Ask the Experts - Methotrexate: Current Role in RA
What is the current role of methotrexate (MTX) in the management of rheumatoid arthritis (RA)? Does it have anti-inflammatory and analgesic effects? Should alcohol be restricted?

In the United States and many countries throughout the world, MTX has become the first-line disease-modifying antirheumatic drug (DMARD) therapy for many patients with RA. Over the past few decades, there has been a growing appreciation that RA can be a severe disease associated with substantial morbidity. Concomitantly, there has been interest in treating RA patients more aggressively. MTX has been the cornerstone of the modern therapeutic armamentarium. Not only is it the initial therapy for many patients with RA, it is also the most frequent agent on which combination therapies are
built, including the new tumor necrosis factor (TNF) inhibitors.

There are still questions related to the mechanisms of action of MTX in RA patients. Certainly, anti-inflammatory effects can be seen (mediated at least partly by modulation of adenosine release at inflammatory sites). A question remains regarding the extent to which MTX exerts immunosuppressive effects at the doses commonly used for patients with RA; this question has become more relevant with the trend toward higher doses of MTX. Regarding analgesia, the observed effects most likely derive secondarily from suppression of inflammation.

Among the factors that affect the potential toxicity of MTX, alcohol use has always been one that receives substantial consideration. While many physicians counsel patients to completely abstain from alcohol use while taking MTX, others recommend various degrees of restriction. Certainly, if patients choose to continue to use alcohol, they should accept the possibility that it might increase their chances of toxicity, particularly hepatic toxicity.