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.
