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https://www.readbyqxmd.com/read/27933673/a-biophysical-and-computational-study-unraveling-the-molecular-interaction-mechanism-of-a-new-janus-kinase-inhibitor-tofacitinib-with-bovine-serum-albumin
#1
Ali Saber Abdelhameed, Saima Nusrat, Mohammad Rehan Ajmal, Syed Mohammad Zakariya, Masihuz Zaman, Rizwan Hasan Khan
The interaction of a recently certified kinase inhibitor Tofacitinib (TFB) with bovine serum albumin (BSA) has been studied, by spectroscopic and molecular docking studies. Spectrofluorimetric measurements at 3 different temperatures (288, 298, and 310 K) showed that TFB quench the intrinsic fluorescence of BSA upon forming a nonfluorescent complex. The intrinsic fluorescence data showed that TFB binds to BSA with binding constant (Kb ) of approximately 10(4) M(-1) , affirming a significant affinity of TFB with BSA...
December 9, 2016: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/27932144/inhibition-of-jak3-and-pkc-via-immunosuppressive-drugs-tofacitinib-and-sotrastaurin-inhibits-proliferation-of-human-b-lymphocytes-in%C3%A2-vitro
#2
M N Martina, M J Ramirez Bajo, E Bañon-Maneus, D Moya Rull, N Hierro-Garcia, I Revuelta, J M Campistol, J Rovira, F Diekmann
BACKGROUND: Antibody-mediated response in solid organ transplantation is critical for graft dysfunction and loss. The use of immunosuppressive agents partially inhibits the B-lymphocyte response leading to a risk of acute and chronic antibody-mediated rejection. This study evaluated the impact of JAK3 and PKC inhibitors tofacitinib (Tofa) and sotrastaurin (STN), respectively, on B-cell proliferation, apoptosis, and activation in vitro. METHODS: Human B cells isolated from peripheral blood of healthy volunteers were cocultured with CD40 ligand-transfected fibroblasts as feeder cells in the presence of interleukin (IL) 2, IL-10, and IL-21...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27931982/jak-inhibitor-tofacitinib-suppresses-interferon-alfa-production-by-plasmacytoid-dendritic-cells-and-inhibits-arthrogenic-and-antiviral-effects-of-interferon-alfa
#3
Patrick P C Boor, Petra E de Ruiter, Patrick S Asmawidjaja, Erik Lubberts, Luc J W van der Laan, Jaap Kwekkeboom
Tofacitinib is an oral Janus kinase inhibitor that is effective for the treatment of rheumatoid arthritis and shows encouraging therapeutic effects in several other autoimmune diseases. A prominent adverse effect of tofacitinib therapy is the increased risk of viral infections. Despite its advanced stage of clinical development, the modes of action that mediate the beneficial and adverse effects of tofacitinib in autoimmune diseases remain unclear. Interferon alfa (IFNα) produced by plasmacytoid dendritic cells (PDCs) is critically involved in the pathogenesis of many systemic autoimmune diseases and in immunity to viral infections...
November 20, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27917098/update-on-tofacitinib-for-inflammatory-bowel-disease
#4
Brian Feagan
No abstract text is available yet for this article.
September 2016: Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27907269/remission-rates-with-tofacitinib-treatment-in-rheumatoid-arthritis-a-comparison-of-various-remission-criteria
#5
Josef S Smolen, Daniel Aletaha, David Gruben, Samuel H Zwillich, Sriram Krishnaswami, Charles Mebus
OBJECTIVE: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Throughout tofacitinib clinical studies, a 28-joint Disease Activity Score (DAS28)-based analysis was used to assess outcomes. In this study, remission rates by various remission criteria were evaluated across five Phase 3 randomized controlled studies. METHODS: Tofacitinib was dosed 5 or 10 mg twice daily (BID), either as monotherapy, or with background methotrexate or other conventional synthetic disease-modifying antirheumatic drugs (DMARDs)...
