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Leflunomide

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https://www.readbyqxmd.com/read/29427785/mitochondrial-dysfunction-induced-by-leflunomide-and-its-active-metabolite
#1
Jiekun Xuan, Zhen Ren, Tao Qing, Letha Couch, Leming Shi, William H Tolleson, Lei Guo
Leflunomide, an anti-inflammatory drug used for the treatment of rheumatoid arthritis, has been marked with a black box warning regarding an increased risk of liver injury. The active metabolite of leflunomide, A771726, which also carries a boxed warning about potential hepatotoxicity, has been marketed as teriflunomide for the treatment of relapsing multiple sclerosis. Thus far, however, the mechanism of liver injury associated with the two drugs has remained elusive. In this study, cytotoxicity assays showed that ATP depletion and subsequent LDH release were induced in a time- and concentration-dependent manner by leflunomide in HepG2 cells, and to a lesser extent, by A77 1726...
February 7, 2018: Toxicology
https://www.readbyqxmd.com/read/29423085/the-anti-rheumatic-drug-leflunomide-synergizes-with-mek-inhibition-to-suppress-melanoma-growth
#2
Kimberley Hanson, Stephen R Robinson, Karamallah Al-Yousuf, Adam E Hendry, Darren W Sexton, Victoria Sherwood, Grant N Wheeler
Cutaneous melanoma, which develops from the pigment producing cells called melanocytes, is the most deadly form of skin cancer. Unlike the majority of other cancers, the incidence rates of melanoma are still on the rise and the treatment options currently available are being hindered by resistance, limited response rates and adverse toxicity. We have previously shown that an FDA approved drug leflunomide, used for rheumatoid arthritis (RA), also holds potential therapeutic value in treating melanoma especially if used in combination with the mutant BRAF inhibitor, vemurafenib...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29367676/inhibition-of-angiogenesis-by-leflunomide-via-targeting-the-soluble-ephrin-a1-epha2-system-in-bladder-cancer
#3
Maolin Chu, Chunying Zhang
Angiogenesis plays an important role in bladder cancer (BCa). The immunosuppressive drug leflunomide has attracted worldwide attention. However, the effects of leflunomide on angiogenesis in cancer remain unclear. Here, we report the increased expression of soluble ephrin-A1 (sEphrin-A1) in supernatants of BCa cell lines (RT4, T24, and TCCSUP) co-cultured with human umbilical vein endothelial cells (HUVECs) compared with that in immortalized uroepithelial cells (SV-HUC-1) co-cultured with HUVECs. sEphrin-A1 is released from BCa cells as a monomeric protein that is a functional form of the ligand...
January 24, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29357281/leflunomide-a-promising-drug-with-good-antitumor-potential
#4
Chunying Zhang, Maolin Chu
Leflunomide, an inhibitor of dihydroorotase dehydrogenase and thereby pyrimidine synthesis, was approved for treatment of rheumatoid arthritis in 1998. During the following years, leflunomide was used in various preclinical studies as a potential cancer treatment; at the same time, more mechanisms underlying the anticancer effect of leflunomide were identified. Thus, leflunomide has been identified as a potent anticancer drug. This article summarizes the mechanisms as well as results of leflunomide in the evolving field of cancer therapy...
January 18, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29348830/inactivation-deficiency-of-dhodh-induces-cell-cycle-arrest-and-programed-cell-death-in-melanoma
#5
Lichao Liu, Zhen Dong, Qian Lei, Jie Yang, Huanrong Hu, Qian Li, Yacong Ji, Leiyang Guo, Yanli Zhang, Yaling Liu, Hongjuan Cui
Malignant melanoma (MM) is one of the most malignant tumors and has a very poor prognosis. However, there are no effective drugs to treat this disease. As a kind of iron flavin dependent enzyme, dihydroorotate dehydrogenase (DHODH, EC 1.3.3.1) is the fourth and a key enzyme in the de novo biosynthesis of pyrimidines. Herein, we found that DHODH inactivation/deficiency inhibited melanoma cell proliferation, induced cell cycle arrest at S phase and lead to autophagy in human melanoma cells. Meanwhile, leflunomide treatment induced cell apoptosis and deficiency of DHODH sensitized cells to drug-induced apoptosis in BCL-2 deficient melanoma cells, while not in BCL-2 abundant melanoma cells...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29330273/rheumatoid-disease-an-unusual-cause-of-relapsing-meningoencephalitis
#6
Sian K Alexander, Maria Di Cicco, Ute Pohl, Alberto Cifelli
A 73-year-old man presented with three episodes of dysphasia and disinhibited behaviour, a single seizure and transient ischaemic attack-like events characterised by right arm and/or leg weakness. These episodes were separated by month-long asymptomatic intervals. Medical history included rheumatoid arthritis, which was clinically quiescent on leflunomide.Repeated cerebrospinal fluid examination showed a persistent lymphocytosis with mildly reduced glucose and elevated protein; oligoclonal bands and viral PCR were negative...
