Low-dose D-penicillamine therapy in rheumatoid arthritis. A controlled, double-blind clinical trial. Clinical evaluation of D-penicillamine by multicentric double-blind comparative study in chronic rheumatoid arthritis.
Two hundred twenty-five patients with active severe rheumatoid arthritis were admitted to a multiclinic, controlled, double-blind trial comparing the use of 500 mg D-penicillamine per day, 125 mg D-penicillamine per day, and placebo. One hundred seventy-one patients completed at least 30 weeks of therapy. The 500 mg D-penicillamine group demonstrated statistically significant improvement over the placebo group in grip strength, average circumference of swollen proximal interphalangeal joints, and patient assessment. While the trend was for greater improvement with the larger dose of D-penicillamine, there was no statistically significant difference among the 3 groups in duration of morning stiffness, walking time, physician's assessment, number of swollen joints, or scores for tender and swollen joints. The slight increase in efficacy of higher dose D-penicillamine was associated with increased toxicity. In order to evaluate clinical efficacy of D-penicillamine (DP) a double-blind study was conducted by the Metalcaptase Research Group consisting of forty-one rheumatological centers in Japan. A total of 179 patients with rheumatoid arthritis (RA) was divided into two groups; one treated with 5 mg (control group) and the other with 100 mg (drug group) of DP in capsule form. The trial lasted 24 weeks. Global judgment by physicians revealed that improvement was found in 27% in the controls and 65% in the drug group. Adverse reactions occurred in 34% of the controls and 49% of the drug group. Skin rashes, taste disturbances, gastrointestinal upset and proteinuria were frequent in the drug group, but severe or fatal reactions could not be seen in this trial.
D-penicillamine appears to have a clinically and statistically significant benefit on the disease activity of patients with rheumatoid arthritis. Its efficacy appears to be similar to that of other disease modifying anti-rheumatic drugs (DMARDs), but with a significantly higher toxicity. Its effects on long-term functional status and radiological progression are not clear from this review.