December 1, 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/27890175/malignancy-and-janus-kinase-inhibition
#6
REVIEW
Padmapriya Sivaraman, Stanley B Cohen
The use of biologics such as anti-tumor necrosis factor and oral Janus kinase inhibitors have revolutionized the treatment of rheumatoid arthritis (RA). The risk of malignancies such as lymphomas, lung cancer, and nonmelanoma skin cancers (NMSCs) is greater in patients with RA compared with the general population. The incidence of all malignancy (excluding NMSC) was similar in tofacitinib users compared with the general population. The rates of overall and site-specific malignancies in patients with RA treated with tofacitinib are similar to what is expected in the RA population and not different from disease-modifying antirheumatic drugs and biologics...
February 2017: Rheumatic Diseases Clinics of North America
https://www.readbyqxmd.com/read/27889300/tofacitinib-versus-biologic-treatments-in-patients-with-active-rheumatoid-arthritis-who-have-had-an-inadequate-response-to-tumor-necrosis-factor-inhibitors-results-from-a-network-meta-analysis
#7
Maria-Cecilia Vieira, Samuel H Zwillich, Jeroen P Jansen, Brielan Smiechowski, Dean Spurden, Gene V Wallenstein
PURPOSE: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This analysis compared the efficacy and safety of tofacitinib with biologic disease-modifying antirheumatic drugs in patients with RA and a prior inadequate response (IR) to tumor necrosis factor inhibitors (TNFi). METHODS: A systematic literature review identified 5 randomized placebo-controlled trials that evaluated tofacitinib or biologic disease-modifying antirheumatic drugs (bDMARDs) against placebo in patient populations with RA with a prior IR to TNFi...
November 23, 2016: Clinical Therapeutics
https://www.readbyqxmd.com/read/27887955/treatment-of-hypereosinophilic-syndrome-with-cutaneous-involvement-with-the-jak-inhibitors-tofacitinib-and-ruxolitinib
#8
Brett King, Alfred Ian Lee, Jaehyuk Choi
No abstract text is available yet for this article.
November 22, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27886691/pharmacotherapy-pearls-for-the-geriatrician-focus-on-oral-disease-modifying-antirheumatic-drugs-including-newer-agents
#9
REVIEW
Ann J Biehl, James D Katz
Providing safe and effective pharmacotherapy to the geriatric patients with rheumatological disorders is an ongoing struggle for the rheumatologist and geriatrician alike. Cohesive communication and partnership can improve the care of these patients and subvert adverse outcomes. Disease-modifying antirheumatic drugs, including methotrexate, hydroxychloroquine, sulfasalazine, and leflunomide, and the newest oral agent for treatment of rheumatoid arthritis, tofacitinib, have distinctive monitoring and adverse effect profiles...
February 2017: Clinics in Geriatric Medicine
https://www.readbyqxmd.com/read/27882833/evaluation-of-real-world-experience-with-tofacitinib-compared-with-adalimumab-etanercept-and-abatacept-in-ra-patients-with-1-previous-biologic-dmard-data-from-a-u-s-administrative-claims-database
#10
James Harnett, Robert Gerber, David Gruben, Andrew S Koenig, Connie Chen
BACKGROUND: Real-world data comparing tofacitinib with biologic disease-modifying antirheumatic drugs (bDMARDs) are limited. OBJECTIVE: To compare characteristics, treatment patterns, and costs of patients with rheumatoid arthritis (RA) receiving tofacitinib versus the most common bDMARDs (adalimumab [ADA], etanercept [ETN], and abatacept [ABA]) following a single bDMARD in a U.S. administrative claims database. METHODS: This study was a retrospective cohort analysis of patients aged ≥ 18 years with an RA diagnosis (ICD-9-CM codes 714...
December 2016: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/27870773/tofacitinib-response-in-juvenile-idiopathic-arthritis-jia-and-collagenous-colitis
#11
Bryon Tseng, Arash Amighi, Kara Bradford, Hanlin L Wang, Terri E Getzug, Ernest Brahn
No abstract text is available yet for this article.
