abstract details

The summaries are free for public use. ARTHROS will continue to add and archive summaries of articles deemed relevant to ARTHROS by our Faculty.

Methotrexate Mechanism in Treatment of Rheumatoid Arthritis

Author information

Friedman B1, Cronstein B2. Joint Bone Spine. 2018 Aug 3. pii: S1297-319X(18)30181-7. doi: 10.1016/j.jbspin.2018.07.004. [Epub ahead of print]

Abstract

Author information

1 Department of Medicine, New York University School of Medicine, New York, NY 10016, USA.

2 Department of Medicine, New York University School of Medicine, New York, NY 10016, USA. Electronic address: bruce.cronstein@med.nyu.edu.

Abstract

Methotrexate has been used in treatment of rheumatoid arthritis (RA) since the 1980s and to this day is often the first line medication for RA treatment. In this review, we examine multiple hypotheses to explain the mechanism of methotrexate efficacy in RA. These include folate antagonism, adenosine signaling, generation of reactive oxygen species (ROS), decrease in adhesion molecules, alteration of cytokine profiles, and polyamine inhibition amongst some others. Currently, adenosine signaling is probably the most widely accepted explanation for the methotrexate mechanism in RA given that methotrexate increases adenosine levels and on engagement of adenosine with its extracellular receptors an intracellular cascade is activated promoting an overall anti-inflammatory state. In addition to these hypotheses, we examine the mechanism of methotrexate in RA from the perspective of its adverse effects and consider some of the newer genetic markers of methotrexate efficacy and toxicity in RA. Lastly, we briefly discuss the mechanism of additive methotrexate in the setting of TNF-α inhibitor treatment of RA. Ultimately, finding a clear explanation for the pathway and mechanism leading to methotrexate efficacy in RA, there may be a way to formulate more potent therapies with fewer side effects.