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Angelika Drynda, Bożena Obmińska-Mrukowicz, Ewa Zaczyńska, Michał Zimecki, Iwona Kochanowska, Stanisław Ryng, Marcin Mączyński
Isoxazoles are an important class of compounds of potential therapeutic value. The aim of this study was to determine immunotropic effects of 5-amino-3-methyl-4-isoxazolecarboxylic acid hydrazide derivatives on spontaneous and mitogen-induced lymphocyte proliferation in young and old mice, cytokine production by peritoneal cells as well as possible mechanism of action in a model of Jurkat cells. Three month and thirteen month old BALB/c mice were used as donors of the cells from a thymus, a spleen, mesenteric lymph nodes and a peritoneal cavity...
October 25, 2016: Chemical Biology & Drug Design
Nazim Benzerdjeb, Fatima Ameur, Jean-Fortune Ikoli, Henri Sevestre
Primary cardiac B cell lymphoma is rare. To date, fewer than 90 cases have been described in the literature. We report a 67-year-old woman with a 30-year history of rheumatoid arthritis, who had received treatment with leflunomide for 10 years and infliximab for 2 years. Secondary Felty's syndrome appeared. She was admitted to the hospital for abdominal pain. Investigations disclosed a 5cm cardiac mass in the right atrium. Histopathologic examination of tissue specimens obtained at surgical myocardial biopsy demonstrated primary cardiac B cell lymphoma...
October 17, 2016: Pathology, Research and Practice
Sun-Kyeong Park, Seung-Hoo Park, Min-Young Lee, Ji-Hyun Park, Jae-Hong Jeong, Eui-Kyung Lee
PURPOSE: In south Korea, the price of biologics has been decreasing owing to patent expiration and the availability of biosimilars. This study evaluated the cost-effectiveness of a treatment strategy initiated with etanercept (ETN) compared with leflunomide (LFN) after a 30% reduction in the medication cost of ETN in patients with active rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX-IR). METHODS: A cohort-based Markov model was designed to evaluate the lifetime cost-effectiveness of treatment sequence initiated with ETN (A) compared with 2 sequences initiated with LFN: LFN-ETN sequence (B) and LFN sequence (C)...
October 19, 2016: Clinical Therapeutics
Gerd Horneff, Ariane Klein, Prasad T Oommen, Anton Hospach, Ivan Foeldvari, Isa Feddersen, Kirsten Minden
OBJECTIVES: While tumour necrosis factor (TNF)-α-inhibitor treatment improved outcome of juvenile idiopathic arthritis (JIA) management markedly, concerns have been raised about an association of TNF-α-inhibitor treatment and an increased risk for malignancies especially lymphoma. METHODS: Cases of suspected malignancies documented in the German Biker Registry are reviewed in detail. RESULTS: Until Dec 31, 2015, 3695 JIA patients were prospectively followed with a total of more than 13,198 observation years...
September 8, 2016: Clinical and Experimental Rheumatology
Paulina Płoszaj, Andrzej Regiec, Stanisław Ryng, Agnieszka Piwowar, Marian L Kruzel
The 5-amino-3-methyl-4-isoxazolecarboxylic acid hydrazide (HIX) is a synthetic isoxazole derivative with a potential for development as an anti-inflammatory drug candidate. The goal of this study was to explore in vitro autoimmune and inflammatory gene modulation by HIX in human Caco-2 cultured cells. The effect of low dose of HIX was tested on the expression level of RNA in 24h Caco-2 cultures using the QIAGEN Th17 for Autoimmunity & Inflammation RT(2) Profiler PCR Array. We choose the PCR technology as the most reliable and sensitive gene expression profiling method for analyzing specific gene regulatory networks...
October 17, 2016: Immunopharmacology and Immunotoxicology
André Duquette, Anne Julie Frenette, Maxime Doré
OBJECTIVE: To report the case of a patient treated with leflunomide that presented with chronic diarrhea associated with high teriflunomide blood concentration. An 84-year-old woman taking leflunomide 20 mg once daily for the past 2 years to treat rheumatoid arthritis (RA) was investigated for severe chronic diarrhea that had been worsening for the past 5 months. The patient's general condition progressively deteriorated and included electrolyte imbalances and a transient loss of consciousness...
June 2016: Rheumatol Ther
Ashley M Hopkins, Mahin Moghaddami, David Jr Foster, Susanna M Proudman, Richard N Upton, Michael D Wiese
Leflunomide's active metabolite teriflunomide inhibits dihydro-oroate dehydrogenase (DHODH), an enzyme essential to proliferation of T-lymphocytes. As teriflunomide must reach the target site to have this effect, this study assessed the distribution of teriflunomide into T-lymphocytes, as intracellular concentrations may be a superior response biomarker to plasma concentrations. CD3 MicroBeads (MiltenyiBiotec) were used to extract CD3(+) T-cells from the peripheral blood of patients with rheumatoid arthritis whom were taking a stable dose of leflunomide...