January 12, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29329993/pulmonary-arterial-hypertension-in-four-patients-treated-by-leflunomide
#7
Valentin Coirier, Alain Lescoat, Céline Chabanne, Maxime Fournet, Guillaume Coiffier, Stéphane Jouneau, Elisabeth Polard, Patrick Jégo
Pulmonary arterial hypertension (PAH) is a rare disorder that can be drug-induced, mostly following treatment by appetite-suppressant drugs. We report four cases of patients who developed PAH following a treatment by leflunomide for rheumatoid arthritis, psoriatic arthritis or undetermined connective tissue disease. All patients described a progressive dyspnea from grade II to IV of NYHA classification; clinical examination found signs of heart failure. PAH was finally diagnosed and confirmed by right heart catheterisation...
January 9, 2018: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/29329602/abatacept-used-in-combination-with-non-methotrexate-disease-modifying-antirheumatic-drugs-a-descriptive-analysis-of-data-from-interventional-trials-and-the-real-world-setting
#8
Rieke Alten, Harald Burkhardt, Eugen Feist, Klaus Krüger, Juergen Rech, Andrea Rubbert-Roth, Reinhard E Voll, Yedid Elbez, Christiane Rauch
BACKGROUND: Methotrexate (MTX) remains the anchor drug in rheumatoid arthritis (RA) treatment, but is poorly tolerated or contraindicated in some patients. There is a wealth of data supporting the use of abatacept in combination with MTX, but data on alternative conventional synthetic disease-modifying antirheumatic drug (csDMARD) combinations with abatacept are scarce. METHODS: In this post-hoc exploratory analysis, efficacy and safety data were extracted from abatacept RA studies in which combination with csDMARDs other than MTX was permitted: three interventional trials (ATTAIN, ASSURE, and ARRIVE) and one real-world study (ACTION)...
January 2, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29315647/antiviral-activity-of-a771726-the-active-metabolite-of-leflunomide-against-jun%C3%A3-n-virus
#9
Claudia S Sepúlveda, Cybele C García, Elsa B Damonte
The aim of this study was to investigate the effect of A771726, the active metabolite of leflunomide, against the infection with Junín virus (JUNV), agent of Argentine hemorrhagic fever (AHF). The treatment with non-cytotoxic concentrations of A771726 of Vero and A549 cells infected with JUNV inhibited virus replication in a dose-dependent manner, as determined by virus yield reduction assay. The antiviral effectiveness of A771726 was not importantly affected by the multiplicity of infection and the virus strain...
January 5, 2018: Journal of Medical Virology
https://www.readbyqxmd.com/read/29313271/mri-assessment-of-erosion-repair-in-patients-with-long-standing-rheumatoid-arthritis-receiving-double-filtration-plasmapheresis-in-addition-to-leflunomide-and-methotrexate-a-randomized-controlled-trial
#10
Xiaoxia Yu, Lei Zhang, Lixin Wang, Weiwei Lu, Fengyan Sun, Ping Xu, Guobin Lan
The objective of this study is to investigate whether the addition of double-filtration plasmapheresis (DFPP) to leflunomide and methotrexate repairs MRI bone erosion in patients with long-standing rheumatoid arthritis (RA). Seventy-two patients with highly active RA of > 3 years' duration were randomized to receive DFPP in addition to DMARDs (leflunomide and methotrexate) or DMARDs. Contrast-enhanced MRI of the right wrist was performed at months 0, 6, and 12. MRI bone erosion, synovitis, and bone edema were scored with validated methods...
January 8, 2018: Clinical Rheumatology
https://www.readbyqxmd.com/read/29283072/onset-of-hypertension-in-leflunamide-treated-low-socioeconomic-rheumatoid-arthritis-patients-an-unseen-iceberg
#11
Muhammad Ishaq, Salma Razzaque, Fadieleh Shohail, Ajeet Kumar, Jibran Sualeh Muhammad
OBJECTIVE: To determine the frequency of new-onset hypertension in patients with Rheumatoid arthritis taking leflunomide, in comparison with methotrexate in Asian setting. MATERIAL AND METHODS: Perspective case-control study was conducted in 2014 in a tertiary care hospital located in Karachi Pakistan. Adult patients having rheumatoid arthritis were randomly prescribed leflunomide or methotrexate. Patients having chronic hypertension, proteinuria and chronic kidney disease were excluded...