December 2016: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
https://www.readbyqxmd.com/read/27859030/model-informed-development-and-registration-of-a-once-daily-regimen-of-extended-release-tofacitinib
#12
Manisha Lamba, Matthew M Hutmacher, Daniel E Furst, Ara Dikranian, Martin E Dowty, Daniela Conrado, Thomas Stock, Chudy Nduaka, Jack Cook, Sriram Krishnaswami
Extended-release (XR) formulations enable less frequent dosing versus conventional (e.g., immediate release [IR]) formulations. Regulatory registration of such formulations typically requires pharmacokinetic (PK) and clinical efficacy data. Here we illustrate a model-informed, exposure-response (E-R) approach to translate controlled trial data from one formulation to another without a Phase III trial, using a tofacitinib case study. Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA)...
November 17, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27856658/new-targets-in-psoriatic-arthritis
#13
REVIEW
Juergen Braun
PsA is an immune-mediated chronic inflammatory disease that affects both skin and joints; it is a heterogeneous disease characterized by synovitis, enthesitis, dactylitis and spondylitis. The impact on patients and the burden of disease are substantial. For assessment of the disease, patient-reported outcomes are increasingly important. Conventional therapy consists of NSAIDs, local and systemic CSs, and synthetic and biological DMARDs. While MTX, LEF, SSZ and CYC are the synthetic drugs mainly used, TNF-α blocking agents have represented the majority of biologics used in the last decade (infliximab, etanercept, adalimumab, certolizumab and golimumab)...
December 2016: Rheumatology
https://www.readbyqxmd.com/read/27855242/biologic-or-tofacitinib-monotherapy-for-rheumatoid-arthritis-in-people-with-traditional-disease-modifying-anti-rheumatic-drug-dmard-failure-a-cochrane-systematic-review-and-network-meta-analysis-nma
#14
REVIEW
Jasvinder A Singh, Alomgir Hossain, Elizabeth Tanjong Ghogomu, Amy S Mudano, Peter Tugwell, George A Wells
BACKGROUND: We performed a systematic review, a standard meta-analysis and network meta-analysis (NMA), which updates the 2009 Cochrane Overview, 'Biologics for rheumatoid arthritis (RA)'. This review is focused on biologic monotherapy in people with RA in whom treatment with traditional disease-modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX) had failed (MTX/other DMARD-experienced). OBJECTIVES: To assess the benefits and harms of biologic monotherapy (includes anti-tumor necrosis factor (TNF) (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab) or non-TNF (abatacept, anakinra, rituximab, tocilizumab)) or tofacitinib monotherapy (oral small molecule) versus comparator (placebo or MTX/other DMARDs) in adults with RA who were MTX/other DMARD-experienced...
November 17, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27836567/management-of-psoriatic-arthritis-early-diagnosis-monitoring-of-disease-severity-and-cutting-edge-therapies
#15
REVIEW
Siba P Raychaudhuri, Reason Wilken, Andrea C Sukhov, Smriti K Raychaudhuri, Emanual Maverakis
Psoriatic arthritis (PsA) is a heterogeneous disease that can involve a variety of distinct anatomical sites including a patient's peripheral and axial joints, entheses, skin and nails. Appropriate management of PsA requires early diagnosis, monitoring of disease activity, and utilization of cutting edge therapies. To accomplish the former there are a variety of PsA-specific tools available to screen, diagnose, and assess patients. This review will outline the recently developed PsA screening tools, including the Toronto Psoriatic Arthritis Screening Questionnaire (TOPAS), the Psoriasis Epidemiology Screening Tool (PEST), the Psoriatic Arthritis Screening and Evaluation (PASE), and the Psoriasis and Arthritis Screening Questionnaire (PASQ)...
