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Weekly Pulse Methotrexate in Rheumatoid Arthritis: Clinical and Immunologic Effects in a Randomized, Double-Blind Study

PETER A. ANDERSEN, M.D.; STERLING G. WEST, M.D.; JAMES R. O'DELL, M.D.; CHARLES S. VIA, M.D.; ROBERT G. CLAYPOOL, M.D.; and BRIAN L. KOTZIN, M.D.
[+] Article and Author Information

Grant support: in part by a grant from the Veterans Administration. Dr. Kotzin is a recipient of a Clinical Investigator award from the Veterans Administration.

Presented in part 6 June 1984 at the Annual Meeting of the American Rheumatism Association, Minneapolis, Minnesota.

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.

▸Requests for reprints should be addressed to Peter A. Andersen, M.D.; Rheumatology Service, Department of Medicine, Fitzsimons Army Medical Center; Aurora, CO 80045.


Denver, Colorado; and San Antonio, Texas


Ann Intern Med. 1985;103(4):489-496. doi:10.7326/0003-4819-103-4-489
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Twelve patients with refractory rheumatoid arthritis were treated with weekly pulse methotrexate in a double-blind, placebo-controlled, crossover study. After 13 weeks of therapy, patients receiving methotrexate showed greater improvement, judged by degree of joint swelling and tenderness, duration of morning stiffness, and subjective assessments of clinical condition, compared to those receiving placebo (p ≤ 0.002). This improvement was associated with a decrease in sedimentation rate and decreases in levels of IgG, IgM, and IgA; no changes were seen in serum rheumatoid factor titer or complement protein levels. Proportions of mononuclear cell subsets that were abnormal before treatment (decreased percentage of total T cells, increased percentage of monocytes) improved toward normal after therapy with methotrexate. However, no changes were seen in elevated pretreatment Leu-3/Leu-2 ratios, in in-vitro proliferative responses of lymphocytes to mitogens, or in immunoglobulin secretory responses to pokeweed mitogen. Weekly pulse methotrexate is effective in the short-term treatment of refractory rheumatoid arthritis. Little evidence for cellular immune suppression was associated with this clinical benefit.

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