Objective To develop standardized treatment plans, clinical assessments, and response criteria for active, moderate to high severity juvenile localized scleroderma (jLS). Background jLS is a chronic inflammatory skin disorder associated with substantial morbidity and disability. Although a wide range of therapeutic strategies have been reported in the literature, a lack of agreement on treatment specifics and accepted methods for clinical assessment of have made it difficult to compare approaches and identify optimal therapy. Methods A core group of pediatric rheumatologists, dermatologists and a lay advisor was engaged by the Childhood Arthritis and Rheumatology Research Alliance (CARRA) to develop standardized treatment plans and assessment parameters for jLS using consensus methods/nominal group techniques. Recommendations were validated in two face-to-face conferences with a larger group of practitioners with expertise in jLS and with the full membership of CARRA, which encompasses the majority of pediatric rheumatologists in the U.S and Canada. Results Consensus was achieved on standardized treatment plans that reflect the prevailing treatment practices of CARRA members. Standardized clinical assessment methods and provisional treatment response criteria were also developed. Greater than 90% of pediatric rheumatologists responding to a survey (67% of CARRA membership) affirmed the final recommendations and agreed to utilize these consensus plans to treat patients with jLS. Conclusions Using consensus methodology, we have developed standardized treatment plans and assessment methods for jLS. The high level of support among pediatric rheumatologists will support future comparative effectiveness studies and enable the development of evidence-based guidelines for the treatment of jLS.
Objective. Intracellular methotrexate (MTX) polyglutamates (MTXGlu) have been shown to be potentially useful biomarkers of clinical response in adult patients with rheumatoid arthritis. The present study was undertaken to measure intracellular MTXGlu concentrations in a cohort of patients with juvenile idiopathic arthritis (JIA) to determine the predictors of MTXGlu variability in these patients.Methods. Blood samples were obtained from patients with JIA who were being treated with a stable dose of MTX for >3 months. Clinical data were collected by chart review. Concentrations of MTXGlu 1-7 in red blood cell lysates were quantitated using an innovative ionpairing chromatography procedure, with detection by mass spectrometry.Results
Objective. The response to and toxicity of methotrexate (MTX) are unpredictable in patients with juvenile idiopathic arthritis (JIA). Intracellular polyglutamation of MTX, assessed by measuring concentrations of MTX polyglutamates (MTXGlu), has been demonstrated to be a promising predictor of drug response. Therefore, this study was aimed at investigating the genetic predictors of MTXGlu variability and associations between MTXGlu and drug response in JIA.Methods. The study was designed as a singlecenter cross-sectional analysis of patients with JIA who were receiving stable doses of MTX at a tertiary care children's hospital. After informed consent was obtained from the 104 patients with JIA, blood was withdrawn during routine MTX-screening laboratory testing. Clinical data were collected by chart review. Genotyping for 34 single-nucleotide polymorphisms (SNPs) in 18 genes within the MTX metabolic pathway was performed. An ion-pair chromatographic procedure with mass spectrometric detection was used to measure MTXGlu 1-7 .Results. Analysis and genotyping of MTXGlu was completed in the 104 patients. K-means clustering resulted in 3 distinct patterns of MTX polyglutamation. Cluster 1 had low red blood cell (RBC) MTXGlu concentrations, cluster 2 had moderately high RBC MTXGlu 1 ؉ 2 concentrations, and cluster 3 had high concentrations of MTXGlu, specifically MTXGlu 3-5 . SNPs in the purine and pyrimidine synthesis pathways, as well as the adenosine pathway, were significantly associated with cluster subtype. The cluster with high concentrations of MTXGlu 3-5 was associated with elevated liver enzyme levels on liver function tests (LFTs), and there were higher concentrations of MTXGlu 3-5 in children who reported gastrointestinal side effects and had abnormal findings on LFTs. No association was noted between MTXGlu and active arthritis.Conclusion. MTXGlu remains a potentially useful tool for determining outcomes in patients with JIA being treated with MTX. The genetic predictors of MTXGlu variability may also contribute to a better understanding of the intracellular biotransformation of MTX in these patients.The response to methotrexate (MTX) in patients with juvenile idiopathic arthritis (JIA) is variable, with no identified predictors of response or toxicity (1-3). The mechanism of action of the drug is complex and incompletely understood. However, over the past several decades, we have gained increasing knowledge regarding specific sites of MTX action within the cellular folate cycle. Due to its inhibitory effect on several target enzymes, we know that MTX disrupts the folate cycle, which results in decreased production of DNA precursors, disruption of methyl-dependent reactions, and accumulation of adenosine, the latter of which has antiinflammatory properties (4-6).
Using consensus methodology, two standardized CTPs were developed for systemic immunosuppressive treatment of CAU. These CTPs are not meant as treatment guidelines, but are designed for further pragmatic research within the CARRA research network. Use of these CTPs in a prospective comparison effectiveness study should improve outcomes by identifying best practice options. This article is protected by copyright. All rights reserved.
BackgroundThere is not yet a commonly accepted, standardized approach in the treatment of juvenile idiopathic uveitis when initial steroid therapy is insufficient. We sought to assess current practice patterns within a large cohort of children with juvenile uveitis.MethodsThis is a cross-sectional cohort study of patients with uveitis enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRAnet) registry. Clinical information including, demographic information, presenting features, disease complications, and medications were collected. Chi-square and Fisher’s exact tests were used to assess for associations between medications and clinical characteristics.ResultsNinety-two children with idiopathic and 656 with juvenile idiopathic arthritis (JIA)-associated uveitis were identified. Indication (arthritis or uveitis) for medication use was not available for JIA patients; therefore, detailed analysis was limited to children with idiopathic uveitis. In this group, 94 % had received systemic steroids. Methotrexate (MTX) was used in 76 % of patients, with oral and subcutaneous forms given at similar rates. In multivariable analysis, non-Caucasians were more likely to be treated initially with subcutaneous MTX (P = 0.003). Of the 53 % of patients treated with a biologic DMARD, all received a tumor necrosis factor (TNF) inhibitor. TNF inhibitor use was associated with a higher frequency of cataracts (52 % vs 21 %; P = 0.001) and antinuclear antibody positivity (49 % vs 29 %; P = 0.04), although overall complication rates were not higher in these patients.ConclusionAmong idiopathic uveitis patients enrolled in the CARRAnet registry, MTX was the most commonly used DMARD, with subcutaneous and oral forms equally favored. Patients who received a TNF inhibitor were more likely to be ANA positive and have cataracts.Electronic supplementary materialThe online version of this article (doi:10.1186/s12969-016-0069-5) contains supplementary material, which is available to authorized users.
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