Weekly Pulse Methotrexate in Rheumatoid Arthritis

Clinical and Immunologic Effects in a Randomized, Double-Blind Study

  1. PETER A. ANDERSEN, M.D.;
  2. STERLING G. WEST, M.D.;
  3. JAMES R. O'DELL, M.D.;
  4. CHARLES S. VIA, M.D.;
  5. ROBERT G. CLAYPOOL, M.D.; and
  6. BRIAN L. KOTZIN, M.D.
  1. Denver, Colorado; and San Antonio, Texas

    Abstract

    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.

    Article and Author Information

    • ▸From the Rheumatology Service, Department of Medicine, Fitzsimons Army Medical Center and the Rheumatology Section, Department of Medicine, Veterans Administration Medical Center, University of Colorado Health Sciences Center, Denver, Colorado; and the Rheumatology Service, Department of Medicine, Brooke Army Medical Center, San Antonio, Texas.

    • 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.

    • 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.

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