Methotrexate: new mechanisms and old toxicities.

Over the last several years, information on methotrexate's mechanism(s) of action (which affects its efficacy) and toxicities continue to evolve. This popular second line agent (DMARD) is a potent anti-inflammatory drug, with effects on LTB4 and adenosine release (EC-50: 1-13 nM). As such, it may be a sufficiently potent anti-inflammatory drug to affect rheumatoid arthritis's basic course, as shown by a recent meta-analysis where methotrexate equalled gold and was better than azathioprine, when examining radiographic erosions. Its toxicities continue to be documented, with cirrhosis occurring between 2:100 and 1:1000 cases. Pneumonitis continues to be found. NSAID-MTX interactions, too, have been documented, although their kinetic mechanisms remain controversial.