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https://www.readbyqxmd.com/read/28790099/gsk2586184-a-jak1-selective-inhibitor-in-two-patients-with-ulcerative-colitis
#1
Leonie C S De Vries, Valerie J Ludbrook, Kirsty J Hicks, Geert R D'Haens
Tofacitinib, a non-selective Janus kinase (JAK) inhibitor, is effective in inducing clinical and endoscopic remission in patients with active ulcerative colitis (UC). Tofacitinib inhibits cytokine signalling through blockade of JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2). Adverse events including neutropenia and anaemia resulting from JAK2 inhibition have been observed in actively treated patients. By selectively targeting JAK1, such adverse events could be expected to be avoided. This open label study was designed to enrol 15 patients with UC, however the trial was discontinued after two inclusions due to safety concerns with the agent in a parallel trial for systemic lupus erythematosus...
August 7, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28780423/cinnamic-acid-derivatives-inhibit-hepatitis-c-virus-replication-via-the-induction-of-oxidative-stress
#2
Ryota Amano, Atsuya Yamashita, Hirotake Kasai, Tomoka Hori, Sayoko Miyasato, Setsu Saito, Hiromasa Yokoe, Kazunori Takahashi, Tomohisa Tanaka, Teruhime Otoguro, Shinya Maekawa, Nobuyuki Enomoto, Masayoshi Tsubuki, Kohji Moriishi
Several cinnamic acid derivatives have been reported to exhibit antiviral activity. In this study, we prepared 17 synthetic cinnamic acid derivatives and screened them to identify an effective antiviral compound against hepatitis C virus (HCV). Compound 6, one of two hit compounds, suppressed the viral replications of genotypes 1b, 2a, 3a, and 4a with EC50 values of 1.5-8.1 μM and SI values of 16.2-94.2. The effect of compound 6 on the phosphorylation of Tyr(705) in signal transducer and activator of transcription 3 (STAT3) was investigated because a cinnamic acid derivative AG490 was reported to suppress HCV replication and the activity of Janus kinase (JAK) 2...
August 2, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28767341/tofacitinib-as-induction-and-maintenance-therapy-for-ulcerative-colitis
#3
LETTER
(no author information available yet)
New England Journal of Medicine, Volume 377, Issue 5, Page 496-497, August 2017.
August 3, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28765121/novel-therapies-for-immune-mediated-inflammatory-diseases-what-can-we-learn-from-their-use-in-rheumatoid-arthritis-spondyloarthritis-systemic-lupus-erythematosus-psoriasis-crohn-s-disease-and-ulcerative-colitis
#4
REVIEW
Kenneth F Baker, John D Isaacs
The past three decades have witnessed remarkable advances in our ability to target specific elements of the immune and inflammatory response, fuelled by advances in both biotechnology and disease knowledge. As well as providing superior treatments for immune-mediated inflammatory diseases (IMIDs), such therapies also offer unrivalled opportunities to study the underlying immunopathological basis of these conditions.In this review, we explore recent approaches to the treatment of IMIDs and the insights to pathobiology that they provide...
August 1, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28757262/tofacitinib-is-the-right-octave-for-ulcerative-colitis
#5
Lieven Pouillon, Peter Bossuyt, Laurent Peyrin-Biroulet
No abstract text is available yet for this article.
July 27, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28755063/brazilian-experience-of-the-treatment-of-alopecia-universalis-with-the-novel-antirheumatic-therapy-tofacitinib-a-case-series
#6
Morton Scheinberg, Regina Adalva de Lucena Couto Océa, Boris Afonso Cruz, Sineida Berbert Ferreira
INTRODUCTION: Alopecia universalis is an autoimmune disorder for which there is no known effective therapy. Tofacitinib-a novel antirheumatic therapy for rheumatoid arthritis-has been shown in some reports to induce sustained hair growth in patients with alopecia universalis. CASE SERIES: Here, we review the experiences of four different rheumatologists across the country regarding four Brazilian patients with alopecia universalis who were treated with tofacitinib ...
