[Treatment with low-dose methotrexate in chronic polyarthritis. Review of the literature]

The therapeutic effect of low-dose MTX-treatment (10-25 mg/week) in active rheumatoid arthritis can be demonstrated by an improvement in clinical and laboratory parameters of disease activity already after 4-6 weeks. The mode of action is not fully understood. Direct anti-inflammatory effects seem to be more important than the weak immunosuppressive properties. Methotrexate treatment is indicated in all very active cases of rheumatoid arthritis, which do not respond to, or do not tolerate, conventional slow-acting antirheumatic drugs. In severe, rapidly progressing diseases MTX can be given without waiting for the effect of other disease modifying drugs. MTX is administered once a week i.v., i.m. or in one oral dose before breakfast. Absorption is reduced by food. The initial weekly dose is 15-25 mg and can be reduced to a minimum of 10 mg (7.5 mg) according to the clinical effect. A combination with antimalarials or gold salts is possible. The prescription of MTX is contraindicated in cases of renal function disturbances, active liver disease, bone marrow disturbances, active infectious diseases, pregnancy and excessive alcohol consumption. The most common side-effects are nausea and vomiting, stomatitis, transient elevations of transaminases. Rare conditions are leucopenia, thrombocytopenia and lung infiltrations. The side-effects are dose-related and disappear with dose reduction. They can be avoided by administering leucovorin 12 hours after giving MTX. Before starting the treatment total blood count with differential count and platelet count, serum creatinine and liver enzymes should be done. These laboratory studies have to be repeated every week for the first month, every two weeks up to the third month and every 1-2 months thereafter. When contraindications are considered and regular controls are made methotrexate is better tolerated than other cytotoxic agents. The rate of withdrawals is lower than with gold-treatment. In low-dose MTX-treatment drug interactions do not play a major role with normal renal function. Concomitant application of nonsteroidal antirheumatic drugs can delay MTX elimination and increase toxicity. We therefore avoid giving these drugs on the day of MTX-administration as far as possible.