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Diagnosis and Treatment |

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

PETER TUGWELL, M.D.; KATHRYN BENNETT, M.Sc.; and MICHAEL GENT, M.Sc.
[+] Article and Author Information

▸Requests for reprints should be addressed to Peter Tugwell, M.D.; Department of Clinical Epidemiology and Biostatistics, McMaster University, Room 2C16, 1200 Main Street, West; Hamilton, Ontario L8N 3Z5, Canada.


Hamilton, Ontario, Canada


© 1987 American College of PhysiciansAmerican College of Physicians


Ann Intern Med. 1987;107(3):358-366. doi:10.7326/0003-4819-107-2-358
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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; combining the four studies using meta-analysis shows that, although true remission is rare, patients receiving methotrexate had a 26% (95% confidence interval [Cl], 17% to 35%) greater improvement in their inflamed joint count and a 39% (95% Cl, 26% to 51.5%) greater improvement in pain than did controls receiving nonsteroidal anti-inflammatory agents with or without prednisone. With respect to longterm 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.

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