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Lower Methotrexate Doses for Rheumatoid Arthritis

Am Fam Physician. 2000 Mar 1;61(5):1493.

Low-dose oral methotrexate given weekly is currently considered the regimen of choice in patients with rheumatoid arthritis. Dosing was more frequent in the past, resulting in significantly more toxicity than the weekly regimen. Weekly dosing provides good disease control, is convenient and appears to result in lower toxicity. Little is known about the effectiveness of tapering the weekly dosage. Luis and associates compared the effectiveness of every-other-week (EOW) and weekly dosing regimens of methotrexate therapy in maintaining remission in patients with rheumatoid arthritis.

Patients with an established diagnosis of rheumatoid arthritis and a nine-month history of stable weekly methotrexate therapy were eligible for the prospective, randomized, single-blind study. Those who met the study criteria were stratified into one of four groups (methotrexate alone, methotrexate with chloroquine, methotrexate with prednisone or methotrexate with both agents) and then randomized to receive their established weekly dose or the EOW regimen. Patients were assessed at baseline, six, 12 and 24 months using multiple evaluation tools, including an examination by a rheumatologist who was blinded to the treatment protocols.

A total of 51 patients enrolled in the study, with 25 receiving the EOW regimen and 26 receiving weekly dosing. More than 90 percent of the patients remained in remission throughout the study, regardless of their treatment regimen. Two patients in the EOW group reverted back to weekly dosing for better symptom control. Overall, assessments at six and 12 months were similar between groups. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were comparable between groups at baseline but lower in the EOW group after six months; however, this finding was not clinically significant. The incidence of adverse reactions was also similar between groups, although the EOW group reported fewer gastrointestinal side effects and infections than the weekly dosing group.

The authors conclude that EOW dosing with methotrexate is a suitable alternative to the weekly regimen in patients with well-controlled rheumatoid arthritis. Patients tolerate the EOW regimen better, and it appears that EOW dosing has less effect on liver enzymes, although the authors caution that the difference may not be clinically important.

Luis M, et al. Comparison of two schedules for administering oral low-dose methotrexate (weekly versus every-other-week) in patients with rheumatoid arthritis in remission. A twenty-four–week, single-blind, randomized study. Arthritis Rheum. October 1999;42:2160–5.


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