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Use of Methotrexate in the Treatment of Inflammatory Bowel Diseases.

ABSTRACT: Low-dose methotrexate (MTX) therapy is a well-recognized therapy for many inflammatory conditions such as rheumatoid arthritis, psoriatic arthritis, and psoriasis. More than 20 years ago, the clinical efficacy of MTX was also established for steroid dependent Crohn's disease, but it was never broadly adapted as a treatment modality. More recently, MTX is being increasingly used in the pediatric population with Crohn's disease, both as a single agent as well as a concomitant therapy with anti-tumor necrosis factor-alpha treatment. This review outlines important pharmacological aspects for the therapeutic application of MTX and the current status of MTX as mono- or combination-therapy in both pediatric and adult patients with inflammatory bowel disease including new results of MTX monotherapy in steroid dependent ulcerative colitis.

SUBMITTER: Herfarth HH

PROVIDER: S-EPMC4679484 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Use of Methotrexate in the Treatment of Inflammatory Bowel Diseases.

Herfarth Hans H HH Kappelman Michael D MD Long Millie D MD Isaacs Kim L KL

Inflammatory bowel diseases 20160101 1

Low-dose methotrexate (MTX) therapy is a well-recognized therapy for many inflammatory conditions such as rheumatoid arthritis, psoriatic arthritis, and psoriasis. More than 20 years ago, the clinical efficacy of MTX was also established for steroid dependent Crohn's disease, but it was never broadly adapted as a treatment modality. More recently, MTX is being increasingly used in the pediatric population with Crohn's disease, both as a single agent as well as a concomitant therapy with anti-tum ...[more]

PMID: 26457382

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Project description:In this review, we provide an update on genome-wide association studies (GWAS) in inflammatory bowel disease (IBD). In addition, we summarize progress in defining the functional consequences of associated alleles for coding and noncoding genetic variation. In the small minority of loci where major association signals correspond to nonsynonymous variation, we summarize studies defining their functional effects and implications for therapeutic targeting. Importantly, the large majority of GWAS-associated loci involve noncoding variation, many of which modulate levels of gene expression. Recent expression quantitative trait loci (eQTL) studies have established that the expression of most human genes is regulated by noncoding genetic variations. Significant advances in defining the epigenetic landscape have demonstrated that IBD GWAS signals are highly enriched within cell-specific active enhancer marks. Studies in European ancestry populations have dominated the landscape of IBD genetics studies, but increasingly, studies in Asian and African-American populations are being reported. Common variation accounts for only a modest fraction of the predicted heritability and the role of rare genetic variation of higher effects (ie, odds ratios markedly deviating from 1) is increasingly being identified through sequencing efforts. These sequencing studies have been particularly productive in more severe very early onset cases. A major challenge in IBD genetics will be harnessing the vast array of genetic discovery for clinical utility through emerging precision medical initiatives. In this article, we discuss the rapidly evolving area of direct-to-consumer genetic testing and the current utility of clinical exome sequencing, especially in very early onset, severe IBD cases. We summarize recent progress in the pharmacogenetics of IBD with respect to partitioning patient responses to anti-TNF and thiopurine therapies. Highly collaborative studies across research centers and across subspecialties and disciplines will be required to fully realize the promise of genetic discovery in IBD.

Dataset Information

Use of Methotrexate in the Treatment of Inflammatory Bowel Diseases.

Publications

Use of Methotrexate in the Treatment of Inflammatory Bowel Diseases.

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