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Il-23 and psoriasis

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https://www.readbyqxmd.com/read/28718898/exposure-to-biologic-therapies-during-conception-and-pregnancy-a-systematic-review
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28646393/the-changing-landscape-of-alopecia-areata-the-therapeutic-paradigm
#11
REVIEW
Yael Renert-Yuval, Emma Guttman-Yassky
Alopecia areata (AA), a prevalent inflammatory cause of hair loss, lacks FDA-approved therapeutics for extensive cases, which are associated with very poor rates of spontaneous hair regrowth and major psychological distress. Current treatments for severe cases include broad immune-suppressants, which are associated with significant adverse effects, precluding long-term use, with rapid hair loss following treatment termination. As a result of the extent of the disease in severe cases, topical contact sensitizers and intralesional treatments are of limited use...
June 23, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28642279/role-of-myd88-signaling-in-the-imiquimod-induced-mouse-model-of-psoriasis-focus-on-innate-myeloid-cells
#12
Sara Costa, Olivia Marini, Dalila Bevilacqua, Anthony L DeFranco, Baidong Hou, Silvia Lonardi, William Vermi, Pamela Rodegher, Anna Panato, Franco Tagliaro, Clifford A Lowell, Marco A Cassatella, Giampiero Girolomoni, Patrizia Scapini
Psoriasis is a chronic skin disease associated with deregulated activation of immune cells and keratinocytes. In this study, we used the imiquimod (IMQ)-induced mouse model of psoriasis to dissect better the contribution of hematopoietic and skin-resident stromal cells to psoriasis development. The comparison of disease development in mice carrying the hematopoietic cell-specific deletion of MyD88 (Myd88(fl/fl)Vav-cre(+) mice) with mice carrying the total MyD88 deficiency (Myd88(-/-) mice), we show that the progression of skin and systemic inflammation, as well as of epidermal thickening, was completely dependent on MyD88 expression in hematopoietic cells...
June 22, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28639011/guselkumab-for-the-treatment-of-psoriasis-a-review-of-phase-iii-trials
#13
REVIEW
Mio Nakamura, Katherine Lee, Caleb Jeon, Sahil Sekhon, Ladan Afifi, Di Yan, Kristina Lee, Tina Bhutani
INTRODUCTION: Interleukin (IL)-23 inhibitors are a new class of biologics currently undergoing clinical trials for the treatment of moderate-to-severe psoriasis. Phase III studies of guselkumab, an IL-23 receptor monoclonal antibody, are currently underway. METHODS: We summarize the available phase III results to date, establishing the efficacy and safety of guselkumab in patients with moderate-to-severe plaque psoriasis. RESULTS: Currently, there are available data of up to 48 weeks from two Phase III, multicenter, randomized, double-blind, placebo- and comparator-controlled clinical trials, VOYAGE 1 and VOYAGE 2...
June 21, 2017: Dermatology and Therapy
https://www.readbyqxmd.com/read/28634654/improvement-in-latent-variable-indirect-response-modeling-of-multiple-categorical-clinical-endpoints-application-to-modeling-of-guselkumab-treatment-effects-in-psoriatic-patients
#14
Chuanpu Hu, Bruce Randazzo, Amarnath Sharma, Honghui Zhou
Exposure-response modeling plays an important role in optimizing dose and dosing regimens during clinical drug development. The modeling of multiple endpoints is made possible in part by recent progress in latent variable indirect response (IDR) modeling for ordered categorical endpoints. This manuscript aims to investigate the level of improvement achievable by jointly modeling two such endpoints in the latent variable IDR modeling framework through the sharing of model parameters. This is illustrated with an application to the exposure-response of guselkumab, a human IgG1 monoclonal antibody in clinical development that blocks IL-23...
June 20, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28629323/fetal-death-in-utero-and-miscarriage-in-a-patient-with-crohn-s-disease-under-therapy-with-ustekinumab-case-report-and-review-of-the-literature
#15
C Venturin, S Nancey, P Danion, M Uzzan, M Chauvenet, C Bergoin, X Roblin, B Flourié, G Boschetti
BACKGROUND: Ustekinumab is a fully human monoclonal antibody against the p40 subunit of interleukin (IL) 12 and 23 which is involved in the pathogenesis of several inflammatory diseases. Ustekinumab is approved for psoriasis and psoriatic arthritis treatment and has been successfully evaluated in phase II and III trials for patients with Crohn's disease (CD). CASE PRESENTATION: We report here the case of a patient who became pregnant during treatment with ustekinumab for a refractory CD and which ended in miscarriage...
