Methotrexate in Rheumatoid Arthritis: Indications, Contraindications, Efficacy, and Safety

Evidence on the safety and efficacy of methotrexate as a second- or third-line agent for treating patients with rheumatoid arthritis is reviewed. Four placebo-controlled clinical trials have documented short-term benefit from methotrexate; although true remission is rare, patients receiving methotrexate showed a 26% (95% confidence interval [CI], 17% to 35%) greater improvement in their inflamed joint count and a 39% (95% CI, 26% to 51.5%) greater improvement in pain than did controls receiving nonsteroidal anti-inflammatory agents with or without prednisone. With respect to long-term benefit, improvement usually occurs within 1 month, reaching a maximum at 6 and then leveling off for the duration of treatment; in some patients, the benefit may wane after an initial satisfactory response in the first 4 to 6 months. In one third of those given methotrexate, treatment had to be discontinued because of adverse effects, less than 1% of which were life threatening. Careful baseline and follow-up monitoring is recommended until more data on the safety of methotrexate are available.

[1]  J. Kremer,et al.  Methotrexate metabolism analysis in blood and liver of rheumatoid arthritis patients. Association with hepatic folate deficiency and formation of polyglutamates. , 1986, Arthritis and rheumatism.

[2]  J. Kremer,et al.  The safety and efficacy of the use of methotrexate in long-term therapy for rheumatoid arthritis. , 1986, Arthritis and rheumatism.

[3]  Lee Wm,et al.  Hepatotoxicity after long-term methotrexate therapy. , 1986 .

[4]  Helen Daly,et al.  INTERACTION BETWEEN METHOTREXATE AND NON-STEROIDAL ANTI-INFLAMMATORY DRUGS , 1986, The Lancet.

[5]  M. Namer,et al.  CLINICAL AND PHARMACOKINETIC EVIDENCE OF A LIFE-THREATENING INTERACTION BETWEEN METHOTREXATE AND KETOPROFEN , 1986, The Lancet.

[6]  Furst De.  Clinical pharmacology of very low dose methotrexate for use in rheumatoid arthritis. , 1985 .

[7]  Kremer Jm.  Longterm methotrexate therapy in rheumatoid arthritis: a review. , 1985 .

[8]  W. Evans,et al.  Drug interactions with methotrexate. , 1985, The Journal of rheumatology. Supplement.

[9]  K. Tolman,et al.  Methotrexate and the liver. , 1985, The Journal of rheumatology. Supplement.

[10]  M. Weinblatt.  Toxicity of low dose methotrexate in rheumatoid arthritis. , 1985, The Journal of rheumatology. Supplement.

[11]  R. Snyderman,et al.  Pneumonitis complicating low-dose methotrexate therapy in rheumatoid arthritis. , 1985, Archives of internal medicine.

[12]  J. Lifson,et al.  Weekly pulse methotrexate in rheumatoid arthritis. Clinical and immunologic effects in a randomized, double-blind study. , 1985, Annals of internal medicine.

[13]  J. Korn,et al.  Low-dose methotrexate treatment of rheumatoid arthritis. Long-term observations. , 1985, The American journal of medicine.

[14]  M. Guttadauria,et al.  Comparison of low-dose oral pulse methotrexate and placebo in the treatment of rheumatoid arthritis. A controlled clinical trial. , 1985, Arthritis and rheumatism.

[15]  M. Weinblatt,et al.  Efficacy of low-dose methotrexate in rheumatoid arthritis. , 1985, The New England journal of medicine.

[16]  J. Esdaile,et al.  A controlled two-centre trial of parenteral methotrexate therapy for refractory rheumatoid arthritis. , 1984, The Journal of rheumatology.

[17]  N. Maruyama,et al.  Modified method for testing human natural thymocytotoxic antibody. , 1984, Arthritis and rheumatism.

[18]  M. Guttadauria,et al.  Randomized, double-blind, placebo controlled trial of low-dose pulse methotrexate in psoriatic arthritis. , 1984, Arthritis and rheumatism.

[19]  F. Jamali,et al.  Low‐dose methotrexate kinetics in arthritis , 1984, Clinical pharmacology and therapeutics.

[20]  R T Hoffmeister,et al.  Methotrexate therapy in rheumatoid arthritis: 15 years experience. , 1983, The American journal of medicine.

[21]  T. Taylor,et al.  Low dose oral methotrexate in rheumatoid arthritis: an uncontrolled trial and review of the literature. , 1983, Seminars in arthritis and rheumatism.

[22]  A. Russell,et al.  Methotrexate levels, a guide to therapy? , 1983, Clinical and experimental rheumatology.

[23]  P Tugwell,et al.  Preference for endpoint measures in clinical trials: results of structured workshops. , 1982, The Journal of rheumatology.

[24]  A. Sliwinski,et al.  Weekly intravenous methotrexate in the treatment of rheumatoid arthritis. , 1982, Arthritis and rheumatism.

[25]  H. Maibach,et al.  Methotrexate guidelines--revised. , 1982, Journal of the American Academy of Dermatology.

[26]  D. Mitchell,et al.  Preliminary criteria for clinical remission in rheumatoid arthritis. , 1981, Arthritis and rheumatism.

[27]  T C Chalmers,et al.  A method for assessing the quality of a randomized control trial. , 1981, Controlled clinical trials.

[28]  Willkens Rf,et al.  Low dose pulse methotrexate therapy in rheumatoid arthritis. , 1980 .

[29]  D. Sackett,et al.  Controversy in counting and attributing events in clinical trials. , 1979, The New England journal of medicine.

[30]  V. Jones,et al.  Intra-articular methotrexate. Clinical and laboratory study in rheumatoid and psoriatic arthritis. , 1978, Annals of the rheumatic diseases.

[31]  A. Nyfors.  Liver biopsies from psoriatics related to methotrexate therapy. 3. Findings in post-methotrexate liver biopsies from 160 psoriatics. , 2009, Acta pathologica et microbiologica Scandinavica. Section A, Pathology.

[32]  E. Ring,et al.  Comparison of intra-articular methotrexate with intra-articular triamcinolone hexacetonide by thermography. , 1977, Current medical research and opinion.

[33]  M. D. Hogan,et al.  Is methotrexate therapy for psoriasis carcinogenic? A modified retrospective-prospective analysis. , 1975, JAMA.

[34]  H. Maibach,et al.  Psoriasis-liver-methotrexate interactions. , 1973, Archives of dermatology.

[35]  G. Weinstein,et al.  Methotrexate for psoriasis. A new therapeutic schedule. , 1971, Archives of dermatology.

[36]  R. Gubner,et al.  THERAPEUTIC SUPPRESSION OF TISSUE REACTIVITY: II. Effect of Aminopterin in Rheumatoid Arthritis and Psoriasis , 1951, The American journal of the medical sciences.