Clinical Trial of Penicillamine in Rheumatoid Arthritis

Abstract

The medical records of our first 200 consecutive rheumatoid arthritis patients treated with penicillamine were analyzed retrospectively. All but 5 patients (97.5%) had undergone earlier chrysotherapy that resulted in either therapeutic failure or toxicity. Only 57 patients (28.5 %) were still receiving penicillamine on January I, 1981, and the duration of therapy ranged from 23 to 62 months. The dropout rate due to toxicity, therapeutic failure, relapse, or other reasons was very high (71.5%). Toxic effects required permanent discontinuance in 56 patients (28%). Therapy was discontinued for 36 patients (18%) because of no benefit. A striking number (20) had relapse after therapeutic success and while continuing to take penicillamine, and the therapy had to be discontinued, a relapse rate of 10%. Therapy for the remaining 15.5% was discontinued for miscellaneous reasons that were not related to penicillamine per se: patient anxiety (6%), lost to followup (5%), hospitalization for reasons unrelated to penicillamine therapy (2%), lack of cooperation and study protocol (1% each), or pregnancy (0.5%). By our criteria, 142Norman 0. Rothermich, MD: Clinical Professor of Medicine,

Effects of D-penicillamine on growth and cell cycle kinetics of cultured rabbit articular chondrocytes.

“…D-penicillamine, a drug used for the treatment of Wilson's disease,' heavy-metal poisoning,2 and cys-tinuria3 has been shown to have a beneficial effect on the course of rheumatoid arthritis. 4 The thiol group is responsible for the interaction with disulphide bridges and with thiol groups in biological systems, while both the amino and thiol groups are involved in the interaction with aldehydes and chelation of heavy metals.5 These properties account for some of the effects observed during D-penicillamine treatment of rheumatoid arthritis-for example, a diminution of rheumatoid factor and of circulating immune com-plexes6`-but the mechanism underlying its therapeutic efficacy in this disease still remains obscure. D-penicillamine has also been shown to affect macrophage functions9 and lymphocyte proliferation.10 It reduces the proliferation of fibroblasts and rheumatoid synovial cells in culture.1" Its action on articular chondrocytes, a cell type particularly implicated in rheumatoid disease, had not been investigated.…”

Does second-line therapy affect the radiological progression of rheumatoid arthritis?

“…(2) The final scores over the 4 showed in their study of intramuscular gold in early disease, greater radiological deterioration in their group on low-dose gold (total < 500 mg) than in their group on high-dose gold (total 500 mg or more). Unfortunately these groups were not comparable with respect to numbers of erosions at the start of the study.…”

“…In addition these drugs are known to improve laboratory indices of inflammation such as erythrocyte sedimentation rate (ESR) and haemoglobin. [1][2][3][4][5][6] Few studies have been published, however, on the effect of second-line drugs on the radiological progression of the disease, and even among the reported studies there is a degree of disagreement.3 [6][7][8] Carrying out such a study is fraught with difficulties, particularly in maintaining a control group over the necessary long follow-up period. Some would consider such a control group ethically unjustified; in addition we have found it impracticable to maintain these patients off second-line drugs.…”

Therapeutic Progress—review Vitreatment of Rheumatoid Arthritis

“…Two reports by Rothermich et ul. (70,71) suggest that they cannot. In a follow-up study of patients given gold, after 5 years only 20 of 97 patients with RA were still taking the drug; full remission had occurred in only two cases, the others had had gold withdrawn due to either toxicity or lack of effect.…”