Historical perspective on the use of methotrexate for the treatment of rheumatoid arthritis.

Aminopterin, a folic acid analogue was first reported in 1948 to produce temporary remission of acute leukemia of children, was also reported in 1951 to produce an important and rapid improvement in patients with rheumatoid arthritis (RA) and psoriasis. By 1972, low dose pulse methotrexate was observed to be useful in RA, but it was not until 1980 that additional beneficial effects of methotrexate in the treatment of patients with refractory RA appeared in the literature. Subsequently, both uncontrolled experience and double blind prospective trials have demonstrated efficacy and acceptable tolerability and safety of methotrexate in the treatment of patients with RA. Guidelines for its use in patients with RA still need to be developed.