Auranofin and D-penicillamine: a one year comparative study of safety and efficacy in patients with rheumatoid arthritis followed by a two year open assessment of auranofin
Forty-six patients with classical or definite rheumatoid arthritis participated in a prospective clinical trial comparing auranofin 6 mg/day (26 patients) with D-penicillamine 500 mg/day (20 patients) during one year. NSAIDs were also given throughout the study period. After the first year, patients receiving auranofin with a satisfactory response continued for a further two years with a reduced dose of 3 mg/day. However the 6 mg dose could be reinstituted in patients showing deterioration after dose reduction. This paper only discusses the long-term treatment with auranofin. Seven out of 26 patients did not complete the one year treatment period; three because they did not return to follow-up, one because of inefficacy, and 3 because of untoward events. During the second year 5 more patients discontinued treatment, one because he was lost to follow-up, two because of inefficacy, one because of untoward events and another one because of a surgical procedure of the left knee. Two more patients discontinued auranofin treatment during the third year, one because of a flare up of his disease activity, and one because of a rash. Statistically significant improvements in the number of tender joints, activity and articular indices, duration of morning stiffness, pain score and ESR were observed at each time analysed. Statistically significant reductions in the number of swollen joints were seen throughout the first two years of treatment. Increases in grip strength were statistically significant at 6, 24 and 30 months. A statistically significant reduction was seen after 6 months of treatment in serum IgA and IgM concentrations. A clinically significant improvement was already observed after 3 months of treatment but most patients showed greatest improvement between the beginning of the trial and 12 months, thereafter there was little further improvement. Serum gold concentrations showed an early plateauing with no indication of accumulation in the intravascular compartment. No gold could be found in serum obtained in 6 patients, 2 to 6 months after treatment with auranofin was discontinued. No correlation could be demonstrated between serum gold levels un-toward events and clinical response. Changes in bowel habits or diarrhoea were reported by 19% of the patients, but in only one case diarrhoea associated with rash and stomatitis was severe enough to warrant withdrawal of treatment. Mucocutaneous reactions were noted in 8% of the patients. In two patients the symptoms, in one case associated with severe diarrhoea, necessitated withdrawal. Treatment was discontinued on account of increased anti-DNA antibody titre in one patient, leucopenia in another patient and dyspnoea and myalgia in another one. These results indicate that auranofin reduces in a significant way the activity of rheumatoid arthritis. The data also suggest that the beneficial effect obtained with auranofin at a dose of 6 mg/day during the first year could not be maintained by 3 mg/day, since in all the patients the 6 mg dose was reinstituted for a certain period because of deterioration after dose reduction.