Methotrexate polyglutamates as a potential marker of adherence to long-term therapy in children with juvenile idiopathic arthritis and juvenile dermatomyositis: an observational, cross-sectional study.


INTRODUCTION:Methotrexate (MTX) is a cornerstone of treatment in a wide variety of inflammatory conditions, including juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM). However, owing to its narrow therapeutic index and the considerable interpatient variability in clinical response, monitoring of adherence to MTX is important. The present study demonstrates the feasibility of using methotrexate polyglutamates (MTXPGs) as a biomarker to measure adherence to MTX treatment in children with JIA and JDM. METHODS:Data were collected prospectively from a cohort of 48 children (median age 11.5 years) who received oral or subcutaneous (SC) MTX therapy for JIA or JDM. Dried blood spot samples were obtained from children by finger pick at the clinic or via self- or parent-led sampling at home, and they were analysed to determine the variability in MTXPG concentrations and assess adherence to MTX therapy. RESULTS:Wide fluctuations in MTXPG total concentrations (>2.0-fold variations) were found in 17 patients receiving stable weekly doses of MTX, which is indicative of nonadherence or partial adherence to MTX therapy. Age (P = 0.026) and route of administration (P = 0.005) were the most important predictors of nonadherence to MTX treatment. In addition, the study showed that MTX dose and route of administration were significantly associated with variations in the distribution of MTXPG subtypes. Higher doses and SC administration of MTX produced higher levels of total MTXPGs and selective accumulation of longer-chain MTXPGs (P < 0.001 and P < 0.0001, respectively). CONCLUSIONS:Nonadherence to MTX therapy is a significant problem in children with JIA and JDM. The present study suggests that patients with inadequate adherence and/or intolerance to oral MTX may benefit from SC administration of the drug. The clinical utility of MTXPG levels to monitor and optimise adherence to MTX in children has been demonstrated. TRIAL REGISTRATION:ISRCTN Registry identifier: ISRCTN93945409 . Registered 2 December 2011.


Arthritis Res Ther


Hawwa AF,AlBawab A,Rooney M,Wedderburn LR,Beresford MW,McElnay JC




Has Abstract


2015-10-22 00:00:00












  • Transcriptional profiling of bovine intervertebral disc cells: implications for identification of normal and degenerate human intervertebral disc cell phenotypes.

    abstract:INTRODUCTION:Nucleus pulposus (NP) cells have a phenotype similar to articular cartilage (AC) cells. However, the matrix of the NP is clearly different to that of AC suggesting that specific cell phenotypes exist. The aim of this study was to identify novel genes that could be used to distinguish bovine NP cells from A...

    journal_title:Arthritis research & therapy

    pub_type: 杂志文章


    authors: Minogue BM,Richardson SM,Zeef LA,Freemont AJ,Hoyland JA

    更新日期:2010-01-01 00:00:00

  • Differential expression of CD148 on leukocyte subsets in inflammatory arthritis.

    abstract:INTRODUCTION:Monocytic cells play a central role in the aetiology of rheumatoid arthritis, and manipulation of the activation of these cells is an approach currently under investigation to discover new therapies for this and associated diseases. CD148 is a transmembrane tyrosine phosphatase that is highly expressed in ...

    journal_title:Arthritis research & therapy

    pub_type: 杂志文章


    authors: Dave RK,Naylor AJ,Young SP,Bayley R,Hardie DL,Haworth O,Rider DA,Cook AD,Buckley CD,Kellie S

    更新日期:2013-01-01 00:00:00

  • Risk factors for cardiovascular mortality in patients with systemic lupus erythematosus, a prospective cohort study.

    abstract:INTRODUCTION:Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Cardiovascular disease (CVD) is common and a major cause of mortality. Studies on cardiovascular morbidity are abundant, whereas mortality studies focusing on cardiovascular outcomes are scarce. The aim of this study was to investigate cau...

    journal_title:Arthritis research & therapy

    pub_type: 杂志文章


    authors: Gustafsson JT,Simard JF,Gunnarsson I,Elvin K,Lundberg IE,Hansson LO,Larsson A,Svenungsson E

    更新日期:2012-01-01 00:00:00

  • What can chronic arthritis pain teach about developing new analgesic drugs?

    abstract::Chronic pain remains an important public health need with greater impact on the US economy than most other chronic conditions. Current pain management is largely limited to opioids and non-steroidal anti-inflammatory drugs, indicating a gap in the translation of new knowledge to the development of improved pain treatm...

