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Il-23 and psoriasis

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https://www.readbyqxmd.com/read/28819723/guselkumab-first-global-approval
#1
Anthony Markham
Guselkumab (Tremfya™) is a human monoclonal IgG1λ antibody being developed by Janssen Biotech, Inc. that has been approved in the USA as a treatment for moderate-to-severe plaque psoriasis. Guselkumab inhibits the binding of interleukin 23 (IL-23) to its cell surface receptor, disrupting the type 17 helper T cell/IL-17 pathway. This article summarizes the milestones in the development of guselkumab leading to this first approval for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy...
August 17, 2017: Drugs
https://www.readbyqxmd.com/read/28791896/biologics-that-inhibit-the-th17-pathway-and-related-cytokines-to-treat-inflammatory-disorders
#2
Anna Balato, Emanuele Scala, Nicola Balato, Giuseppina Caiazzo, Roberta Di Caprio, Giuseppe Monfrecola, Annunziata Raimondo, Serena Lembo, Fabio Ayala
Advances in the understanding of TNF-α and IL-17 synergistic functions have recently led to the concept that patients who do not respond or who respond inadequately to TNF-α inhibitors may have IL-17-driven diseases, opening up the way for a new class of therapeutic development: Th17-inhibitors. Areas covered: In this review, the authors discuss the central role that the IL-23/Th17 axis plays in the pathogenesis of several inflammatory diseases, such as psoriasis, highlighting its position as a relevant therapeutic target...
August 9, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28780985/9-19-cycloartenol-glycoside-g3-from-cimicifuga-simplex-regulates-immune-responses-by-modulating-th17-treg-ratio
#3
Yang Su, Lun Wu, Guangrui Mu, Qiuhong Wang, Bingyou Yang, Genhong Cheng, Haixue Kuang
Cimicifuga simplex is a medicinal herb which has a wide range of biological activities. We isolated seven 9,19-cycloartenol glycosides from the roots of C. simplex, and among the glycosides, G3 exhibited the strongest inhibitory effect on immune responses, including suppressing the differentiation of CD(4+) T cells and directly suppressing the cytokine-induced JAK/STAT signaling pathways. In the IL-23-induced mouse ear model of skin disease, G3 repressed disease development by inhibiting the expression of pro-inflammatory mediators in murine ear skin...
July 27, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28770513/selective-interleukin-23-p19-inhibition-another-game-changer-in-psoriasis-focus-on-risankizumab
#4
Tiago Torres
The history of psoriasis treatment has been marked by several milestones. Corticosteroids, cyclosporine, tumor necrosis factor alpha (TNF-α) inhibitors and, more recently, interleukin (IL)-17A inhibitors have revolutionized the treatment of psoriasis, each in its own way and time. The IL-23/IL-17 axis is currently considered to be crucial in the pathogenesis of psoriasis and selective IL-23p19 inhibition may bring several advantages with respect to IL-12/23p40 inhibition, or distal blockade of IL-17A or its receptor...
August 2, 2017: Drugs
https://www.readbyqxmd.com/read/28761880/therapeutic-effects-of-methanol-extract-from-euphorbia-kansui-radix-on-imiquimod-induced-psoriasis
#5
Soo Jeong Kim, Ye Won Jang, Kyung Eun Hyung, Da Kyoung Lee, Kee Hyeob Hyun, So-Young Park, Eon-Sub Park, Kwang Woo Hwang
The roots of Euphorbia kansui, which belong to the family Euphorbiaceae, have been used as a traditional medicine for the treatment of various diseases such as diabetes, ascites, and leukemia. Recently, it was reported that the methylene chloride fraction of E. kansui radix (EKC) regulated the differentiation of Th17 cells and alleviated the symptoms of Th17-related inflammatory bowel disease. Imiquimod (IMQ), a TLR7/8 agonist, has been used to induce psoriasis in a mouse model. In this study, we evaluated the effect of EKC in an IMQ-induced psoriasis model...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28761295/the-clinical-profile-of-patients-with-psoriasis-in-korea-a-nationwide-cross-sectional-study-epi-psode
#6
Hae Jun Song, Chul Jong Park, Tae Yoon Kim, Yong Beom Choe, Seok-Jong Lee, Nack In Kim, Jae We Cho, Jie Hyun Jeon, Min Soo Jang, Jai Il Youn, Myung Hwa Kim, Joonsoo Park, Ki Ho Kim, Byung Soo Kim, Sang Woong Youn, Joo-Heung Lee, Min-Geol Lee, Sung Ku Ahn, Young Ho Won, Seok Kweon Yun, Bong Seok Shin, Seong Jun Seo, Ji Yeoun Lee, Kwang Joong Kim, Young Suck Ro, Youngdoe Kim, Dae Young Yu, Jee-Ho Choi
BACKGROUND: Psoriasis is an immune-mediated, chronic inflammatory disease affecting multiple aspects of patients' lives. Its epidemiology varies regionally; however, nationwide epidemiologic data on psoriasis depicting profile of Korean patients has not been available to date. OBJECTIVE: To understand nationwide epidemiologic characteristics and clinical features of adult patients with psoriasis visited university hospitals in Korea. METHODS: This multicenter, non-interventional, cross-sectional study recruited 1,278 adult patients with psoriasis across 25 centers in Korea in 2013...
