Serum Osteopontin as a Predictive Marker of Responsiveness to Methotrexate in Juvenile Idiopathic Arthritis

Masi, Laura; Ricci, Luisa; Zulian, Francesco; Monte, Francesca Del; Simonini, Gabriele; Serena, Capannini; Martino, Maurizio de; Brandi, Maria Luisa; Falcini, Fabio

doi:10.3899/jrheum.081156

Cited by 8 publications

(4 citation statements)

References 21 publications

(18 reference statements)

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“…Another candidate predictor, osteopontin, is expressed by natural killer cells and activated T cells, and plays a role in the production of pro-inflammatory cytokines. It is overexpressed in synovial T cells in patients with rheumatoid arthritis, demonstrating its role in inflammatory arthritis [ 26 ]. The theoretical background of these candidate predictors may increase the likelihood that they really affect MTX efficacy, however, it should be kept in mind that the found associations do not prove a causal effect.…”

Section: Discussionmentioning

confidence: 99%

Prediction of methotrexate efficacy and adverse events in patients with juvenile idiopathic arthritis: a systematic literature review

Dijkhuizen

Wulffraat

2014

Pediatr Rheumatol

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BackgroundMethotrexate (MTX) is the cornerstone disease-modifying anti-rheumatic drug in juvenile idiopathic arthritis (JIA). In JIA, it is important to start effective treatment early to avoid long-term sequelae, such as joint damage. To accomplish this goal, it is crucial to know beforehand who is going to respond well to MTX. In addition, MTX adverse effects such as MTX intolerance occur frequently, potentially hindering its efficacy. To avoid inefficacy of an otherwise effective drug, the physician should be timely aware of these adverse events. Consequently, to optimise treatment of JIA patients with MTX, predictors for efficacy and adverse events should be used in daily clinical practice. The aim of this study was to summarise the existing knowledge about such predictors.MethodsA systematic literature search was performed in PubMed, Embase and The Cochrane Library, and 1,331 articles were identified. These were selected based on their relevance to the topic and critically appraised according to pre-defined criteria. Predictors for MTX efficacy and adverse events were extracted from the literature and tabulated.ResultsTwenty articles were selected. The overall quality of the studies was good. For MTX efficacy, candidate predictors were antinuclear antibody positivity, the childhood health assessment questionnaire score, the myeloid-related protein 8/14 level, long-chain MTX polyglutamates, bilateral wrist involvement and some single nucleotide polymorphisms (SNPs) in the adenosine triphosphate binding cassette and solute carrier transporter gene families. For MTX adverse events, potential predictors were alanine aminotransferase and thrombocyte level and two SNPs in the γ-glutamyl hydrolase and methylenetetrahydrofolate reductase genes. However, validation of most predictors in independent cohorts was still lacking.ConclusionsInteresting candidate predictors were found, especially for MTX efficacy. However, most of these were not validated. This should be the goal of future efforts. A clinically relevant way to validate the predictors is by means of creating a clinical prediction model.Electronic supplementary materialThe online version of this article (doi:10.1186/1546-0096-12-51) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Prediction of methotrexate efficacy and adverse events in patients with juvenile idiopathic arthritis: a systematic literature review

Dijkhuizen

Wulffraat

2014

Pediatr Rheumatol

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“…20 Increased expression of OPN in the tissue is reflected by elevated concentrations of OPN in plasma and increased OPN levels are clearly not specific for MS, but increased in parallel in patients with inflammatory and non-inflammatory neurological diseases. 21,22 In addition, OPN serum or plasma levels increase in a variety of non-neurological conditions, such as disseminated carcinomas of the breast, lung and prostate; 23,24 arthritis; 25,26 asthma; 27 psoriasis; 28 cardiovascular disease 29–31 and smoking, 32 raising doubts about the usefulness of OPN levels as a biomarker for disease activity in MS in an unselected population.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of circulating osteopontin levels in an unselected cohort of patients with multiple sclerosis: relevance for biomarker development

et al. 2013

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“…Osteopontin (OPN) is a pleiotropic proinflammatory cytokine promoting chronic inflammatory processes in various systemic autoimmune diseases such as RA, juvenile idiopathic arthritis, SLE, systemic sclerosis and multiple sclerosis [85][86][87][88][89][90]. In RA, where high levels of OPN are supposed to play a role in bone erosion, the presence of anti-OPN AAbs has been described and was inversely correlated with biological markers of disease activity [91].…”

Section: Anti-osteopontin Autoantibodiesmentioning

confidence: 99%

Emerging clinical phenotypes associated with anti-cytokine autoantibodies

Vincent

Plawecki

Goulabchand

et al. 2015

Autoimmunity Reviews

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Serum Osteopontin as a Predictive Marker of Responsiveness to Methotrexate in Juvenile Idiopathic Arthritis

Abstract: Serum levels of OPN at baseline represent a possible marker to predict the responsiveness to MTX in patients with JIA.

Cited by 8 publications

References 21 publications

Prediction of methotrexate efficacy and adverse events in patients with juvenile idiopathic arthritis: a systematic literature review

Prediction of methotrexate efficacy and adverse events in patients with juvenile idiopathic arthritis: a systematic literature review

Evaluation of circulating osteopontin levels in an unselected cohort of patients with multiple sclerosis: relevance for biomarker development

Emerging clinical phenotypes associated with anti-cytokine autoantibodies

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