July 28, 2017: Rheumatology and Therapy
https://www.readbyqxmd.com/read/28754958/a-study-on-the-risk-of-fungal-infection-with-tofacitinib-cp-690550-a-novel-oral-agent-for-rheumatoid-arthritis
#7
Yong Chen, Fang-Yuan Gong, Zhen-Jun Li, Zheng Gong, Zhe Zhou, Shu-Yan Ma, Xiao-Ming Gao
Tofacitinib (CP-690550), an oral Janus kinase inhibitor, has shown significant efficacy in the treatment of rheumatoid arthritis through blocking the signaling pathways of pro-inflammatory cytokines. However, recent evidence suggests that long-term tofacitinib treatment is associated with increased risk of infection (e.g. tuberculosis) in patients. In the present study, we illustrate that tofacitinib administration significantly reduced the survival rate of mice given lethal or sub-lethal dose challenge with Candida albicans...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28752178/inhibitory-effect-of-jak-inhibitor-on-mechanical-stress-induced-protease-expression-by-human-articular-chondrocytes
#8
Takahiro Machida, Keiichiro Nishida, Yoshihisa Nasu, Ryuichi Nakahara, Masatsugu Ozawa, Ryozo Harada, Masahiro Horita, Ayumu Takeshita, Daisuke Kaneda, Aki Yoshida, Toshifumi Ozaki
OBJECTIVE: To investigate whether janus kinase (JAK) inhibitor exhibits a chondro-protective effect against mechanical stress-induced expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) and matrix metalloproteinase (MMPs) in human chondrocytes. MATERIALS AND METHODS: Normal human articular chondrocytes were seeded onto stretch chambers and incubated with or without tofacitinib (1000 nM) for 12 h before mechanical stimulation or cytokine stimulation...
July 27, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28751001/effect-of-tofacitinib-on-lipid-levels-and-lipid-related-parameters-in-patients-with-moderate-to-severe-psoriasis
#9
Robert Wolk, Ehrin J Armstrong, Peter R Hansen, Bruce Thiers, Shuping Lan, Anna M Tallman, Mandeep Kaur, Svitlana Tatulych
BACKGROUND: Psoriasis is a systemic inflammatory disease associated with increased cardiovascular (CV) risk and altered lipid metabolism. Tofacitinib is an oral Janus kinase inhibitor. OBJECTIVE: The aim of the study was to investigate the effects of tofacitinib on traditional and nontraditional lipid parameters and CV risk markers in patients with psoriasis from a phase III study, OPT Pivotal 1. METHODS: Patients with psoriasis were randomized to tofacitinib 5 or 10 mg twice daily (BID) or placebo BID...
June 24, 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28734661/systematic-literature-review-and-meta-analysis-of-tumor-necrosis-factor-alpha-experienced-rheumatoid-arthritis
#10
Alvin F Wells, Jeffrey R Curtis, Keith A Betts, Kevin Douglas, Ella Xiaoyan Du, Arijit Ganguli
PURPOSE: The goal of this study was to compile all available evidence regarding the efficacy of tumor necrosis factor-α (TNF) inhibitors, non-TNF biologics, and tofacitinib for TNF-experienced patients who have rheumatoid arthritis (RA). METHODS: A systematic literature review of MEDLINE, EMBASE, and rheumatology conference abstracts was performed to identify observational studies and randomized controlled trials (RCTs) reporting American College of Rheumatology response rates (ACR 20/50/70) for adult patients with RA who switched from at least 1 TNF to another TNF or a non-TNF therapy...
July 19, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28730640/2016-updated-thai-rheumatism-association-recommendations-for-the-use-of-biologic-and-targeted-synthetic-disease-modifying-anti-rheumatic-drugs-in-patients-with-rheumatoid-arthritis
#11
Worawit Louthrenoo, Nuntana Kasitanon, Wanruchada Katchamart, Duangkamol Aiewruengsurat, Parawee Chevaisrakul, Praveena Chiowchanwisawakit, Pornchai Dechanuwong, Punchong Hanvivadhanakul, Ajanee Mahakkanukrauh, Siriporn Manavathongchai, Chayawee Muangchan, Pongthorn Narongroeknawin, Veerapong Phumethum, Boonjing Siripaitoon, Anawat Suesuwan, Siraphop Suwannaroj, Parichat Uea-Areewongsa, Sittichai Ukritchon, Paijit Asavatanabodee, Ajchara Koolvisoot, Ratanavadee Nanagara, Kitti Totemchokchyakarn, Kanokrut Nuntirooj, Tasanee Kitumnuaypong
AIM: In June 2015, the Thai Rheumatism Association (TRA) approved an update of its recommendation for the use of biologic disease-modifying anti-rheumatic drugs (bDMARDs) and targeted synthetic (tsDMARD) in the treatment of rheumatoid arthritis (RA) to cover those currently available in Thailand (etanercept, infliximab, golimumab, rituximab, tocilizumab, abatacept and tofacitinib). METHOD: A search of the literature was performed between January 2000 and June 2015...