August 2017: Annals of Dermatology
https://www.readbyqxmd.com/read/28738533/mir-200a-expression-in-cd4-t-cells-correlates-with-the-expression-of-th17-treg-cells-and-relevant-cytokines-in-psoriasis-vulgaris-a-case-control-study
#7
Xiao-Yan Wang, Xing-Yu Chen, Jun Li, Hong-Ying Zhang, Juan Liu, Le-Dong Sun
The main aim of this study is to investigate the underlying relationship shared between microRNA-200a (miR-200a) and its link to concentrations of Th17 and Treg cells, mRNA expressions of their specific transcription factors retinoic acid-related orphan receptor γt (RORγt) and head box protein 3 (FOXP3) and relevant cytokines in patients with psoriasis vulgaris (PV). A total of 189 patients previously diagnosed with PV were selected as the experimental group, whilst 109 healthy individuals as the control group...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28736282/imiquimod-induced-psoriasis-like-inflammation-in-differentiated-human-keratinocytes-its-evaluation-using-curcumin
#8
Sandeep R Varma, Thiyagarajan O Sivaprakasam, Abheepsa Mishra, Sunil Prabhu, Rafiq M, Rangesh P
Psoriasis is considered to be a systemic disease of immune dysfunction. It is still unclear what triggers the inflammatory cascade associated with psoriasis but recent evidences suggest the vital role of IL-23/IL-17A cytokine axis in etiology of psoriasis. Several studies have been conducted in psoriatic-like animal models but ethical issues and complexity surrounding it halts the screening of new anti-psoriatic drug candidates. Hence, in this study, we developed a new in-vitro model for psoriasis using imiquimod (IMQ) induced differentiated HaCaT cells which could be used for screening of new anti-psoriatic drug candidates...
July 21, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28732748/controlling-the-pro-inflammatory-function-of-6-sulfo-lacnac-slan-dendritic-cells-with-dimethylfumarate
#9
Stephanie Oehrl, Florina Olaru, Anja Kunze, Michael Maas, Silvia Pezer, Marc Schmitz, Knut Schäkel
BACKROUND: The fumaric acid ester (FAE) dimethylfumarate (DMF) is a small molecule immunomodulator successfully used for the treatment of psoriasis and multiple sclerosis (MS). DMF is thought to inhibit pathogenic immune responses with Th17/Th1T cells, and IL-23/IL-12 producing dendritic cells (DCs). 6-sulfo LacNAc expressing dendritic cells (slanDCs) are a human pro-inflammatory cell type found frequently among the infiltrating leukocytes in skin lesions of psoriasis and brain lesions of MS...
June 24, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28730954/evaluation-of-in-vitro-anti-psoriatic-activity-of-a-novel-polyherbal-formulation-by-multiparametric-analysis
#10
Nadav Shraibom, Alka Madaan, Vidushi Joshi, Ritu Verma, Anika Chaudhary, Gautam Mishra, Anshumali Awasthi, Anu Taneja Singh, Manu Jaggi
The beneficial role of traditional herbal medicines in the treatment of inflammatory skin disorders has been widely reported. Psoriasis is characterized by uncontrolled hyper-proliferation of keratinocytes, disturbed apoptosis, over-secretion of inflammatory cytokines and angiogenic factors. We have developed a novel aqueous polyherbal formulation (SIRB-001) consisting of 3 herbs; Rheum palmatum L., Rehmannia glutinosa Libosch and Lonicera Japonica in the ratio 1:1:3. SIRB-001 has demonstrated efficacious effects in psoriasis patients...