    journal_title:Arthritis research & therapy

    pub_type: 社论


    authors: Witter J,Dionne RA

    更新日期:2004-01-01 00:00:00

  • Post-traumatic osteoarthritis following ACL injury.

    abstract::Post-traumatic osteoarthritis (PTOA) develops after joint injury. Specifically, patients with anterior cruciate ligament (ACL) injury have a high risk of developing PTOA. In this review, we outline the incidence of ACL injury that progresses to PTOA, analyze the role of ACL reconstruction in preventing PTOA, suggest p...

    journal_title:Arthritis research & therapy

    pub_type: 杂志文章,评审


    authors: Wang LJ,Zeng N,Yan ZP,Li JT,Ni GX

    更新日期:2020-03-24 00:00:00

  • The effect of risedronate on osteogenic lineage is mediated by cyclooxygenase-2 gene upregulation.

    abstract:INTRODUCTION:The purpose of this study was to evaluate the effects of risedronate (Ris) in the modulation of bone formation in rats with glucocorticoid (GC)-induced osteoporosis by histomorphometric, immunohistochemical and gene expression analyses. METHODS:We analyzed structure, turnover and microarchitecture, cycloo...

    journal_title:Arthritis research & therapy

    pub_type: 杂志文章


    authors: Valenti MT,Giannini S,Donatelli L,Zanatta M,Bertoldo F,Sella S,Vilei MT,Ossi E,Realdi G,Lo Cascio V,Dalle Carbonare L

    更新日期:2010-01-01 00:00:00

  • Elucidation of the potential roles of matrix metalloproteinases in skeletal biology.

    abstract::Irreversible destruction of joint structures is a major feature of osteoarthritis and rheumatoid arthritis. Fibrillar collagens in bone, cartilage and other soft tissues are critical for optimal joint form and function. Several approaches can be used to ascertain the role of collagenases, matrix metalloproteinases, in...

    journal_title:Arthritis research & therapy

    pub_type: 评论,社论


    authors: Krane SM

    更新日期:2003-01-01 00:00:00

  • Recent advances in the diagnosis and treatment of hemophagocytic lymphohistiocytosis.

    abstract::Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages secreting high amounts of inflammatory cytokines. It is a frequent manifestation in patients with predisposing genetic defects, but can o...

    journal_title:Arthritis research & therapy

    pub_type: 杂志文章,评审


    authors: Bode SF,Lehmberg K,Maul-Pavicic A,Vraetz T,Janka G,Stadt UZ,Ehl S

    更新日期:2012-06-08 00:00:00

  • Inhibition of inflammation but not ankylosis by glucocorticoids in mice: further evidence for the entheseal stress hypothesis.

    abstract:INTRODUCTION:Studies in the spontaneous ankylosis model in aging male DBA/1 mice and in patients with ankylosing spondylitis provide evidence that inflammation and new tissue formation leading to joint or spine ankylosis are likely linked but largely uncoupled processes. We previously proposed the 'entheseal stress' hy...

    journal_title:Arthritis research & therapy

    pub_type: 杂志文章


    authors: Braem K,Deroose CM,Luyten FP,Lories RJ

    更新日期:2012-03-12 00:00:00

  • TLR2 stimulation impairs anti-inflammatory activity of M2-like macrophages, generating a chimeric M1/M2 phenotype.

    abstract:BACKGROUND:Toll-like receptors (TLRs) and macrophages play an important role in rheumatoid arthritis (RA). Currently, it is not clear whether inflammatory M1 or anti-inflammatory M2 predominate among the resident macrophages in the synovium. In the present study, we set out to investigate the impact of TLR stimulation ...

    journal_title:Arthritis research & therapy

    pub_type: 杂志文章


    authors: Quero L,Hanser E,Manigold T,Tiaden AN,Kyburz D

    更新日期:2017-11-02 00:00:00

  • Interleukin-32 in systemic sclerosis, a potential new biomarker for pulmonary arterial hypertension.

    abstract:BACKGROUND:Pulmonary arterial hypertension (PAH) is a severe complication of systemic sclerosis (SSc), associated with a progressive elevation in pulmonary vascular resistance and subsequent right heart failure and death. Due to unspecific symptoms, the diagnosis of PAH is often delayed. On this basis, it is of great v...

    journal_title:Arthritis research & therapy

    pub_type: 杂志文章


    authors: Di Benedetto P,Guggino G,Manzi G,Ruscitti P,Berardicurti O,Panzera N,Grazia N,Badagliacca R,Riccieri V,Vizza CD,Radchenko G,Liakouli V,Ciccia F,Cipriani P,Giacomelli R

