD) features was developed to quantitatively assess the kinetics and interrelationship between CNTO 3723 and exogenously administered, recombinant mouse IL-23 (rmIL-23) in both serum and lesional skin site...
February 2, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29416693/serum-levels-of-adipokines-and-cytokines-in-psoriasis-patients-a-systematic-review-and-meta-analysis
#11
Fan Bai, Wen Zheng, Yan Dong, Juan Wang, Malgorzata A Garstka, Ruilian Li, Jingang An, Huiqun Ma
Purpose: To evaluate the association of serum levels of adipokines and cytokines with psoriasis. Materials and Methods: A comprehensive literature search was performed in PubMed, ScienceDirect and Web of Science for the available relevant studies published before December 1, 2016. Differences in serum marker levels between patients and controls were pooled as standardized mean differences (SMDs) with 95% confidence interval to combine the effect estimations. We also conducted stratified analysis, meta-regression analysis and sensitivity analysis...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29405437/studying-the-effect-of-systemic-and-biological-drugs-on-intima-media-thickness-in-patients-suffering-from-moderate-and-severe-psoriasis
#12
Antonio Martinez-Lopez, Gonzalo Blasco-Morente, Israel Perez-Lopez, Jesus Tercedor-Sanchez, Salvador Arias-Santiago
BACKGROUND: Psoriasis has been related to a large number of cardiovascular risk factors such as hypertension, diabetes mellitus and arteriosclerosis. The increased carotid intima-media thickness (IMT) could be considered to be a marker of generalized arteriosclerosis. OBJECTIVE: To assess the effect of systemic and biological drugs on psoriatic patients' carotid IMT. METHODS: A prospective study was performed. We studied 53 patients with moderate and severe psoriasis from our psoriasis dermatological unit, analyzing lipid and glucose metabolism and performing a carotid IMT sonography before introduction of systemic and biological drugs...
February 6, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29395738/th17%C3%A2-cells-%C3%AE-%C3%AE-t-cells-and-their-interplay-in-eae-and-multiple-sclerosis
#13
REVIEW
Aoife M McGinley, Sarah C Edwards, Mathilde Raverdeau, Kingston H G Mills
Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS) that shares many features with the human disease. This review will focus on the role of IL-17-secreting CD4 and γδ T cells in EAE and MS, the plasticity of Th17 cells in vivo and the application of these findings to the understating of the pathogenesis and the development of new treatments for MS. There is convincing evidence that IL-17-secreting CD4 T cells (Th17 cells) and IL-17-secreting γδ T cells play a critical pathogenic role in central nervous system (CNS) inflammation in EAE and MS...
January 21, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29364440/how-relevant-are-vascular-endothelial-growth-factor-and-intercellular-adhesion-molecule-in-the-systemic-capillary-leak-syndrome-of-psoriasis
#14
Aline Lopes Bressan, Daniele Pereira, Paula Mota Medeiros, Sueli Carneiro, Luna Azulay-Abulafia
Psoriasis is a chronic disease, characterized by erythematous scaly lesions, presented in eight different forms: plaques, guttate, pustular, erythrodermic, inverse, nail and scalp psoriasis, and psoriatic arthritis. Its development depends on genetic factors, external stimulus and immune response alteration.1 Proinflammatory cytokines such as TNF-alpha, IL-12 and 23 may also be involved. In the worst cases, systemic complications linked to endothelial alterations may occur. A literature review was conducted for a better understanding of what roles VEGF (vascular endothelial growth factor) and ICAM-1 (intercellular adhesion molecule) have, among other cytokines, in systemic capillary leak syndrome, involved in erythrodermic and pustular psoriasis, the most unstable forms of the disease...
November 2017: Anais Brasileiros de Dermatologia
https://www.readbyqxmd.com/read/29349534/psoriasis-from-pathogenesis-to-targeted-therapies
#15
REVIEW
Curdin Conrad, Michel Gilliet
Over the last decade, the management of psoriasis has witnessed a paradigm shift. Thanks to the increasing knowledge about the pathogenesis of psoriasis, targeted treatments with monoclonal antibodies have been developed. These antibodies, which target the pathogenic TNF/IL-23/IL-17-pathway, were shown to be safe and efficacious in the management of most patients with moderate to severe chronic plaque psoriasis. Recently, molecular and genetic studies in pustular and erythrodermic psoriasis have identified additional inflammatory pathways, providing evidence that psoriasis is a heterogeneous disease and highlighting the requirement for personalized disease characterization for treatment optimization...
January 18, 2018: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/29344110/anti-interleukin-and-interleukin-therapies-for-psoriasis-current-evidence-and-clinical-usefulness
#16
REVIEW
Ya-Chu Tsai, Tsen-Fang Tsai
Anti-interleukin (IL) therapies have emerged as a major treatment for patients with moderate-to-severe psoriasis. This article reviews the up-to-date results of pivotal clinical trials targeting the interleukins used for the treatment of psoriasis, including IL-1, IL-2, IL-6, IL-8, IL-10, IL-12, IL-17, IL-20, IL-22, IL-23, IL-36 and bispecific biologics IL-17A/tumor necrosis factor alpha (TNF-α). Cytokines involved in the circuits of psoriasis inflammation without ongoing clinical trials are also mentioned (IL-9, IL-13, IL-15, IL-16, IL-18, IL-19, IL-21, IL-24, IL-27, IL-33, IL-35, IL-37, and IL-38)...