July 20, 2017: Anti-inflammatory & Anti-allergy Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28718898/exposure-to-biologic-therapies-during-conception-and-pregnancy-a-systematic-review
#11
E M Pottinger, R T Woolf, L S Exton, A D Burden, C Nelson-Piercy, C H Smith
Biologic therapies are effective treatments for psoriasis and are often used in women of childbearing age. To evaluate the safety of biologic therapy in conception and/or pregnancy, we have performed a systematic review of Pubmed, MEDLINE, EMBASE and Cochrane databases for multivariable adjusted studies of women exposed to biologic therapy relevant to the treatment of psoriasis during conception and/or pregnancy. We identified four population-based cohort studies involving 1300 women exposed to TNF-α inhibitors (TNFi) 3 months prior to or during the first 3 months of pregnancy...
July 18, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28712395/-inhibitory-effect-of-bispecific-antibody-targeting-il-12-p40-and-tnf-%C3%AE-simultaneously-on-psoriasis-in-mice
#12
Pin Xu, Ni Xie, Caiguo Ye
Objective To construct bispecific antibodies, which can block interleukin 12 (IL-12)/IL-23 p40 subunit and tumor necrosis factor α (TNF-α) simultaneously, and identify their biological function and inhibitory effect on psoriasis formation in mice. Methods Based on the sequences of adalimumab and ustekinumab, three kinds of bispecific antibodies were designed, named BiAU003, BiAU022 and BiAU023. The specificity and binding capacity of bispecific antibodies were determined by ELISA. After co-treated with bispecific antibodies and TNF-α, the level of endothelial leukocyte adhesion molecule-1 (ELMA-1) labeled with fluorescein isothiocyanate (FITC) in human umbilical vein endothelial cells (HUVECs) were examined by flow cytometry...
July 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28697222/injection-site-reactions-to-biologic-agents-used-in-psoriasis-and-psoriatic-arthritis
#13
Meagan-Helen Henderson Berg, Daniel Carrasco
<p>Psoriasis is a chronic inflammatory cutaneous disease that affects 2-3% of the general population. Up to 30% of patients with psoriasis also develop psoriatic arthritis, a chronic inflammatory and progressive arthritis. Although their precise pathogeneses remain unclear, psoriasis and psoriatic arthritis involve altered expression of proinflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-12, IL-17, IL-22, and IL-23. The development of biologic agents that target these cytokines has greatly improved the treatment of psoriatic disease...
July 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28696418/associations-between-functional-polymorphisms-and-response-to-biological-treatment-in-danish-patients-with-psoriasis
#14
N D Loft, L Skov, L Iversen, R Gniadecki, T N Dam, I Brandslund, H J Hoffmann, M R Andersen, R B Dessau, A C Bergmann, N M Andersen, P S Andersen, S Bank, U Vogel, V Andersen
Biological agents including anti-tumor necrosis factor (anti-TNF; adalimumab, infliximab, etanercept) and anti-interleukin-12/13 (IL12/23; ustekinumab) are essential for treatment of patients with severe psoriasis. However, a significant proportion of the patients do not respond to a specific treatment. Pharmacogenetics might be a way to predict treatment response. Using a candidate gene approach, 62 mainly functional single-nucleotide polymorphisms (SNPs) in 44 different genes were evaluated in 478 Danish patients with psoriasis undergoing 376 series of anti-TNF treatment and 230 series of ustekinumab treatment...