    更新日期:2020-06-01 00:00:00

  • IL-17A deficiency promotes periosteal bone formation in a model of inflammatory arthritis.

    abstract:BACKGROUND:Interleukin-17A (IL-17A) plays a pathogenic role in several rheumatic diseases including spondyloarthritis and, paradoxically, has been described to both promote and protect from bone formation. We therefore examined the effects of IL-17A on osteoblast differentiation in vitro and on periosteal bone formatio...

    journal_title:Arthritis research & therapy

    pub_type: 杂志文章


    authors: Shaw AT,Maeda Y,Gravallese EM

    更新日期:2016-05-10 00:00:00

  • Reduced Fas ligand-expressing splenic CD5+ B lymphocytes in severe collagen-induced arthritis.

    abstract:INTRODUCTION:The objective was to study immune regulation in a mouse model of rheumatoid arthritis that exhibits considerable heterogeneity of disease activity. METHODS:T-cell receptor transgenic mice, in which nearly all CD4+ T cells recognize a single peptide of type II collagen, were immunized with collagen and obs...

    journal_title:Arthritis research & therapy

    pub_type: 杂志文章


    authors: Lundy SK,Fox DA

    更新日期:2009-01-01 00:00:00

  • Soluble IL-18 receptor complex: a new star in the firmament of rheumatoid arthritis diagnosis?

    abstract::It has long been recognized that laboratory tests are useful in the diagnosis of disease and to monitor treatment outcome. Their performance has become even more demanding with the development of personalized medicine. In patients with rheumatoid arthritis (RA) the standard biochemical tests measure serological marker...

    journal_title:Arthritis research & therapy

    pub_type: 评论,社论


    authors: van de Loo FA

    更新日期:2011-04-27 00:00:00

  • Mapping of citrullinated fibrinogen B-cell epitopes in rheumatoid arthritis by imaging surface plasmon resonance.

    abstract:INTRODUCTION:Rheumatoid arthritis (RA) frequently involves the loss of tolerance to citrullinated antigens, which may play a role in pathogenicity. Citrullinated fibrinogen is commonly found in inflamed synovial tissue and is a frequent target of autoantibodies in RA patients. To obtain insight into the B-cell response...

    journal_title:Arthritis research & therapy

    pub_type: 杂志文章


    authors: van Beers JJ,Raijmakers R,Alexander LE,Stammen-Vogelzangs J,Lokate AM,Heck AJ,Schasfoort RB,Pruijn GJ

    更新日期:2010-01-01 00:00:00

  • An in vitro study investigating the survival and phenotype of mesenchymal stem cells following injection into nucleus pulposus tissue.

    abstract:INTRODUCTION:The decreased disc height characteristic of intervertebral disc (IVD) degeneration has often been linked to low back pain, and thus regeneration strategies aimed at restoring the disc extracellular matrix and ultimately disc height have been proposed as potential treatments for IVD degeneration. One such t...

    journal_title:Arthritis research & therapy

    pub_type: 杂志文章


    authors: Le Maitre CL,Baird P,Freemont AJ,Hoyland JA

    更新日期:2009-01-01 00:00:00

  • A novel function of artesunate on inhibiting migration and invasion of fibroblast-like synoviocytes from rheumatoid arthritis patients.

    abstract:INTRODUCTION:Anti-malarial drug artesunate can suppress inflammation and prevent cartilage and bone destruction in collagen-induced arthritis model in rats-suggesting it may be a potent drug for rheumatoid arthritis (RA) therapy. We aimed to investigate its effect on the invasive property of fibroblast-like synoviocyte...

    journal_title:Arthritis research & therapy

    pub_type: 杂志文章


    authors: Ma JD,Jing J,Wang JW,Yan T,Li QH,Mo YQ,Zheng DH,Gao JL,Nguyen KA,Dai L

    更新日期:2019-06-24 00:00:00

  • Interleukin (IL)-25 suppresses IL-22-induced osteoclastogenesis in rheumatoid arthritis via STAT3 and p38 MAPK/IκBα pathway.

    abstract:BACKGROUND:The present study aimed to evaluate the suppressive role of interleukin (IL)-25 in IL-22-induced osteoclastogenesis and receptor activator of nuclear factor κB ligand (RANKL) expression in rheumatoid arthritis (RA). METHODS:Serum from patients with RA and osteoarthritis (OA), and healthy controls, and synov...