November 2017: Therapeutic Advances in Musculoskeletal Disease
https://www.readbyqxmd.com/read/29341192/population-pharmacokinetic-modeling-of-guselkumab-a-human-igg1%C3%AE-monoclonal-antibody-targeting-il-23-in-patients-with-moderate-to-severe-plaque-psoriasis
#17
Zhenling Yao, Chuanpu Hu, Yaowei Zhu, Zhenhua Xu, Bruce Randazzo, Yasmine Wasfi, Yang Chen, Amarnath Sharma, Honghui Zhou
Psoriasis is a common inflammatory skin disorder that requires chronic treatment and is associated with multiple comorbidities. Guselkumab, a human immunoglobulin-G1-lambda monoclonal antibody, binds to interleukin-23 with high specificity and affinity and is effective in treating moderate to severe plaque psoriasis. As part of the guselkumab psoriasis clinical trial program, using a confirmatory approach, a population pharmacokinetics (PopPK) model was established using 13 014 PK samples from 1454 guselkumab-treated patients across 3 phase 2/3 trials...
January 17, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29339075/up-regulated-lncrna-msx2p1-promotes-the-growth-of-il-22-stimulated-keratinocytes-by-inhibiting-mir-6731-5p-and-activating-s100a7
#18
Meng Qiao, Ronghua Li, Xintong Zhao, Jianjun Yan, Qing Sun
Competitive endogenous RNAs (ceRNAs) regulate RNA transcripts by competing for shared miRNAs and play critical roles in disease development. Psoriasis is a long-lasting, recurring chronic inflammatory skin disease characterized by hyperproliferation of keratinocytes. The keratinocyte response is triggered by the activation of inflammatory cytokines, like interleukin-22 (IL-22). We used lncRNA array analysis to detect differentially expressed lncRNAs in skin (HaCaT) cells treated with or without IL-22. We used hematoxylin and eosin (H&E) staining to determine the pathological changes in skin cells and immunohistochemistry to evaluate the expression of S100A7...
January 12, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29327456/discovery-and-characterization-of-cd12681-a-potent-ror%C3%AE-inverse-agonist-preclinical-candidate-for-the-topical-treatment-of-psoriasis
#19
Gilles Ouvry, Nicolas Atrux-Tallau, Franck Bihl, Aline Bondu, Claire Bouix-Peter, Isabelle Carlavan, Olivier Christin, Marie-Josée Cuadrado, Claire Defoin-Platel, Sophie Deret, Denis Duvert, Christophe Feret, Mathieu Forissier, Jean-François Fournier, David Froude, Fériel Hacini-Rachinel, Craig Steven Harris, Catherine Hervouet, Hélène Huguet, Guillaume Lafitte, Anne-Pascale Luzy, Branislav Musicki, Danielle Orfila, Benjamin Ozello, Coralie Pascau, Jonathan Pascau, Véronique Parnet, Guillaume Peluchon, Romain Pierre, David Piwnica, Catherine Raffin, Patricia Rossio, Delphine Spiesse, Nathalie Taquet, Etienne Thoreau, Rodolphe Vatinel, Emmanuel Vial, Laurent François Hennequin
With possible implications in multiple autoimmune diseases, the retinoic acid receptor-related orphan receptor RORγ has become a very sought-after target in the pharmaceutical industry. Herein are described the efforts to identify a potent RORγ inverse agonist compatible with topical application for the treatment of skin diseases. These efforts culminated with the discovery of CD12681 (compound 14; N-(2,4-dimethylphenyl)-N-isobutyl-2-oxo-1-((tetrahydro-2H-pyran-4-yl)methyl)-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide), a potent inverse agonist with in vivo activity in an IL-23 induced skin inflammation model in mouse...
January 12, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29316717/scanning-the-immunopathogenesis-of-psoriasis
#20
REVIEW
Andrea Chiricozzi, Paolo Romanelli, Elisabetta Volpe, Giovanna Borsellino, Marco Romanelli
Psoriasis is a chronic inflammatory skin disease, the immunologic model of which has been profoundly revised following recent advances in the understanding of its pathophysiology. In the current model, a crosstalk between keratinocytes, neutrophils, mast cells, T cells, and dendritic cells is thought to create inflammatory and pro-proliferative circuits mediated by chemokines and cytokines. Various triggers, including recently identified autoantigens, Toll-like receptor agonists, chemerin, and thymic stromal lymphopoietin may activate the pathogenic cascade resulting in enhanced production of pro-inflammatory and proliferation-inducing mediators such as interleukin (IL)-17, tumor necrosis factor (TNF)-α, IL-23, IL-22, interferon (IFN)-α, and IFN-γ by immune cells...
January 8, 2018: International Journal of Molecular Sciences
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