July 21, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28717940/alopecia-areata-a-comprehensive-review-of-pathogenesis-and-management
#12
REVIEW
Ralph M Trüeb, Maria Fernanda Reis Gavazzoni Dias
Alopecia areata is a common hair loss condition that is characterized by acute onset of non-scarring hair loss in usually sharply defined areas ranging from small patches to extensive or less frequently diffuse involvement. Depending on its acuity and extent, hair loss is an important cause of anxiety and disability. The current understanding is that the condition represents an organ-specific autoimmune disease of the hair follicle with a genetic background. Genome-wide association studies provide evidence for the involvement of both innate and acquired immunity in the pathogenesis, and mechanistic studies in mouse models of alopecia areata have specifically implicated an IFN-γ-driven immune response, including IFNγ, IFNγ-induced chemokines and cytotoxic CD8 T cells as the main drivers of disease pathogenesis...
July 17, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28714180/tofacitinib-for-the-treatment-of-moderate-to-severe-chronic-plaque-psoriasis-in-japanese-patients-subgroup-analyses-from-a-randomized-placebo-controlled-phase-3-trial
#13
Masatoshi Abe, Chikako Nishigori, Hideshi Torii, Hironobu Ihn, Kei Ito, Makoto Nagaoka, Naoki Isogawa, Isao Kawaguchi, Yukiko Tomochika, Mihoko Kobayashi, Anna M Tallman, Kim A Papp
Tofacitinib is an oral Janus kinase inhibitor. These post-hoc analyses assessed tofacitinib efficacy and safety in Japanese patients with psoriasis enrolled in a 52-week global phase 3 study. Patients received tofacitinib 5 mg, tofacitinib 10 mg or placebo twice daily (b.i.d.); placebo-treated patients advanced to tofacitinib at week 16. Primary efficacy end-points were the proportions of patients with 75% or more reduction from baseline Psoriasis Area and Severity Index (PASI-75) and Physician's Global Assessment (PGA) of "clear" or "almost clear" (PGA response) at week 16...
July 17, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/28711084/herpes-zoster-in-psoriasis-patients-treated-with-tofacitinib
#14
Kevin L Winthrop, Mark Lebwohl, Arnon D Cohen, Jeffrey M Weinberg, Stephen K Tyring, Scott T Rottinghaus, Pankaj Gupta, Kaori Ito, Huaming Tan, Mandeep Kaur, Alexander Egeberg, Lotus Mallbris, Hernan Valdez
BACKGROUND: Tofacitinib is an oral Janus kinase (JAK) inhibitor. Immunomodulatory therapies can increase the risk for herpes zoster (HZ) in patients with psoriasis. OBJECTIVE: To evaluate the relationship between tofacitinib use and HZ risk. METHODS: We used phases 2 and 3 and long-term extension (LTE) data from the tofacitinib development program in psoriasis to calculate HZ incidence rates (IR; events per 100 patient-years); potential HZ risk factors were evaluated using Cox-proportional hazard models...
August 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28681115/-psoriatic-arthritis-drugs-of-the-near-future
#15
REVIEW
D Redelstein, M Fleck
The treatment of psoriatic arthritis (PsA) necessitates different and highly effective treatment strategies due to the diverse clinical manifestations. Drugs that exhibit efficacy for most of the musculoskeletal (e.g. arthritis, dactylitis, enthesitis and spondyloarthritis) and extra-articular manifestations (e.g. skin and nail lesions) are therefore of special interest. This review presents a selection of drugs for the treatment of PsA, which might be available within the (near) future. Based on an improved understanding of the pathopysiology of psoriasis as well as PsA, novel therapeutic approaches are under development...
