Methotrexate: its use in the rheumatic diseases.

Area of Science:

• Rheumatology
• Pharmacology

Background:

• Methotrexate (MTX) is increasingly used for refractory psoriatic arthritis, polymyositis, Reiter's disease, and rheumatoid arthritis.
• As a folate antagonist, MTX inhibits DNA synthesis, exerting immunosuppressive and anti-inflammatory effects.
• Its precise mechanisms in rheumatic diseases and potential drug interactions require further elucidation.

Purpose of the Study:

• To review the efficacy and safety of low-dose intermittent methotrexate in rheumatic diseases.
• To highlight the pharmacokinetic properties and potential toxicities of methotrexate therapy.
• To assess the current evidence supporting methotrexate as a preferred immunosuppressive agent.

Main Methods:

• Literature review of clinical studies on methotrexate in rheumatic diseases.
• Analysis of pharmacokinetic data, including absorption, metabolism, and drug interactions.
• Evaluation of reported short-term and long-term adverse events, including liver and pulmonary toxicity.

Main Results:

• Methotrexate demonstrates efficacy in various rheumatic conditions, with fewer short-term side effects than other immunosuppressants.
• Variable absorption and potential antagonism by folate supplements can affect MTX efficacy.
• Long-term toxicity includes liver fibrosis/cirrhosis, increasing with cumulative dose and duration; hypersensitivity pneumonitis is also a concern.

Conclusions:

• Low-dose methotrexate is a valuable therapeutic option for specific rheumatic diseases.
• Careful monitoring for long-term toxicities, particularly liver and pulmonary, is crucial.
• Further prospective, double-blind controlled studies are needed to solidify methotrexate's role as a first-line immunosuppressive.