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https://www.readbyqxmd.com/read/29908669/safety-and-efficacy-of-upadacitinib-in-patients-with-rheumatoid-arthritis-and-inadequate-response-to-conventional-synthetic-disease-modifying-anti-rheumatic-drugs-select-next-a-randomised-double-blind-placebo-controlled-phase-3-trial
#1
Gerd R Burmester, Joel M Kremer, Filip Van den Bosch, Alan Kivitz, Louis Bessette, Yihan Li, Yijie Zhou, Ahmed A Othman, Aileen L Pangan, Heidi S Camp
BACKGROUND: Upadacitinib is a selective inhibitor of Janus kinase 1 and was efficacious in phase 2 studies in patients with moderate-to-severe rheumatoid arthritis. We aimed to assess the efficacy of upadacitinib in patients with inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). METHODS: This study is a double-blind, placebo-controlled trial at 150 sites in 35 countries. We enrolled patients aged 18 years or older with active rheumatoid arthritis for 3 months or longer, who had received csDMARDs for at least 3 months with a stable dose for at least 4 weeks before study entry, and had an inadequate response to at least one of the following csDMARDs: methotrexate, sulfasalazine, or leflunomide...
June 12, 2018: Lancet
https://www.readbyqxmd.com/read/29883224/treatment-of-sarcoidosis-grading-the-evidence
#2
W Ennis James, Robert Baughman
Treatment of sarcoidosis recommendations are often based on clinical experience and expert opinion. However, there are an increasing number of studies which are providing evidence to support decisions regarding treatment. Areas covered: Several studies have identified factors associated with increased risk for organ failure or death ('danger'). There have been several studies focused on the role of treatment to improve quality of life for the patient. Sarcoidosis treatment often follows a progression, based on response...
June 18, 2018: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29871774/high-dose-intravenous-immunoglobulin-treatment-of-polyomavirus-nephropathy-developing-after-t-cell-mediated-rejection-treatment-a-case-report
#3
S D Hwang, J H Lee, S W Lee, J K Kim, M-J Kim, J H Song
BACKGROUND: Reactivation of BK polyomavirus causes destructive virus allograft nephropathy; however, treatment options are limited. Herein, we report a case in which a patient with T cell-mediated rejection was treated with steroid therapy. The patient subsequently developed BK viremia and was successfully treated by using intravenous immunoglobulin (IVIG) after failing to respond to conventional treatment. CASE PRESENTATION: A 54-year-old man had been undergoing peritoneal dialysis for 3 years before kidney transplantation...
June 2, 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29846160/rheumatic-diseases-and-pregnancy-a-national-survey-about-practice-patterns-among-rheumatologists-and-obstetricians
#4
Fouad Fayad, Nelly Ziade, Ghada Abi Karam, Wadih Ghaname, Munther Khamashta
OBJECTIVES: Management of rheumatic diseases (RD) is often problematic in pregnant patients, hence the need for guideline implementation. This survey-based study aimed to assess beliefs among obstetricians and rheumatologists about managing RD in pregnant Lebanese patients. METHODS: Questionnaires were completed by a representative sample of rheumatologists and obstetricians practicing throughout Lebanon. Collected data included physicians' information, opinion on pregnancy in RD patients, compatible drugs with fertility, pregnancy and breastfeeding, references used in their clinical management, referral to specialists, and knowledge about guidelines...
May 24, 2018: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/29802211/leflunomide-counter-akt-s-cardiac-hypertrophy
#5
Luciana A Pescatore, Francisco R M Laurindo
Cardiac hypertrophy (CH) is a major independent risk factor for heart failure and mortality. However, therapeutic interventions that target hypertrophy signaling in a load-independent way are unavailable. In a recent issue of Clinical Science (vol. 132, issue 6, 685-699), Ma et al. describe that the anti-inflammatory drug leflunomide markedly antagonized CH, dysfunction, and fibrosis induced by aortic banding or angiotensin-II in mice or by agonists in cultured cells. Unexpectedly, this occurred not via anti-inflammatory mechanisms but rather via inhibtion of Akt (protein kinase B, PKB) signaling...