December 27, 2017: Current Rheumatology Reviews
https://www.readbyqxmd.com/read/29248714/foxq1-ndrg1-axis-exacerbates-hepatocellular-carcinoma-initiation-via-enhancing-crosstalk-between-fibroblasts-and-tumor-cells
#12
Qin Luo, Chao-Qun Wang, Lu-Yu Yang, Xiao-Mei Gao, Hao-Ting Sun, Yu Zhang, Kai-Li Zhang, Ying Zhu, Yan Zheng, Yuan-Yuan Sheng, Lu Lu, Hu-Liang Jia, Wen-Qiang Yu, Jie Liu, Qiong-Zhu Dong, Lun-Xiu Qin
Cancer associated fibroblast (CAF) is a well-known microenvironment contributor for the development of hepatocellular carcinoma (HCC), while forkhead box (FOX) proteins are also critical to exacerbate HCC malignancy. However, whether FOX proteins are involved in the crosstalk between CAFs and HCC cells remains unclear. In the present study, we reveal that CAFs induce forkhead box Q1 (FOXQ1) expression, and N-myc downstream-regulated gene 1 (NDRG1) is therefore trans-activated to enhance HCC initiation. Intriguingly, pSTAT6/C-C motif chemokine ligand 26 (CCL26) signaling is induced by FOXQ1/NDRG1 axis, thus recruiting hepatic stellate cells (HSCs), the main cellular source of CAFs, to the tumor microenvironment...
December 15, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29231235/the-perioperative-use-of-synthetic-and-biological-disease-modifying-antirheumatic-drugs-in-patients-with-rheumatoid-arthritis
#13
Gregory Fleury, Sylvano Mania, Didier Hannouche, Cem Gabay
Disease-modifying antirheumatic drugs (DMARDs) have become essential treatments in the management of patients with inflammatory rheumatic diseases. Their use has resulted in a marked improvement of disease control and a limitation of joint damage, although some patients still require subsequent corrective or joint replacement surgery. Due to their immunosuppressive effects, some DMARDs are associated with an increased risk of infection. The aim of this review is to discuss the available literature on the management of DMARDs during the perioperative period, particularly in the case of orthopaedic surgery...
December 12, 2017: Swiss Medical Weekly
https://www.readbyqxmd.com/read/29226391/experience-with-leflunomide-as-treatment-and-as-secondary-prophylaxis-for-cytomegalovirus-infection-in-lung-transplant-recipients-a-case-series-and-review-of-the-literature
#14
Jose Tiago Silva, Virginia Pérez-González, Francisco López-Medrano, Rodrigo Alonso-Moralejo, Mario Fernández-Ruiz, Rafael San-Juan, Patricia Brañas, María Dolores Folgueira, José María Aguado, Alicia de Pablo-Gafas
Data concerning the use of leflunomide -a drug approved for rheumatoid arthritis with in vitro anti-cytomegalovirus (CMV) activity- in lung transplant (LT) recipients are scarce. We performed a single center retrospective study including LT recipients who received leflunomide for CMV infection or as secondary prophylaxis after viremia clearance. We also conducted a full systematic PubMed search until June 30, 2017. We identified 5 LT recipients in our center, plus 7 patients reported in the literature. All patients had previously received ganciclovir (GCV) and foscarnet, with drug-induced adverse effects described in 6 recipients (50%)...
December 11, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/29222360/antiviral-treatment-of-bk-virus-viremia-after-kidney-transplantation
#15
REVIEW
Andrew D Santeusanio, Benjamin E Lukens, Judy Eun
PURPOSE: The various antiviral treatment options in the management of BK virus (BKV) viremia and BKV-associated nephropathy (BKVAN) are reviewed. SUMMARY: Review of the PubMed database from 1990 to 2016 for all English language case series, cohort studies, and randomized controlled trials detailing antiviral treatment of BKV viremia or BKVAN in kidney transplant recipients returned only 16 published reports. The majority of these reports were based on small case series or protocol-based cohort studies, with no prospective head-to-head data and only modest benefit reported for cidofovir, leflunomide, i...
