Methotrexate

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Methotrexate is a folic acid antagonist derived from aminopterin. It inhibits dihydrofolate reductase, the enzyme required in the pathway supplying methyl donor groups for DNA, RNA and protein synthesis. Methotrexate has been used for the treatment of diseases characterised by inflammation or cellular proliferation. In 1985 the first randomised, placebo-controlled trials were published that demonstrated the short-term efficacy of low-dose weekly methotrexate in rheumatoid arthritis (RA). Methotrexate is now the most widely used disease-modifying antirheumatoid drug (DMARD) in the developed world. It was first used in the treatment of psoriatic arthritis (PsA) in 1951, and has been shown to be of clinical benefit in this condition.
However, methotrexate toxicity remains an important issue when considering its use, and is one of the main reasons for discontinuation. The most common adverse effects are gastrointestinal, such as anorexia, nausea, stomatitis and diarrhoea. CNS toxicity including headache, dizziness, fatigue and mood disturbance may occur. Haematological toxicity is not common, and although all types of cytopenia have been documented, an identifiable risk factor can usually be found, such as untreated folate deficiency, renal insufficiency or superimposed infection.

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