October 14, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
A J Ruiz-Padilla, J I Gamez-Nava, A M Saldaña-Cruz, J D Murillo-Vazquez, M L Vazquez-Villegas, S A Zavaleta-Muñiz, B T Martín-Márquez, J M Ponce-Guarneros, N A Rodriguez Jimenez, A Flores-Chavez, F Sandoval-Garcia, J C Vasquez-Jimenez, E G Cardona-Muñoz, S E Totsuka-Sutto, L Gonzalez-Lopez
Objective. To evaluate the association of -174G/C IL-6 polymorphism with failure in therapeutic response to methotrexate (MTX) or leflunomide (LEF). This prospective, observational cohort included 96 Mexican-Mestizo patients with moderate or severe rheumatoid arthritis (RA), initiating MTX or LEF, genotyped for IL-6 -174G/C polymorphism by PCR-RFLP. Therapeutic response was strictly defined: only if patients achieved remission or low disease activity (DAS-28 < 3.2). Results. Patients with MTX or LEF had significant decrement in DAS-28 (p < 0...
2016: BioMed Research International
Andrea Picchianti Diamanti, Milica Markovic, Giuseppe Argento, Simonetta Giovagnoli, Alberto Ricci, Bruno Laganà, Raffaele D'Amelio
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that can present different extrarticular manifestations involving heart, lungs and kidneys. In recent years there has been a growing awareness of the central role played by the lungs in the onset and progression of RA. In particular interstitial lung disease (ILD) is a common pulmonary manifestation that may be related to the inflammatory process itself, infectious complications and to the treatments used. Management of patients with ILD/RA is still a challenge for clinicians, both synthetic [mainly methotrexate (MTX), leflunomide] and biologic immunosuppressors [mainly anti-tumor necrosis factor (TNF)α] have in fact been related to the onset or worsening of lung diseases with conflicting data...
October 12, 2016: Therapeutic Advances in Respiratory Disease
Elisabeth M Hodson, Sophia C Wong, Narelle S Willis, Jonathan C Craig
BACKGROUND: The majority of children who present with their first episode of nephrotic syndrome achieve remission with corticosteroid therapy. Children who fail to respond may be treated with immunosuppressive agents including calcineurin inhibitors (cyclosporin or tacrolimus) and with non-immunosuppressive agents such as angiotensin-converting enzyme inhibitors (ACEi). Optimal combinations of these agents with the least toxicity remain to be determined. This is an update of a review first published in 2004 and updated in 2006 and 2010...
October 11, 2016: Cochrane Database of Systematic Reviews
Bridget Hodkinson, Kingsley Ross Magomero, Mohammed Tikly
BACKGROUND: In resource-constrained settings where biologic agents are not widely available, there are limited therapeutic options for patients with rheumatoid arthritis (RA) refractory to other synthetic disease modifying antirheumatic (DMARD) therapies. The aim of this study is to evaluate the effectiveness and safety of leflunomide (LEF) with methotrexate (MTX) in refractory RA. METHODS: A retrospective record review of adult RA patients treated with LEF/MTX...
October 2016: Therapeutic Advances in Musculoskeletal Disease
Edward Sames, Heather Paterson, Charles Li
Agranulocytosis is a rare and little-known side effect of hydroxychloroquine use. This report describes the case of a 71-year-old woman with poorly controlled rheumatoid arthritis who developed agranulocytosis after several months of hydroxychloroquine therapy. She had been on several different disease-modifying antirheumatic drugs, including methotrexate and leflunomide, for her rheumatoid arthritis. Treatment became complicated following a diagnosis of leflunomide-induced pulmonary fibrosis that was discovered after an intensive care unit (ICU) admission for severe Pseudomonas pneumonia...
June 2016: Eur J Rheumatol
Keisuke Goda, Tadakazu Takahashi, Akio Kobayashi, Toshiyuki Shoda, Hideyuki Kuno, Shoichiro Sugai
Drug-induced liver injury (DILI) is one of the serious and frequent drug-related adverse events. This adverse event is a main reason for regulatory action pertaining to drugs, including restrictions in clinical indications and withdrawal from clinical trials or the marketplace. Idiosyncratic DILI especially has become a major clinical concern because of its unpredictable nature, frequent hospitalization, need for liver transplantation and high mortality. The estimation of the potential for compounds to induce idiosyncratic DILI is very difficult in non-clinical studies because the precise mechanism of idiosyncratic DILI is still unknown...
2016: Journal of Toxicological Sciences
Matteo Cassina, Giulia A Cagnoli, Daniela Zuccarello, Elena Di Gianantonio, Maurizio Clementi
Exposure to teratogenic drugs during pregnancy is associated with a wide range of embryo-fetal anomalies and sometimes results in recurrent and recognizable patterns of malformations; however, the comprehension of the mechanisms underlying the pathogenesis of drug-induced birth defects is difficult, since teratogenesis is a multifactorial process which is always the result of a complex interaction between several environmental factors and the genetic background of both the mother and the fetus. Animal models have been extensively used to assess the teratogenic potential of pharmacological agents and to study their teratogenic mechanisms; however, a still open issue concerns how the information gained through animal models can be translated to humans...