May 31, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29786138/association-of-different-immunosuppressive-medications-with-periodontal-condition-in-patients-with-rheumatoid-arthritis-results-from-a-cross-sectional-study
#6
Dirk Ziebolz, Annegret Rupprecht, Jan Schmickler, Laura Bothmann, Juliane Krämer, Daniel Patschan, Gerhard A Müller, Rainer F Mausberg, Jana Schmidt, Gerhard Schmalz, Susann Patschan
BACKGROUND: The aim of this cross-sectional study was to investigate clinical periodontal findings as well as prevalence of selected potentially periodontal pathogenic bacteria in patients with rheumatoid arthritis (RA) treated with different immunosuppressive rheumatic medications. METHODS: 168 patients with RA undergoing different immunosuppressive medications were included and divided into subgroups according to their medication, which was taken in the past six months, in detail I) non-steroidal anti-inflammatory drugs (NSAID) and glucocorticoids combined, and II-VII) different disease modifying anti-rheumatic drugs (DMARDs): II) Methotrexate (MTX), III) Leflunomide, IV) MTX and TNF-α antagonists combined, V) Interleukin-6 (IL-6) antagonist, VI) MTX and Rituximab combined, and VII) combination therapies of more than two of these DMARDs...
May 22, 2018: Journal of Periodontology
https://www.readbyqxmd.com/read/29774784/moderate-alcohol-consumption-is-associated-with-increased-radiological-progression-in-women-but-not-in-men-with-early-rheumatoid-arthritis-results-from-the-espoir-cohort-%C3%A3-tude-et-suivi-des-polyarthrites-indiff%C3%A3-renci%C3%A3-es-r%C3%A3-centes
#7
F Sageloli, J L Quesada, B Fautrel, C Salliot, P Gaudin, A Baillet
OBJECTIVE: We conducted this study to determine whether alcohol consumption influences radiological progression in early rheumatoid arthritis (RA). METHOD: Patients fulfilling the European League Against Rheumatism/American College of Rheumatology 2010 criteria in the early arthritis cohort ESPOIR (Étude et Suivi des Polyarthrites Indifférenciées Récentes) were included in this study. Alcohol consumption was collected at baseline and at each visit. We classified alcohol consumption into three groups: abstinent (0 g/day), moderate (≤ 20 g/day for women, ≤ 30 g/day for men), and abuse (> 20 g/day for women, > 30 g/day for men)...
May 18, 2018: Scandinavian Journal of Rheumatology
https://www.readbyqxmd.com/read/29765444/sequentiality-of-treatment-in-the-rheumatoid-arthritis-drug-programme-in-the-years-2009-2014
#8
Małgorzata Tłustochowicz, Andrzej M Śliwczyński, Melania Brzozowska, Zbigniew Teter, Michał Marczak
Approximately 1% of the population suffers from rheumatoid arthritis (RA) worldwide (0.45% in Poland). The therapy consists of the use of disease-modifying antirheumatic drugs (DMARDs). Biologics are used in the form of the drug programme. Analysis of the NHF database demonstrated the sequence of conversion between drugs and time spent in a single treatment. In 2009, the patients would start the following treatments: adalimumab 5.8%; etanercept 14.4%; infliximab 23.1%; leflunomide 53.6%; rituximab 3%. After the first year 16% of patients changed therapy or abstained, and in the second year this situation affected 65% of patients...
April 2018: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/29749651/effects-of-immunosuppressive-agents-on-the-hemostatic-system-in-normal-dogs
#9
John M Thomason, Todd M Archer, Robert W Wills, Andrew J Mackin
BACKGROUND: In dogs, the effects of immunosuppressive medications on hemostasis are not well known. HYPOTHESIS/OBJECTIVES: The objective was to determine the effects of immunosuppressive medications on primary and secondary hemostasis. Our hypothesis was that cyclosporine and prednisone would increase markers of hypercoagulability and thromboxane synthesis, while azathioprine, mycophenolate mofetil, and leflunomide would have minimal effects on hemostasis. ANIMALS: Eight healthy dogs...
May 10, 2018: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/29664818/initiation-of-disease-modifying-therapies-in-rheumatoid-arthritis-is-associated-with-changes-in-blood-pressure
#10
Joshua F Baker, Brian Sauer, Chia-Chen Teng, Michael George, Grant W Cannon, Said Ibrahim, Amy Cannella, Bryant R England, Kaleb Michaud, Liron Caplan, Lisa A Davis, James OʼDell, Ted R Mikuls
PURPOSE: This study reports the effect of disease-modifying therapies for rheumatoid arthritis (RA) on systolic and diastolic blood pressure (SBP, DBP) over 6 months and incident hypertension over 3 years in a large administrative database. METHODS: We used administrative Veterans Affairs databases to define unique dispensing episodes of methotrexate, leflunomide, sulfasalazine, hydroxychloroquine, tumor necrosis factor inhibitors, and prednisone among patients with RA...