June 19, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28617942/withasteroid-b-from-d-metel-l-regulates-immune-responses-by-modulating-the-jak-stat-pathway-and-the-il-17-ror%C3%AE-t-il-10-foxp3-ratio
#16
Yang Su, Qiuhong Wang, Bingyou Yang, Lun Wu, Genhong Cheng, Haixue Kuang
Datura metel L. is a medicinal herb that contains withasteroids and has a wide range of biological activities. We isolated 7 withasteroids from the flowers of D. metel L(1) . and examined their ability to inhibit immune responses in vitro and in vivo. Among the withasteroids, B2(2) exhibited the strongest inhibitory effect on immune responses comparing B2 with other isolated compounds from D. metel L., including suppressing the differentiation of CD4(+3) T cells by inhibiting the expression and production of T cell lineage-specific master regulators and cytokines and directly suppressing the cytokine-induced JAK/STAT(4) signaling pathways...
June 15, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28602508/cyr61-ccn1-induces-ccl20-production-by-keratinocyte-via-activating-p38-and-jnk-ap-1-pathway-in-psoriasis
#17
Huidan Li, Haichuan Li, Rongfen Huo, Pinru Wu, Zhengyu Shen, Hui Xu, Baihua Shen, Ningli Li
BACKGROUND: Psoriasis is a common chronic skin disease characterized by epidermal hyperplasia and inflammation. Cysteine-rich angiogenic inducer 61 (Cyr61/CCN1) has recently been implicated in psoriasis pathogenesis by promoting keratinocyte activation. However, the mechanisms by which CCN1 enhances cutaneous inflammation are not fully understood. OBJECTIVE: In this study, we investigated the role of CCN1 on the expression of CCL20 in human keratinocyte. METHODS AND RESULTS: By double-label immunofluorescence staining, we first identified that the expression of CCN1 colocalized well with CCL20 production in the epidermis of psoriasis skin lesion...
June 1, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28592369/preliminary-study-of-histamine-h4-receptor-expressed-on-human-cd4-t-cells-and-its-immunomodulatory-potency-in-the-il-17-pathway-of-psoriasis
#18
Song Hee Han, Min Seok Hur, Min Jung Kim, Bo Mi Kim, Kyoung Woon Kim, Hae Rim Kim, Yong Beom Choe, Kyu Joong Ahn, Yang Won Lee
BACKGROUND: Previous studies have shown the expression of histamine H4 receptor (H4R) on CD4(+) T cells, especially human CD4(+) Th2-polarized T cells. OBJECTIVE: This study aimed to investigate the role of H4R on these effector T cells in psoriasis. METHODS: We enrolled three patients each with active psoriasis, inactive psoriasis, scalp seborrheic dermatitis, and three normal controls, and compared the basal expression of H4R mRNA in their peripheral blood CD4(+) T cells...
May 29, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28570274/tristetraprolin-expression-by-keratinocytes-controls-local-and-systemic-inflammation
#19
Mathieu Andrianne, Assiya Assabban, Caroline La, Denis Mogilenko, Delphine Staumont Salle, Sébastien Fleury, Gilles Doumont, Gaëtan Van Simaeys, Sergei A Nedospasov, Perry J Blackshear, David Dombrowicz, Stanislas Goriely, Laurye Van Maele
Tristetraprolin (TTP, encoded by the Zfp36 gene) regulates the mRNA stability of several important cytokines. Due to the critical role of this RNA-binding protein in the control of inflammation, TTP deficiency leads to the spontaneous development of a complex inflammatory syndrome. So far, this phenotype has been largely attributed to dysregulated production of TNF and IL‑23 by myeloid cells, such as macrophages or DCs. Here, we generated mice with conditional deletion of TTP in keratinocytes (Zfp36fl/flK14-Cre mice, referred to herein as Zfp36ΔEP mice)...
June 2, 2017: JCI Insight
https://www.readbyqxmd.com/read/28547750/management-of-long-term-therapy-with-biological-drugs-in-psoriatic-patients-with-latent-tuberculosis-infection-in-real-life-setting
#20
Andrea Conti, Stefano Piaserico, Paolo Gisondi, Giulia Odorici, Giovanna Galdo, Claudia Lasagni, Giovanni Pellacani
Psoriatic patients with latent tuberculosis infection (LTBI) need a prophylaxis before starting a treatment with biological drugs. The aim of this study is to investigate the safety and efficacy of prophylaxis of LTBI in psoriatic patients receiving long-term biological drugs. The study included 56 patients (42 male and 14 female) affected by moderate-to-severe psoriasis (mean PASI: 12.8 ± 6.9 SD) treated with anti-TNF-α and/or anti IL 12, 23 and/or anti-CD11 drugs with a diagnosis of LTBI. LTBI diagnosis was based on tuberculin skin test and/or QuantiFERON TB Gold test positivity and chest X-ray suggestive, without clinical, or microbiological evidence of active disease...
May 26, 2017: Dermatologic Therapy
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