Low-dose methotrexate treatment of rheumatoid arthritis. Long-term observations

Of 21 patients with rheumatoid arthritis who began to receive low-dose weekly methotrexate up to five years ago, 15 (71 percent) have continued to take this drug for a mean of 42 months and have received a mean total dose of 2,021 mg (range: 915 to 3,075). The clinical improvement noted at the first follow-up (11 months) was sustained throughout this follow-up period (42 months). Three patients (14 percent) have had complete clinical remission and nine others (43 percent) have had an excellent response. Methotrexate was discontinued in four patients between the first and second follow-up because of planned pregnancy (one), gastrointestinal toxicity (two), and fear of toxicity (one). Liver toxicity assessed in these 21 patients and four others receiving long-term methotrexate therapy revealed acute hepatitis in one and elevated transaminase levels in 12 (48 percent). Liver biopsy specimens in 17 patients after a mean of 1,950 mg of methotrexate (range: 915 to 3,125) revealed mild fibrosis in six and no cirrhosis. Methotrexate can continue to suppress rheumatoid synovitis over a prolonged period of time with minimal toxicity in most patients. Hepatic fibrosis and cirrhosis due to methotrexate may be less common in rheumatoid arthritis than has been reported in psoriasis.