    journal_title:Arthritis research & therapy

    pub_type: 杂志文章


    authors: Min HK,Won JY,Kim BM,Lee KA,Lee SJ,Lee SH,Kim HR,Kim KW

    更新日期:2020-09-23 00:00:00

  • JAG2/Notch2 inhibits intervertebral disc degeneration by modulating cell proliferation, apoptosis, and extracellular matrix.

    abstract:BACKGROUND:Intervertebral disc degeneration (IVDD)-related disorders are the major causes of low back pain. A previous study suggested that Notch activation serves as a protective mechanism and is a part of the compensatory response that maintains the necessary resident nucleus pulposus (NP) cell proliferation to repla...

    journal_title:Arthritis research & therapy

    pub_type: 杂志文章


    authors: Long J,Wang X,Du X,Pan H,Wang J,Li Z,Liu H,Li X,Zheng Z

    更新日期:2019-10-16 00:00:00

  • Levels of adiponectin, a marker for PPAR-gamma activity, correlate with skin fibrosis in systemic sclerosis: potential utility as biomarker?

    abstract:INTRODUCTION:Progressive fibrosis in systemic sclerosis (SSc) is linked to aberrant transforming growth factor beta (TGF-beta) signaling. Peroxisome proliferator-activated receptor gamma (PPAR-gamma) blocks fibrogenic TGF-beta responses in vitro and in vivo. Reduced expression and function of PPAR-gamma in patients wit...

    journal_title:Arthritis research & therapy

    pub_type: 杂志文章


    authors: Lakota K,Wei J,Carns M,Hinchcliff M,Lee J,Whitfield ML,Sodin-Semrl S,Varga J

    更新日期:2012-05-01 00:00:00

  • New developments in osteoarthritis. Posttraumatic osteoarthritis: pathogenesis and pharmacological treatment options.

    abstract::Joint trauma can lead to a spectrum of acute lesions, including osteochondral fractures, ligament or meniscus tears and damage to the articular cartilage. This is often associated with intraarticular bleeding and causes posttraumatic joint inflammation. Although the acute symptoms resolve and some of the lesions can b...

    journal_title:Arthritis research & therapy

    pub_type: 杂志文章,评审


    authors: Lotz MK,Kraus VB

    更新日期:2010-01-01 00:00:00

  • The HLA-B*35 allele modulates ER stress, inflammation and proliferation in PBMCs from Limited Cutaneous Systemic Sclerosis patients.

    abstract:INTRODUCTION:HLA-B*35 is associated with increased risk of developing pulmonary hypertension in SSc patients. We previously reported that HLA-B*35 induces endothelial cell dysfunction via activation of ER stress/UPR and upregulation of the inflammatory response. Because PBMCs from lcSSc-PAH patients are also characteri...

    journal_title:Arthritis research & therapy

    pub_type: 杂志文章


    authors: Lenna S,Assassi S,Farina GA,Mantero JC,Scorza R,Lafyatis R,Farber HW,Trojanowska M

    更新日期:2015-12-16 00:00:00

  • Statin-induced expression of CD59 on vascular endothelium in hypoxia: a potential mechanism for the anti-inflammatory actions of statins in rheumatoid arthritis.

    abstract::Hypoxia, which leads to dysfunctional cell metabolism, and complement activation both play central roles in the pathogenesis of rheumatoid arthritis (RA). Recent studies have reported that mice deficient for the complement-inhibitory protein CD59 show enhanced susceptibility to antigen-induced arthritis and reported t...

    journal_title:Arthritis research & therapy

    pub_type: 杂志文章


    authors: Kinderlerer AR,Steinberg R,Johns M,Harten SK,Lidington EA,Haskard DO,Maxwell PH,Mason JC

    更新日期:2006-01-01 00:00:00

  • Effect of Porphyromonas gingivalis infection on gut dysbiosis and resultant arthritis exacerbation in mouse model.

    abstract:BACKGROUND:Porphyromonas gingivalis (Pg) infection causes periodontal disease and exacerbates rheumatoid arthritis (RA). It is reported that inoculation of periodontopathogenic bacteria (i.e., Pg) can alter gut microbiota composition in the animal models. Gut microbiota dysbiosis in human has shown strong associations ...

    journal_title:Arthritis research & therapy

    pub_type: 杂志文章


    authors: Hamamoto Y,Ouhara K,Munenaga S,Shoji M,Ozawa T,Hisatsune J,Kado I,Kajiya M,Matsuda S,Kawai T,Mizuno N,Fujita T,Hirata S,Tanimoto K,Nakayama K,Kishi H,Sugiyama E,Kurihara H