December 15, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/29222350/leflunomide-use-during-pregnancy-and-the-risk-of-adverse-pregnancy-outcomes
#16
Anick Bérard, Jin-Ping Zhao, Irene Shui, Susan Colilla
OBJECTIVES: Leflunomide is known to be embryotoxic and teratogenic in rodents. However, there is less evidence in humans. We quantified the risk of major congenital malformation (MCM), prematurity, low birth weight (LBW) and spontaneous abortion associated with leflunomide exposure during pregnancy in humans. METHODS: From a cohort of 289 688 pregnancies in Montreal, Quebec, Canada, from 1998 to 2015, first-trimester leflunomide exposure and other antirheumatic drug exposures were studied for their association with MCM and spontaneous abortions...
December 8, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29192568/-polymyalgia-rheumatica-new-developments-and-challenges
#17
D E Marsman, A A den Broeder, N Boers, A van der Maas
- Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disorder in which inflammation markers, both erythrocyte sedimentation rate (ESR) and CRP values, are often elevated. However, a non-abnormal ESR or CRP value does not preclude the diagnosis.- PMR is an arbitrary diagnosis and presents both diagnostic and therapeutic challenges.- Imaging diagnostics, such as echography, MRI or FDG-PET/CT, may potentially be applied more frequently as a second-line investigation when there is doubt concerning the diagnosis...
2017: Nederlands Tijdschrift Voor Geneeskunde
https://www.readbyqxmd.com/read/29141925/unusual-salmonella-typhi-periprosthetic-joint-infection-involving-bilateral-knees-management-options-and-literature-review
#18
Ashok Rajgopal, Inayat Panda, Anu Gupta
A 70-year-old Indian woman, who had undergone primary bilateral total knee arthroplasty (TKA) for rheumatoid arthritis 10 months prior, presented with 10 days history of pain, swelling and erythema over both knees with pus discharging from the right knee. She had type 2 diabetes mellitus and was on long-term steroid, leflunomide and antitumour necrosis factor therapy for rheumatoid arthritis. Her clinical and laboratory features were suggestive of a haematogenous periprosthetic joint infection (PJI). The final diagnosis of bilateral Salmonella typhi PJI was made based on culture reports...
November 14, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/29134512/artery-compliance-in-patients-with-rheumatoid-arthritis-results-from-a-case-control-study
#19
Lei Wang, Wenfeng Tan, Fang Wang, Youxuan Shen, Huanping Mei, Yanyan Wang, Yao Ke, Lei Gu, Qiang Wang, Miaojia Zhang
Atherosclerosis is one of the most common complications of rheumatoid arthritis (RA). The objective of this study is to evaluate differences in large artery compliance (C1) and small artery compliance (C2) between RA and controls and evaluating factors associated with reduced compliance in the RA population. The profiling of large and small arterial compliance was analyzed in 185 RA patients and 88 healthy controls using Cardiovascular Profiling Instrument. The correlations of arterial compliance and the relevant clinical data were determined in these subjects...
November 13, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/29116543/remission-assessment-of-rheumatoid-arthritis-in-daily-practice-in-china-a-cross-sectional-observational-study
#20
Huaqun Zhu, Ru Li, Zhanyun Da, Liqi Bi, Xiangpei Li, Yang Li, Chongyang Liu, Fengxiao Zhang, Zhijun Li, Xiangyuan Liu, Zhiyi Zhang, Lingyun Sun, Youlian Wang, Wei Zhang, Quan Jiang, Jinwei Chen, Qingping Chen, Zhenbin Li, Lijun Wu, Wencheng Qi, Jianhua Xu, Xiangjun Cui, Xiaofei Wang, Long Li, Xiaomei Leng, Guochun Wang, Dongbao Zhao, Lindi Jiang, Dongyi He, Xiaomin Liu, Ling Li, Yongfei Fang, Cibo Huang, Huaxiang Wu, Shaoxian Hu, Qin Li, Hui Song, Weiguo Xiao, Lu Gong, Liaojia Zhang, Xiaofeng Li, Zhanguo Li, Yin Su
The objective of this study is to evaluate the remission rate and describe the current use of medication in a large cohort of rheumatoid arthritis (RA) patients under routine clinical care in China. RA patients were recruited from 40 large teaching hospitals nationwide in China. Data regarding RA disease activity, medication treatment, and adverse events were recorded using a standardized clinical data questionnaire. RA remission was evaluated by the 28 Joint Disease Activity Score DAS28-ESR Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission criteria...
November 7, 2017: Clinical Rheumatology
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