September 14, 2016: European Journal of Medical Genetics
Tue Bjerg Bennike, Torkell Ellingsen, Henning Glerup, Ole Kristian Bonderup, Thomas Gelsing Carlsen, Michael Kruse Kruse Meyer, Martin Bøgsted, Gunna Christiansen, Svend Birkelund, Vibeke Andersen, Allan Stensballe
Rheumatoid arthritis (RA) is an inflammatory joint disease leading to cartilage damage and ultimately impaired joint function. To gain new insight into the systemic immune manifestations of RA, we characterized the colon mucosa proteome from 11 RA-patients and 10 healthy controls. The biopsies were extracted by colonoscopy and analyzed by label-free quantitative proteomics, enabling the quantitation of 5,366 proteins. The abundance of dihydrofolate reductase (DHFR) was statistically significantly increased in RA-patient biopsies compared to controls, and correlated with the administered dosage of methotrexate (MTX), the most frequently prescribed immunosuppressive drug for RA...
September 14, 2016: Journal of Proteome Research
F Yavuz, U Guzelkucuk
Leflunomide is an immunomodulatory agent with antiproliferative activity that is used for the treatment of rheumatoid arthritis. Leflunomide induced side effects are hepatotoxicity, immunosuppression, skin reactions, peripheral neuropathy, hypertension, diarrhea, interstitial lung disease, and rarely oral mucosal lesions. Here, we presented an unusual case of gingival overgrowth associated with the use of leflunomide, which improved after ceasing the drug.
April 2016: Acta Reumatológica Portuguesa
Firas El Chaer, Nobuyoshi Mori, Dimpy Shah, Nora Oliver, Emily Wang, Anna Jan, Vi Doan, Frank Tverdek, Jean Tayar, Ella Ariza-Heredia, Roy F Chemaly
Cytomegalovirus (CMV) reactivation is a clinically significant complication in hematopoietic stem cell transplant (HCT) recipients. Alternative therapy for multidrug-resistant CMV is limited and often fails. Leflunomide has been used to treat resistant CMV infections, however, data on efficacy, safety, and guidance for therapeutic drug level monitoring are lacking. In this report, we describe 3 HCT recipients with multi-drug resistant CMV infections who received leflunomide as adjuvant and salvage therapy. The therapeutic effect of leflunomide as an anti-CMV agent based on virologic responses and therapeutic drug monitoring were evaluated...
September 1, 2016: Antiviral Research
Glen S Hazlewood, Cheryl Barnabe, George Tomlinson, Deborah Marshall, Daniel J A Devoe, Claire Bombardier
BACKGROUND: Methotrexate is considered the preferred disease-modifying anti-rheumatic drug (DMARD) for the treatment of rheumatoid arthritis, but controversy exists on the additional benefits and harms of combining methotrexate with other DMARDs. OBJECTIVES: To compare methotrexate and methotrexate-based DMARD combinations for rheumatoid arthritis in patients naïve to or with an inadequate response (IR) to methotrexate. METHODS: We systematically identified all randomised controlled trials with methotrexate monotherapy or in combination with any currently used conventional synthetic DMARD , biologic DMARDs, or tofacitinib...
2016: Cochrane Database of Systematic Reviews
Isao Suzaki, Shuichi Kawano, Kosaku Komiya, Tsuyoshi Tanabe, Tomohiro Akaba, Kazuhito Asano, Harumi Suzaki, Kenji Izuhara, Bruce K Rubin
BACKGROUND AND OBJECTIVE: Serum periostin is increased in asthma and serves as a surrogate marker for IL-13 activity in the lung. Serum levels of periostin are the most robust biomarker predicting a favourable response to the anti-IL-13 drug, lebrikizumab. We investigated the mechanisms of IL-13 stimulation of periostin, the polarized secretion of periostin and whether periostin would have a direct effect on mucin secretion by airway cells. METHODS: Normal human bronchial epithelial (NHBE) cells were cultured at air-liquid interface (ALI) in the presence of IL-13, and we evaluated the effect of the specific inhibitors, leflunomide (Janus kinase (JAK)/signal transducer and activator of transcription factor 6 (STAT6) inhibitor) or PD98059 (MEK/extracellular regulated protein kinase (ERK) inhibitor), on periostin production...
August 24, 2016: Respirology: Official Journal of the Asian Pacific Society of Respirology
Jie Wu, Shu-Wei Duan, Xue-Feng Sun, Wen-Ge Li, Ya-Ping Wang, Wen-Hu Liu, Jian-Rong Zhang, Li-De Lun, Xue-Mei Li, Chun-Hua Zhou, Ji-Jun Li, Shu-Wen Liu, Yuan-Sheng Xie, Guang-Yan Cai, Lu Ma, Wen Huang, Hua Wu, Qiang Jia, Xiang-Mei Chen
BACKGROUND: The efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for immunoglobulin A nephropathy (IgAN) are unclear. This study was designed to evaluate the efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for IgAN. METHODS: It is a multicenter, prospective, double-dummy randomized controlled trial. Primary IgAN patients were recruited in 13 renal units across Beijing, China, from July 2010 to June 2012...
August 20, 2016: Chinese Medical Journal
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