June 2018: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
https://www.readbyqxmd.com/read/29660056/pyomyositis-an-unusual-cause-of-hip-pain-in-a-patient-on-certolizumab-pegol-and-leflunomide
#11
Surabhi Wig, Paul S McCabe, Smrita Swamy, Jawad Sultan, Sreekanth Vasireddy
No abstract text is available yet for this article.
April 6, 2018: Rheumatology
https://www.readbyqxmd.com/read/29644482/metabolic-syndrome-and-the-decreased-levels-of-uric-acid-by-leflunomide-favor-redox-imbalance-in-patients-with-rheumatoid-arthritis
#12
Neide Tomimura Costa, Bruna Miglioranza Scavuzzi, Tatiana Mayumi Veiga Iriyoda, Marcell Alysson Batisti Lozovoy, Daniela Frizon Alfieri, Fabiano Aparecido de Medeiros, Marcelo Cândido de Sá, Pâmela Lonardoni Micheletti, Bruno Alexandre Sekiguchi, Edna Maria Vissoci Reiche, Michael Maes, Andréa Name Colado Simão, Isaias Dichi
Oxidative stress plays a role in the pathophysiology of rheumatoid arthritis (RA). The aim of the present study was to verify the influence of metabolic syndrome (MetS) and disease-modifying antirheumatic drugs on nitrosative and oxidative biomarkers in patients with RA. A total of 177 patients with RA and 150 healthy volunteers participated in this study, which measured lipid hydroperoxides, advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), carbonyl protein, total radical-trapping antioxidant parameter (TRAP), uric acid (UA), and C-reactive protein (CRP)...
April 11, 2018: Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/29618584/leflunomide-increases-hepatic-exposure-to-methotrexate-and-its-metabolite-by-differentially-regulating-multidrug-resistance-associated-protein-mrp2-3-4-transporters-via-peroxisome-proliferator-activated-receptor-%C3%AE-activation
#13
Le Wang, Leilei Ma, Yunfei Lin, Xing Liu, Ling Xiao, Yiting Zhang, Ye Xu, Hu Zhou, Guoyu Pan
Methotrexate (MTX) is the gold standard drug for the treatment of rheumatoid arthritis (RA), and it is frequently combined with leflunomide (LEF) to enhance its clinical efficacy. However, this combination can exacerbate liver toxicity, and the underlying mechanism has not yet been clarified. We investigated whether LEF affects the pharmacokinetics of MTX and its primary toxic metabolite, 7-hydroxyl methotrexate (7OH MTX), in mice. LEF significantly increased the plasma concentration (area under the plasma concentration-time curve) of MTX and 7OH MTX (2...
June 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29608766/life-threatening-reversible-bone-marrow-toxicity-in-a-rheumatoid-arthritis-patient-switched-from-leflunomide-to-infliximab
#14
A Marchesoni, M Arreghini, B Panni, N Battafarano, L Uziel
No abstract text is available yet for this article.
June 1, 2018: Rheumatology
https://www.readbyqxmd.com/read/29547712/flaming-mitochondria-the-anti-inflammatory-drug-leflunomide-boosts-mitofusins
#15
Anna Pellattiero, Luca Scorrano
Despite the significance of mitochondrial dynamics in many diseases, drugs that modulate it are lacking. In this issue of Cell Chemical Biology, Miret-Casals et al. (2018) use a phenotypic high-throughput screen to discover a pro-fusion role for the anti-inflammatory drug Leflunomide, paving the way to screen for mitochondrial pro-fusion drug candidates.
March 15, 2018: Cell Chemical Biology
https://www.readbyqxmd.com/read/29546609/igg4-related-disease-beyond-glucocorticoids
#16
REVIEW
Mitsuhiro Akiyama, Tsutomu Takeuchi
IgG4-related disease is a heterogeneous immune-mediated fibroinflammatory condition that can affect every single organ. This disease is more prevalent in the elderly (the mean age of patients is above 60 years) and the prevalence rate is estimated to be over 4.6 per 100,000 population. Before making a diagnosis, the exclusion of malignancies, lymphoma, anti-neutrophil cytoplasmic antibody-associated vasculitis, multicentric Castleman disease, and other mimickers is crucial for appropriate treatment. Broad management guidelines have been published emphasizing the need for prompt treatment and the use of glucocorticoids as first-line drug therapy for induction of remission...
