[Low dose methotrexate therapy in chronic polyarthritis--an update]

Since the early eighties methotrexate (MTX) has become of increasing importance in long-term therapy of rheumatoid arthritis (RA) as a disease modifying drug (DMARD). Nowadays it is probably the most frequently prescribed DMARD for RA and can be regarded as the gold standard in long-term therapy. MTX can be administered orally or parenterally, the bioavailability shows high individual differences, but is about 70% after oral administration on average. Its protein-binding amounts to 50%, the main pathway of elimination is renal tubular secretion, to a smaller extent also biliary excretion. MTX polyglutamates are stored intracellularly. Its mode of action in RA is not completely elucidadet yet, besides inhibition of dihydrofolatereductase and consequently inhibition of thymidilate synthesis, some antiinflammatory effects, such as stimulation of Adenosine release from neutrophils, may contribute to the therapeutical effects. MTX' efficacy could be proven by several controlled trials, some of them lasting for more than five years. During long-term therapy with MTX a folate deficiency may occur, which can lead to some side effects. Most important but rarely occurring is pneumonitis, moreover hepatotoxicity and hematological features have to be intensively considered. The risk of the development of osteopenia or an increased incidence of malignancies during MTX therapy is currently investigated. In case of clinical and laboratory controls at regular intervals and patient education MTX therapy can be regarded as effective, well tolerable and considerably safe for patients with rheumatoid arthritis.