Adding low-dose cyclosporin A to parenteral gold therapy in rheumatoid arthritis: a double-blind placebo-controlled study.

A double-blind, randomized comparison between parenteral gold therapy (PGT) and cyclosporin A (CyA) vs PGT and placebo during 6 months was performed in 40 RA patients experiencing a decreasing effect of ongoing PGT. Patients' overall assessment of health was the only efficacy variable significantly better in the CyA- and PGT-treated vs the placebo- and PGT-treated group. Higher blood pressure and more signs of renal impairment were found during the 6 months treatment in the former compared with the latter group. Six months after the end of the combination therapy, a higher potassium value in the CyA-treated group was the only difference. In conclusion, no effects additional to those expected with single-drug therapy or additional risks of side-effects of either drug were found when combining low-dose CyA with ongoing PGT in RA patients with long disease duration.

A 10 year follow up of parenteral gold therapy in patients with rheumatoid arthritis.

OBJECTIVES: To study the long term tolerance of parenteral gold and subsequent drug treatment in patients with rheumatoid arthritis, including prediction of outcome and 'survival' of sequential treatments. METHODS: A retrospective cohort study of 376 patients was made, including a detailed screening of 237 patients treated in 1989. Reasons for discontinuing treatment were analysed in life table analyses, which were used to compare patients receiving parenteral gold treatment in 1985 and 1989, and two groups of patients receiving disease modifying antirheumatic drugs after parenteral gold treatment. The causes of discontinuation were followed in sequential treatments. RESULTS: The estimated probability of discontinuation of parenteral gold treatment was 29% after six months and 42%, 55%, 74%, and 92% after 1, 2, 5, and 10 years, respectively. Mucocutaneous side effects were the main cause of discontinuation of parenteral gold treatment during the first three years, while the probability of discontinuation because of inefficacy dominated after four years. Side effects also constituted the main cause of discontinuation of treatments given after parenteral gold treatment during the first three years of follow up. No significant differences were found when comparing the termination rates between the first and the second and subsequent treatments after parenteral gold treatment. The main reasons for discontinuing one treatment could not predict the cause of discontinuation of the next treatment. CONCLUSION: Mucocutaneous side effects dominated initially, while inefficacy was the dominating cause of discontinuation of long term parenteral gold treatment. No serious side effects were registered. The cause of discontinuation of one treatment did not predict the cause of discontinuation of the following drug. Drug 'survival' was the same in both treatments after parenteral gold treatment.

Cancer morbidity in rheumatoid arthritis patients treated with Proresid or parenteral gold.

The cancer risk was studied by comparison of 305 rheumatoid arthritis (RA) patients exposed to Proresid during a mean time of 22 months and 305 RA patients exposed to sodium aurothiomalate during a mean time of 19 months with the regional cancer register. The mean observation time was 6.9 years (2,117 person-years) for the Proresid-treated and 7.5 years (2,293 person-years) for the gold-treated patients. No increased risk of total malignancies was observed for either group. However, looking at separate tumours, an increased risk of lymphoma and leukemia was found although only significant in the gold-treated group. It was not correlated to dosage or duration of either therapy. The increased risk is consistent with earlier reports of an increased risk of hematopoietic malignancies in RA patients. Marginal over and underreporting, particularly of hematopoietic malignancies, were observed, mainly due to clinicians' failure to report and to recall false reports.

Proresid therapy in rheumatoid arthritis. A comparison with injectable gold using life-table analysis.

Proresid, mainly consisting of podophyllotoxin derivatives and two glycosides thereof, has been used as a disease-modifying antirheumatic drug in Sweden since the late 1960s. A life-table analysis of Proresid treatment averaging 41 months (range 4-144) in 79 rheumatoid arthritis patients showed a termination rate of 40, 56, 75 and 85% after 1/2, 1, 2 and 4 years, respectively. Dominant reasons for discontinuing therapy were inefficacy (37%) and gastrointestinal symptoms (35%). The risk of discontinuation of therapy due to inefficacy was constant over time, while the risk due to other causes, including side effects, gradually decreased. A comparison with injectable gold therapy showed, after adjusting for confounding factors, that the total termination incidence was higher (p < 0.05) in the Proresid-treated patients. A comparison with the regional cancer register of 334 patients exposed to Proresid for a mean time of 2.2 years showed no increased cancer risk after a mean observation time of 6.1 years.

Outcome of parenteral gold therapy in RA patients: a comparison between two periods using life-table analysis.

Tolerance and outcome of parenteral gold therapy were compared using life-table analysis and ARA remission criteria between 151 rheumatoid arthritis (RA) patients treated in 1983 and in 210 patients treated in 1985. The total risk of termination of therapy was significantly higher in patients treated in 1983 than those treated in 1985. The most common causes were mucocutaneous reactions (41 and 25% in 1983 and 1985, respectively), unsatisfactory effect (15 and 25%) and practical problems (14 and 26%). The outcome regarding all ARA remission criteria except for fatigue (not systematically registered) was significantly more favourable in patients treated in 1985 than in those treated in 1983.