Objective: To evaluate methotrexate treatment in patients with active adult onset Still's disease (AOSD). Methods: Methotrexate was initially given as a single weekly oral dose of 5 mg and adjusted individually afterwards in 13 patients with active AOSD. Symptoms and laboratory findings were investigated. Results: Signs of AOSD activity disappeared (remission) in eight patients between 3 and 16 weeks after starting methotrexate. In these patients, significant improvements in C reactive protein, erythrocyte sedimentation rate, white blood count, and serum ferritin were observed at 8, 12, 14, and 16 weeks after starting methotrexate, respectively. In six of these eight patients, steroids or non-steroidal anti-inflammatory drugs could be reduced or discontinued. In four patients methotrexate was not effective despite 12 or 16 weeks of treatment, and one patient discontinued treatment after 2 weeks because of severe nausea. Five patients suffered from adverse reactions, including acute interstitial pneumonia (one patient) and liver toxicity (two patients). Five out of eight patients successfully treated with methotrexate were HLA-DR4 positive (four homozygotes), and all the unsuccessfully treated patients were DR2 positive. Conclusions: Methotrexate is useful for controlling disease activity in AOSD, not only for refractory patients but also for patients who have never taken steroids or for those with steroid associated toxicity. However, serious adverse reactions can occur, as with rheumatoid arthritis. It is important to determine the critical factors, such as the immunogenetic background, that are associated with response to methotrexate treatment.
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