July 11, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28674347/cardiovascular-and-metabolic-diseases-comorbid-with-psoriasis-beyond-the-skin
#15
Masutaka Furue, Gaku Tsuji, Takahito Chiba, Takafumi Kadono
A close association of systemic inflammation with cardiovascular diseases and metabolic syndrome is recently a popular topic in medicine. Psoriasis is a chronic inflammatory skin disease with a prevalence of approximately 0.1-0.5% in Asians. It is characterized by widespread scaly erythematous macules that cause significant physical and psychological burdens for the affected individuals. The accelerated inflammation driven by the TNF-α/IL-23/IL-17A axis is now known to be the major mechanism in the development of psoriasis...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28667777/review-of-phase-iii-trial-data-on-il-23-inhibitors-tildrakizumab-and-guselkumab-for-psoriasis
#16
REVIEW
M Amin, K Darji, D J No, J J Wu
BACKGROUND: The development of monoclonal antibodies targeting IL-12 and IL-23 has enhanced the therapeutic options available for psoriasis patients. Recent research suggests that IL-23 alone plays a role in the pathogenesis of psoriasis. OBJECTIVE: The objective was to review the phase III clinical trial data for the anti-IL-23 agents in order to evaluate the safety and efficacy profile of each agent. METHODS: We reviewed the results of the phase III clinical trials for the anti-IL-23 agents tildrakizumab and guselkumab...
July 1, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28664285/-psoriasis-vs-psoriatic-arthritis-similarities-and-differences-in-the-pathophysiology
#17
T Pap, C Sunderkötter
Psoriasis is a chronic inflammatory skin disease with genetic and (auto)immunological backgrounds. Up to 30% of patients with psoriasis also develop a mostly oligoarticular arthritis with spinal involvement that is termed psoriatic arthritis (PsA) and shows a specific joint pattern which differs from that of rheumatoid arthritis (RA). Both Psa and psoriasis share a common main axis, the interleukin (IL) 23/IL17 pathway as well as major overlaps in the functions of tumor necrosis factor alpha (TNFalpha)...
June 29, 2017: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/28658319/hypomorphic-a20-expression-confers-susceptibility-to-psoriasis
#18
Anri Aki, Miyuki Nagasaki, Barbara Ann Malynn, Averil Ma, Takashi Kagari
Psoriasis is a common inflammatory skin disease that affects approximately 1% of the population worldwide. Tumor necrosis factor-alpha-induced protein 3 (TNFAIP3) gene polymorphisms have been strongly associated with psoriasis susceptibility. In this study, we investigate how TNFAIP3, also known as A20, may regulate psoriasis susceptibility. We found that haplo-insufficient A20+/- mice develop severe toll-like receptor (TLR)-induced skin inflammation compared to wild type mice owing to amplified production of interleukin (IL)-17 and IL-23...
2017: PloS One
https://www.readbyqxmd.com/read/28653490/the-role-of-il-23-and-the-il-23-th-17-immune-axis-in-the-pathogenesis-and-treatment-of-psoriasis
#19
REVIEW
G Girolomoni, R Strohal, L Puig, H Bachelez, J Barker, W H Boehncke, J C Prinz
Psoriasis is a chronic, immune-mediated disease affecting more than 100 million people worldwide and up to 2.2% of the UK population. The etiology of psoriasis is thought to originate from an interplay of genetic, environmental, infectious, and lifestyle factors. The manner in which genetic and environmental factors interact to contribute to the molecular disease mechanisms has remained elusive. However, the interleukin 23 (IL-23)/T-helper 17 (TH 17) immune axis has been identified as a major immune pathway in psoriasis disease pathogenesis...
June 27, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28650001/brodalumab-the-first-anti-il-17-receptor-agent-for-psoriasis
#20
L Puig
Psoriasis is a chronic immune-mediated inflammatory skin disease in which the alteration of the interleukin-23 (IL-23)/IL-17 cytokine axis appears to be crucial from a pathogenetic perspective. This has been confirmed by the efficacy of monoclonal antibodies blocking IL-17A, such as secukinumab and ixekizumab. Brodalumab is a human anti-IL-17 receptor A (IL-17RA) monoclonal antibody that inhibits the biological activity of IL-17A, IL-17F and other IL-17 isoforms, and has been approved (210 mg s.c. at weeks 0, 1, 2 and every 2 weeks thereafter) for the treatment of psoriasis vulgaris, psoriatic arthritis, pustular psoriasis and psoriatic erythroderma in Japan (Lumicef)...
May 2017: Drugs of Today
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