In the U.S, methotrexate remains the cornerstone of treatment for RA. Its exact mechanism of action is unclear, but its anti-folate effect contributes to its effect as a potent anti-inflammatory agent. It has a more rapid onset of action than many of the older DMARDs. Although it has many potential toxicities, most are reversible when the drug is stopped. These include bone marrow suppression, stomatitis, nausea, alopecia and hepatic toxicity. Idiopathic pulmonary hypersensitivity is perhaps the most dangerous side effect and must be dealt with promptly to avoid serious impairments. Because of these toxicities, methotrexate must be monitored carefully.
Reference: Hochberg MC (ed). Rheumatology, 3rd ed. St. Louis, Mosby, 2003