April 2018: Drugs & Aging
https://www.readbyqxmd.com/read/29540819/inhibition-of-p70-s6-kinase-activity-by-a77-1726-induces-autophagy-and-enhances-the-degradation-of-superoxide-dismutase-1-sod1-protein-aggregates
#17
Jing Sun, Yarong Mu, Yuanyuan Jiang, Ruilong Song, Jianxin Yi, Jingsong Zhou, Jun Sun, Xinan Jiao, Richard A Prinz, Yi Li, Xiulong Xu
Autophagy plays a central role in degrading misfolded proteins such as mutated superoxide dismutase 1 (SOD1), which forms aggregates in motor neurons and is involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). Autophagy is activated when UNC-51-like kinase 1 (ULK1) is phosphorylated at S555 and activated by AMP-activated protein kinase (AMPK). Autophagy is suppressed when ULK1 is phosphorylated at S757 by the mechanistic target of rapamycin (mTOR). Whether p70 S6 kinase 1 (S6K1), a serine/threonine kinase downstream of mTOR, can also regulate autophagy remains uncertain...
March 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29540672/immunosuppressive-effect-of-arsenic-trioxide-on-islet-xenotransplantation-prolongs-xenograft-survival-in-mice
#18
Bin Zhao, Jun-Jie Xia, Lu-Min Wang, Chang Gao, Jia-Li Li, Jia-Yin Liu, Qi-Jun Cheng, Chen Dai, Qi-Lin Ma, Zhong-Quan Qi, Ben-Hua Zhao
The role of arsenic trioxide (As2 O3 ) in inhibiting immune rejection and prolonging islet allograft survival has been identified in islet allotransplantation. This study aims to explore the role of As2 O3 in islet xenotransplantation and the action mechanism. The streptozotocin (STZ) was used in C57BL/6 mice to induce the type 1 diabetes mellitus (T1DM) for xenotransplantation models establishment. Donor islets were isolated by digesting. The flow cytometry (FCM) was used to analyze lymphocyte types. The blood sugar level was detected by using intraperitoneal glucose tolerance test (IPGTT)...
March 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29540538/a77-1726-leflunomide-blocks-and-reverses-cardiac-hypertrophy-and-fibrosis-in-mice
#19
Zhen-Guo Ma, Xin Zhang, Yu-Pei Yuan, Ya-Ge Jin, Ning Li, Chun-Yan Kong, Peng Song, Qi-Zhu Tang
T-cell infiltration and the subsequent increased intracardial chronic inflammation play crucial roles in the development of cardiac hypertrophy and heart failure (HF). A77 1726, the active metabolite of leflunomide, has been reported to have powerful anti-inflammatory and T cell-inhibiting properties. However, the effect of A77 1726 on cardiac hypertrophy remains completely unknown. Herein, we found that A77 1726 treatment attenuated pressure overload or angiotensin II (Ang II)-induced cardiac hypertrophy in vivo , as well as agonist-induced hypertrophic response of cardiomyocytes in vitro In addition, we showed that A77 1726 administration prevented induction of cardiac fibrosis by inhibiting cardiac fibroblast (CF) transformation into myofibroblast...
March 30, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29534752/teriflunomide-promotes-oligodendroglial-differentiation-and-myelination
#20
Peter Göttle, Anastasia Manousi, David Kremer, Laura Reiche, Hans-Peter Hartung, Patrick Küry
BACKGROUND: Multiple sclerosis (MS) is a neuroinflammatory autoimmune disease of the central nervous system (CNS) which in most cases initially presents with episodes of transient functional deficits (relapsing-remitting MS; RRMS) and eventually develops into a secondary progressive form (SPMS). Aside from neuroimmunological activities, MS is also characterized by neurodegenerative and regenerative processes. The latter involve the restoration of myelin sheaths-electrically insulating structures which are the primary targets of autoimmune attacks...
March 13, 2018: Journal of Neuroinflammation
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