High dose intravenous methotrexate with leucovorin rescue in rheumatoid arthritis.
ABSTRACT Five patients with severe, treatment refractory rheumatoid arthritis were treated with high dose intravenous methotrexate (500 mg/m2) followed by leucovorin (50 mg/m2). Four courses of chemotherapy were given over a 2-month interval. At the end of the final course, there was a 50% or greater improvement in joint swelling and pain indices and morning stiffness in all patients. Clinical responses persisted for 6-14 weeks posttherapy. High dose methotrexate-leucovorin was associated with a significant reduction in DR antigen expression on peripheral Leu 2, Leu 3 and Leu 4 lymphocytes.
- SourceAvailable from: Pieternella Maria HoutmanAnnals of the Rheumatic Diseases 09/1992; 51(8):1019-20. · 9.11 Impact Factor
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ABSTRACT: To assess the clinical usefulness of 2 novel therapies for treatment-resistant myositis. Thirty patients with refractory myositis, of whom 25 had an inadequate or no response to previous cytotoxic therapy, were randomized to begin either a combination of weekly oral methotrexate and daily azathioprine (MTX/AZA) or intravenous methotrexate with leucovorin rescue (I.V. MTX) every 2 weeks for 6 months. Crossover to the alternate therapy occurred according to defined rules; evaluations of muscle strength and functional abilities were performed at the beginning, and after 3 and 6 months, of each treatment. Of the 15 patients initially randomized to oral MTX/AZA, 8 improved with oral therapy and 1 improved with I.V. MTX during the crossover period. Of the 15 patients initially randomized to I.V. MTX therapy, 3 improved with the I.V. therapy and 4 with the oral combination during the crossover period. Although the study lacked the power to directly compare both treatments, intention-to-treat analysis showed a trend in favor of those patients who first received oral combination therapy (P = 0.025). There were 0.09 adverse events per patient-month with oral combination therapy and 0.16 per patient-month with I.V. therapy (P = 0.09). Combination oral MTX/AZA may benefit patients with treatment-resistant myositis, including those who previously had inadequate responses to either MTX or AZA alone. I.V. MTX with leucovorin rescue may also benefit some patients with refractory myositis.Arthritis & Rheumatology 03/1998; 41(3):392-9. · 7.48 Impact Factor
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ABSTRACT: Most studies of immune function in rheumatoid arthritis (RA) patients treated with methotrexate (MTX) show only marginal effects on humoral or cellular immune responses. These include measurements of lymphocyte subsets, proliferative responses to mitogens, immunoglobulin production, rheumatoid factor and immune complexes. The mechanism of action of MTX in RA might be more antiinflammatory than immunosuppressive. This is supported by the rapid clinical response to drug treatment and by data from in vitro and animal studies. The inhibition of interleukin-1 (IL-1) activity or other inflammatory cytokines by MTX may play an important role in the antiinflammatory effect of MTX. MTX effects in RA are not fully understood and further studies are needed to clarify its mechanism of action. MTX has crucial effects on the cascade of events initiated by some cytokines (IL-1, IL-6, tumor necrosis factor), which plays a major role in RA and other inflammatory diseases.Seminars in Arthritis and Rheumatism 01/1991; 20(3):190-200. · 3.81 Impact Factor