Combination D-penicillamine and methotrexate therapy: proposal for early and aggressive treatment for rheumatoid arthritis.

We report a retrospective study of 16 patients with seropositive rheumatoid arthritis who were placed on combination D-penicillamine and methotrexate therapy for a period of 5-86 months. Three patients were lost to follow-up, and one patient died of unknown causes at another institution. Among the 12 remaining patients, there was no withdrawal secondary to drug intolerance. All patients demonstrated improvement in functional class correlated with a reduction in joint count, duration of morning stiffness, erythrocyte sedimentation rate, rheumatoid factor, and prednisone requirement. Eight of the 12 patients achieved remission as defined by the American College of Rheumatology criteria. Remission was sustained for a period of 3-72 months. The dosage of D-penicillamine ranged from 250-1000 mg/d (mean = 750 mg); that of methotrexate ranged from 5-15 mg/week (mean = 10 mg). The study indicates that D-penicillamine and methotrexate combination therapy is effective in the treatment of severe rheumatoid arthritis and warrants further prospective investigation.