HIGH-DOSE METHOTREXATE IN THE TREATMENT OF REFRACTORY JUVENILE RHEUMATOID-ARTHRITIS

Objective: To assess the response to and safety of long term, high dos e (greater than or equal to 1 mg/kg/week or greater than or equal to 1 5 mg/m(2)/week) methotrexate (MTX) administration, in a cohort of 21 c hildren with longstanding, severe juvenile rheumatoid arthritis (JRA). Methods: Children received MTX at an average weekly dose of 27 mg for a mean of 15.2 months. Outcome was assessed using a disease activity score based on changes in concomitant therapy, laboratory parameters, physician's global assessment and radiologic evaluation Results: Seven patients (33%) improved, including one child who achieved complete re mission, while 14/21 children (67%) did not benefit from high dose MTX . Subsequently, 6/14 (43%) of the non-responders discontinued high dos e MTX and began cyclosporine. Radiologic progression, regardless of cl inical outcome, was documented in 10/15 (67%) of the patients. The dru g was well tolerated despite mild gastrointestinal symptoms and transi ent liver enzyme elevation. Conclusion: The results of this open retro spective pilot trial suggest that high dose MTX is well tolerated but that its role in the treatment of children with refractory JRA may be limited Radiologic progression, despite improvement in the clinical st atus or in the laboratory parameters, supports the hypothesis that MTX acts as a potent antiinflammatory agent.