November 8, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27832357/emerging-biologics-in-inflammatory-bowel-disease
#16
REVIEW
Heyson Chi-Hey Chan, Siew Chien Ng
Early biologic therapy is recommended in patients with inflammatory bowel disease and poor prognostic factors and in those refractory to conventional medications. Anti-tumor necrosis factor (anti-TNF) agents are the most commonly used biologic agents. However, some patients may not have an initial response to anti-TNF therapy, and one-third will develop loss of response over time. Anti-TNF drugs can also be associated with side effects. In addition, the use of biologics is currently limited by their cost, especially in developing countries...
November 10, 2016: Journal of Gastroenterology
https://www.readbyqxmd.com/read/27820799/profiling-drugs-for-rheumatoid-arthritis-that-inhibit-synovial-fibroblast-activation
#17
Douglas S Jones, Anne P Jenney, Jennifer L Swantek, John M Burke, Douglas A Lauffenburger, Peter K Sorger
Activation of synovial fibroblasts (SFs) contributes to rheumatoid arthritis (RA) by damaging synovial membranes and generating inflammatory cytokines that recruit immune cells to the joint. In this paper we profile cytokine secretion by primary human SFs from healthy tissues and from donors with RA and show that SF activation by TNF, IL-1α, and polyinosinic-polycytidylic acid (Poly(I:C)) cause secretion of multiple cytokines found at high levels in RA synovial fluids. We used interaction multiple linear regression to quantify therapeutic and countertherapeutic drug effects across activators and donors and found that the ability of drugs to block SF activation was strongly dependent on the identity of the activating cytokine...
October 31, 2016: Nature Chemical Biology
https://www.readbyqxmd.com/read/27816293/tofacitinib-for-the-treatment-of-severe-alopecia-areata-and-variants-a-study-of-90-patients
#18
Lucy Y Liu, Brittany G Craiglow, Feng Dai, Brett A King
BACKGROUND: Alopecia areata (AA) is a common autoimmune disorder. There are no reliably effective therapies for AA. OBJECTIVE: We sought to evaluate the safety and efficacy of the Janus kinase 1/3 inhibitor, tofacitinib, in a series of patients over an extended period of time. METHODS: This is a retrospective study of patients age 18 years or older with AA with at least 40% scalp hair loss treated with tofacitinib. The primary end point was the percent change in Severity of Alopecia Tool (SALT) score during treatment...
November 2, 2016: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/27816292/tofacitinib-for-the-treatment-of-alopecia-areata-and-variants-in-adolescents
#19
Brittany G Craiglow, Lucy Y Liu, Brett A King
BACKGROUND: There are no reliably effective therapies for alopecia areata (AA). OBJECTIVE: We sought to evaluate the benefit and adverse effects of the Janus kinase 1/3 inhibitor, tofacitinib, in a series of adolescent patients with AA. METHODS: We reviewed the records of 13 adolescent patients with AA treated with tofacitinib. Severity of disease was assessed using the Severity of Alopecia Tool (SALT). Adverse events were evaluated by laboratory monitoring, physical examinations, and review of systems...
November 2, 2016: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/27795451/3-deoxysappanchalcone-promotes-proliferation-of-human-hair-follicle-dermal-papilla-cells-and-hair-growth-in-c57bl-6-mice-by-modulating-wnt-%C3%AE-catenin-and-stat-signaling
#20
Young Eun Kim, Hyung Chul Choi, In-Chul Lee, Dong Yeon Yuk, Hyosung Lee, Bu Young Choi
3-Deoxysappanchalcone (3-DSC) has been reported to possess anti-allergic, antiviral, anti-inflammatory and antioxidant activities. In the present study, we investigated the effects of 3-DSC on the proliferation of human hair follicle dermal papilla cells (HDPCs) and mouse hair growth in vivo. A real-time cell analyzer system, luciferase assay, Western blot and real-time polymerase chain reaction (PCR) were employed to measure the biochemical changes occurring in HDPCs in response to 3-DSC treatment. The effect of 3-DSC on hair growth in C57BL/6 mice was also examined...
November 1, 2016: Biomolecules & Therapeutics
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