Showing papers in "The Journal of Rheumatology Supplement in 1985"

Toxicity of low dose methotrexate in rheumatoid arthritis.

Abstract: The efficacy and acceptability of low dose weekly methotrexate therapy in rheumatoid arthritis was reviewed in 587 patients in open and randomized trials. Gastrointestinal toxicity was reported most frequently. Bone marrow suppression, stomatitis, alopecia, headaches, and fever also occurred. A review of these adverse reactions, as well as of the effects of this drug on the reproductive, renal, and pulmonary systems, is discussed.

Methotrexate and the liver.

Abstract: The findings of liver studies in 29 patients who were treated with low dose pulse methotrexate for rheumatoid arthritis (RA) are described. The biopsy specimens of 22 patients (76%) showed liver abnormalities, but cirrhosis did not develop in any patient. There were no statistically significant differences in age, duration of treatment, or cumulative dose between patients in whom abnormal liver histology developed and those in whom it did not. Our findings showed that isolated elevations of the aminotransferase enzymes or alkaline phosphatase levels did not predict liver disease, nor did the absence of elevation of these enzymes assure the absence of liver disease. Serial elevations of the aminotransferase and/or alkaline phosphatase enzyme levels and the development of hypoalbuminemia during treatment were specific indicators of the development of liver disease. In the patients studied, significant liver disease did not develop before 2 years of therapy or with a cumulative dose of methotrexate of less than 1500 mg.

Drug interactions with methotrexate.

Abstract: General mechanisms of drug interactions are reviewed, as well as the effects of various drugs on the absorption, distribution, protein binding, eliminations and cellular transport of methotrexate. Published studies demonstrate that prior or concomitant administration of other drugs can alter the efficacy and toxicity of methotrexate. Nonabsorbable antibiotics can decrease methotrexate absorption. Nephrotoxic drugs can decrease methotrexate renal clearance. Salicylates and probenecid may decrease the plasma protein binding and renal tubular secretion of methotrexate. However, the clinical significance of many of these drug interactions is not known or has not been substantiated by extensive clinical observations.

Historical perspective on the use of methotrexate for the treatment of rheumatoid arthritis.

Abstract: Aminopterin, a folic acid analogue was first reported in 1948 to produce temporary remission of acute leukemia of children, was also reported in 1951 to produce an important and rapid improvement in patients with rheumatoid arthritis (RA) and psoriasis. By 1972, low dose pulse methotrexate was observed to be useful in RA, but it was not until 1980 that additional beneficial effects of methotrexate in the treatment of patients with refractory RA appeared in the literature. Subsequently, both uncontrolled experience and double blind prospective trials have demonstrated efficacy and acceptable tolerability and safety of methotrexate in the treatment of patients with RA. Guidelines for its use in patients with RA still need to be developed.

Clinical pharmacology of very low dose methotrexate for use in rheumatoid arthritis.

Abstract: The clinical pharmacokinetics of methotrexate, particularly when the drug is used at low doses for nonmalignant disease, are complicated and require extensive study. Bioavailability of the drug may be influenced--at least in part--by food intake. Biliary excretion can compensate for decreased renal excretion of methotrexate to some degree. However, further studies of the renal excretion of methotrexate are needed.

Longterm methotrexate therapy in rheumatoid arthritis: a review.

Abstract: A review of the literature on the longterm use of methotrexate in patients with rheumatoid arthritis (RA) showed that many questions on protocol remain unanswered. Although rheumatologists have adopted certain guidelines previously followed by dermatologists for psoriasis patients, rheumatology literature offers no set of rules for using the drug in treating patients with RA. The use of liver function tests and liver biopsy specimens to predict and assess hepatotoxicity associated with methotrexate use is also discussed.

Short term efficacy of methotrexate in the treatment of rheumatoid arthritis.

Abstract: Methotrexate is easily administered, widely accepted by patients, and has a rapid therapeutic effect. With careful attention to known risk factors, such as alcoholism, diabetes, obesity, and renal disease, it is a useful agent for the treatment of refractory rheumatoid arthritis (RA). Although rheumatologists have been using methotrexate in the treatment of RA for some time, controlled studies have been needed to establish the safety and efficacy of this agent. This paper will review the findings of the Cooperating Clinics of the American Rheumatism Association, as well as other studies that have investigated the short term efficacy of methotrexate.

The immunopathogenesis of rheumatoid arthritis.

Abstract: Rheumatoid arthritis (RA) may represent a T cell dependent immune response to a restricted antigen(s) within the joint, with inflammatory pathways reflecting secondary recruitment. The nature of the inciting antigen is unknown--the stimulus could be an infectious agent or a host constituent. In patients with RA, the centrality of antiself reactivities and immunogenetic influences is apparent. Further clarification of these mechanisms would result in a potential for antigen-specific immunosuppressive therapy.