Laboratory Biomarkers for Guiding Therapy with Methotrexate in Rheumatoid Arthritis

Title:Laboratory Biomarkers for Guiding Therapy with Methotrexate in Rheumatoid Arthritis

Volume: 21 Issue: 2

Author(s): Carlos Abud-Mendoza, Marco U. Martínez-Martínez, Adriana Monsivais-Urenda and Roberto Gonzalez- Amaro

Affiliation:

Keywords: Rheumatoid arthritis, immunosuppressive therapy, single nucleotide polymorphisms, adenosine, pharmacogenomics.

Abstract: Methotrexate (MTX) is a first-line drug for the treatment of several rheumatic diseases. However, it is difficult to predict the response to this drug based on clinical manifestations. Although different mechanisms of action have been proposed for the antiinflammatory and immunosuppressive effects of MTX, the best characterized are blockade of the de novo synthesis of purines and pyrimidines, which inhibits DNA synthesis, and induction of adenosine release, which downregulates the effector functions of different immune cells. Thus, variants of the enzymes and other molecules involved in these metabolic pathways are expected to play a relevant role in the therapeutic effect or toxicity of MTX in patients with rheumatoid arthritis (RA). Accordingly, polymorphisms of the genes encoding these proteins have been widely associated with the response to or discontinuation of MTX. In addition, variants of the genes involved in the transportation of MTX inside and outside cells and in its metabolism have also been associated with the efficacy or toxicity of this drug in patients with RA. However, published results are contradictory, and no consensus regarding the best laboratory markers of MTX efficacy has been reached. Therefore, additional prospective studies with a large number of patients are necessary to identify the combination of genetic and nongenetic factors that can predict, with a reasonable level of confidence, the efficacy and toxicity of MTX in patients with RA.

Cite this article as:

Abud-Mendoza Carlos, Martínez-Martínez U. Marco, Monsivais-Urenda Adriana and Gonzalez- Amaro Roberto, Laboratory Biomarkers for Guiding Therapy with Methotrexate in Rheumatoid Arthritis, Current Pharmaceutical Design 2015; 21 (2) . https://dx.doi.org/10.2174/1381612820666140825123632