    更新日期:2020-10-19 00:00:00

  • Frequency of Th17 CD20+ cells in the peripheral blood of rheumatoid arthritis patients is higher compared to healthy subjects.

    abstract:INTRODUCTION:Rheumatoid arthritis (RA) is considered a T cell driven autoimmune disease, therefore, the ability of B cell depleting biologics, e.g., anti-CD20 antibodies, to alleviate RA is unclear. This study examined the proportions of IL-17-secreting lymphocytes in the blood of healthy subjects and RA patients and d...

    journal_title:Arthritis research & therapy

    pub_type: 杂志文章


    authors: Eggleton P,Bremer E,Tarr JM,de Bruyn M,Helfrich W,Kendall A,Haigh RC,Viner NJ,Winyard PG

    更新日期:2011-01-01 00:00:00

  • Hypogalactosylation of immunoglobulin G in rheumatoid arthritis: relationship to HLA-DRB1 shared epitope, anticitrullinated protein antibodies, rheumatoid factor, and correlation with inflammatory activity.

    abstract:BACKGROUND:Galactosylation of immunoglobulin G (IgG) is reduced in rheumatoid arthritis (RA) and assumed to correlate with inflammation and altered humoral immunity. IgG hypogalactosylation also increases with age. To investigate dependencies in more detail, we compared IgG hypogalactosylation between patients with RA,...

    journal_title:Arthritis research & therapy

    pub_type: 杂志文章


    authors: Schwedler C,Häupl T,Kalus U,Blanchard V,Burmester GR,Poddubnyy D,Hoppe B

    更新日期:2018-03-14 00:00:00

  • Endothelin-1 in osteoarthritic chondrocytes triggers nitric oxide production and upregulates collagenase production.

    abstract::The mechanism of endothelin-1 (ET-1)-induced nitric oxide (NO) production, MMP-1 production and MMP-13 production was investigated in human osteoarthritis chondrocytes. The cells were isolated from human articular cartilage obtained at surgery and were cultured in the absence or presence of ET-1 with or without inhibi...

    journal_title:Arthritis research & therapy

    pub_type: 杂志文章


    authors: Manacu CA,Martel-Pelletier J,Roy-Beaudry M,Pelletier JP,Fernandes JC,Shipkolye FS,Mitrovic DR,Moldovan F

    更新日期:2005-01-01 00:00:00

  • Inflammation predicts accelerated brachial arterial wall changes in patients with recent-onset rheumatoid arthritis.

    abstract:INTRODUCTION:Patients with recent-onset rheumatoid arthritis (RA) have impaired brachial artery endothelial function compared with controls matched for age, sex and cardiovascular risk factors. The present study examined endothelium-dependent (flow-mediated dilatation (FMD)) and independent (glyceryl trinitrate (GTN)-m...

    journal_title:Arthritis research & therapy

    pub_type: 杂志文章


    authors: Hannawi S,Marwick TH,Thomas R

    更新日期:2009-01-01 00:00:00

  • Systematic protein-protein interaction and pathway analyses in the idiopathic inflammatory myopathies.

    abstract:BACKGROUND:The idiopathic inflammatory myopathies (IIM) are autoimmune diseases characterised by acquired proximal muscle weakness, inflammatory cell infiltrates in muscle and myositis-specific/associated autoantibodies. It is unclear which pathways are involved in IIM, and the functional relationship between autoantib...

    journal_title:Arthritis research & therapy

    pub_type: 杂志文章


    authors: Parkes JE,Rothwell S,Day PJ,McHugh NJ,Betteridge ZE,Cooper RG,Ollier WE,Chinoy H,Lamb JA,Myositis Genetics Consortium (MYOGEN).

    更新日期:2016-07-07 00:00:00

  • Very different performance of the power Doppler modalities of several ultrasound machines ascertained by a microvessel flow phantom.

    abstract:INTRODUCTION:In many patients with rheumatoid arthritis (RA) subclinical disease activity can be detected with ultrasound (US), especially using power Doppler US (PDUS). However, PDUS may be highly dependent on the type of machine. This could create problems both in clinical trials and in daily clinical practice. To cl...

    journal_title:Arthritis research & therapy

    pub_type: 杂志文章


    authors: Ten Cate DF,Luime JJ,van der Ven M,Hazes JM,Kooiman K,de Jong N,Bosch JG

    更新日期:2013-10-24 00:00:00