July 5, 2017: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/28674959/treatment-persistence-and-clinical-outcomes-of-tumor-necrosis-factor-inhibitor-cycling-or-switching-to-a-new-mechanism-of-action-therapy-real-world-observational-study-of-rheumatoid-arthritis-patients-in-the-united-states-with-prior-tumor-necrosis-factor-inhibitor
#16
Wenhui Wei, Keith Knapp, Li Wang, Chieh-I Chen, Gary L Craig, Karen Ferguson, Sergio Schwartzman
INTRODUCTION: To examine treatment persistence and clinical outcomes associated with switching from a tumor necrosis factor inhibitor (TNFi) to a medication with a new mechanism of action (MOA) (abatacept, anakinra, rituximab, tocilizumab, or tofacitinib) versus cycling to another TNFi (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab) among patients with rheumatoid arthritis. METHODS: This retrospective, longitudinal study included patients with rheumatoid arthritis in the JointMan(®) US clinical database who received a TNFi in April 2010 or later and either cycled to a TNFi or switched to a new MOA therapy by March 2015...
July 3, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28654918/serum-human-beta-defensin-2-is-a-possible-biomarker-for-monitoring-response-to-jak-inhibitor-in-psoriasis-patients
#17
Tingting Jin, Ziwen Sun, Xixue Chen, Yun Wang, Ruoyu Li, Suzhen Ji, Yi Zhao
AIMS: To analyse the correlation between serum human beta-defensin-2 (hBD-2) levels and response to JAK inhibitor in psoriasis. METHODS: We evaluated the psoriasis area and severity index (PASI) and serum hBD-2 levels of 18 psoriasis patients randomized to receive placebo or tofacitinib 5 or 10 mg b.i.d. at baseline, week 8, and week 16. Serum hBD-2 levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The PASI achieved a dramatic reduction after tofacitinib 5 or 10 mg b...
June 28, 2017: Dermatology: International Journal for Clinical and Investigative Dermatology
https://www.readbyqxmd.com/read/28646516/tofacitinib-restores-the-inhibition-of-reverse-cholesterol-transport-induced-by-inflammation-understanding-the-lipid-paradox-associated-with-rheumatoid-arthritis
#18
S Pérez-Baos, J I Barrasa, P Gratal, A Larrañaga-Vera, I Prieto-Potin, G Herrero-Beaumont, R Largo
BACKGROUND AND PURPOSE: Patients with active rheumatoid arthritis (RA) have increased cardiovascular mortality, paradoxically associated with reduced circulating lipid levels. The JAK inhibitor tofacitinib ameliorates systemic and joint inflammation in RA with a concomitant increase in serum lipids. We analysed the effect of tofacitinib on the lipid profile of hyperlipidaemic rabbits with chronic arthritis (CA) and on the changes in reverse cholesterol transport (RCT) during chronic inflammation...
June 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28635319/a-case-of-topical-ruxolitinib-treatment-failure-in-alopecia-areata
#19
Maya Deeb, Renée A Beach
Alopecia areata (AA) is an autoimmune-mediated, nonscarring form of hair loss. Despite its prevalence, current management options are limited, especially when the disease has progressed to alopecia totalis (AT) or alopecia universalis (AU). Recent evidence that janus kinase (JAK) signaling contributes to AA pathogenesis prompted the investigation of JAK inhibitors such as tofacitinib and ruxolitinib as possible oral treatments. However, the potential for significant adverse effects with systemic JAK inhibition makes local administration a more attractive option...
June 1, 2017: Journal of Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/28633612/clinical-features-and-treatment-outcomes-in-large-granular-lymphocytic-leukemia-lgll
#20
Srinivasa R Sanikommu, Michael J Clemente, Peter Chomczynski, Manuel G Afable, Andres Jerez, Swapna Thota, Bhumika Patel, Cassandra Hirsch, Aziz Nazha, John Desamito, Alan Lichtin, Brad Pohlman, Mikkael A Sekeres, Tomas Radivoyevitch, Jaroslaw P Maciejewski
Large granular lymphocytic leukemia (LGLL) represents a clonal/oligoclonal lymphoproliferation of cytotoxic T and natural killer cells often associated with STAT3 mutations. When symptomatic, due to mostly anemia and neutropenia, therapy choices are often empirically-based, because only few clinical trials and systematic studies have been performed. Incorporating new molecular and flow cytometry parameters, we identified 204 patients fulfilling uniform criteria for LGLL diagnoses and analyzed clinical course with median follow-up of 36 months, including responses to treatments...
June 20, 2017: Leukemia & Lymphoma
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