Inflammopharmacology

, Volume 26, Issue 3, pp 699–708 | Cite as

Predicting methotrexate resistance in rheumatoid arthritis patients

  • Mary Beth Yu
  • Anthony Firek
  • William H. R. Langridge
Review
  • 121 Downloads

Abstract

Rheumatoid arthritis (RA) is an incurable, systemic autoimmune disease that decreases quality of life and can lead to severe disability. While there are many medications available to treat RA, the first-line of therapy is low-dose methotrexate (MTX), a small molecule disease-modifying anti-rheumatic drug (DMARD). MTX is the recommended therapy due to its affordability and efficacy in reducing symptoms in most RA patients. Unfortunately, there is great person-to-person variability in the physiological response to MTX, with up to 50% of patients showing little response to the medication. Thus, many RA patients initially placed on MTX do not experience an adequate reduction of symptoms, and could have benefited more in both the short and long terms if initially prescribed a different drug that was more effective for them. To combat this problem and better guide treatment decisions, many research groups have attempted to develop predictive tools for MTX response. Currently, there is no reliable, clinical-grade method to predict an individual’s response to MTX treatment. In this review, we describe progress made in the area of MTX non-response/resistance in RA patients. We specifically focus on application of the following elements as predictive markers: proteins related to MTX transport and function, intracellular MTX concentration, immune cell frequencies, cytokines, and clinical factors.

Keywords

Rheumatoid arthritis Methotrexate Response Resistance Predict 

Abbreviations

ABC

ATP binding cassette

ACPA

Anti-citrullinated protein antibody

ACR

American College of Rheumatology

ADA

Adenosine deaminase

AICAR

Aminoimidazole carboxamide ribonucleotide

AMPDA

AMP deaminase

ATIC

Aminoimidazole carboxamide ribonucleotide transformylase

BCRP

Breast cancer resistance protein

DC

Dendritic cell

DHF

Dihydrofolate

DHFR

Dihydrofolate reductase

DMARD

Disease-modifying anti-rheumatic drug

EULAR

European League Against Rheumatism

IC50

Half maximal inhibitory concentration

KM

Michaelis constant

MDR

Multidrug Resistance Protein

MRP

Multidrug resistance-associated protein

MTX

Methotrexate

MTX-PG

Polyglutamated methotrexate

NSAID

Nonsteroidal anti-inflammatory drug

PBMC

Peripheral blood mononuclear cells

PCFT

Proton-coupled folate transporter

PKA

Protein kinase A

PMN

Polymorphonuclear leukocytes

RA

Rheumatoid arthritis

RF

Rheumatoid factor

RFC

Reduced folate carrier

SE

Shared epitope

SLC

Solute carrier

THF

Tetrahydrofolate

TNFR

TNF receptor

TYMS

Thymidylate synthetase

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Basic Sciences, Center for Health Disparities and Molecular MedicineLoma Linda University School of MedicineLoma LindaUSA
  2. 2.Section of EndocrinologyRiverside University Health System Medical CenterMoreno ValleyUSA

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