Proposition: methotrexate should not be the first second-line agent to be used in rheumatoid arthritis if NSAIDs fail.

Although methotrexate (MTX) is an effective antirheumatic drug, it cannot clearly be defined as a disease modifying antirheumatic drug (DMARD), when this term is characterized by its effect on radiographs or laboratory data. Current data, in the form of small studies or case reports, show that MTX's hepatic toxicity is not yet fully defined, that its acute pulmonary toxicity is significant, that systemic fungal infections may be associated with MTX use in rheumatoid arthritis (RA), that unexplained significant weight loss can be a problem, and that the consequence of drug interactions with MTX are not yet fully known. Thus, although clearly an effective antiinflammatory drug in RA, the place of MTX in the RA armamentarium is not fully defined. For this reason, MTX should not at present be used as the first second-line agent in RA after nonsteroidal antiinflammatory drugs (NSAIDs) fail.