Methotrexate: a perspective of its use in the treatment of rheumatic diseases

MTX has been available for clinical use since 1951, and although it is widely accepted as a chemotherapeutic agent, its use in nonmalignant disorders has been sporadic and not well documented. Its mechanism of action is imprecisely understood but appears to involve both anti-inflammatory and immunosuppressive effects. The most extensive use of MTX in benign conditions has been in the treatment of psoriasis and more recently in psoriatic arthritis as well as polymyositis, sarcoid, and Reiter's syndrome. In addition, pilot studies have been carried out using MTX in patients with resistive RA. We have used MTX in 67 patients with severe RA. Maintained on oral pulse treatment schedule at 7.5 to 15.0 mg/week, approximately 75% had an improved global response with a significant decrease in active joints and ESR. Thirty-three patients have remained on therapy for periods of less than 1 year to more than 10 years. Thirty-four have discontinued treatment: 11 because of inefficacy, five with gastrointestinal complaints, three because of liver function abnormalities, and eight because of apprehension. Two patients died of neoplasm. Of the potential side effects of this agent, hepatotoxicity remains a serious consideration. We treat with attention to risk factors and rely on liver function tests to alert us to increased risk. There are data to suggest that a cumulative dose of MTX beyond 1.5 gm needs tissue surveillance. MTX appears to provide safe and effective treatment in resistive RA but requires further definitive trails.