mitopodozide and Arthritis--Rheumatoid

Twenty-two patients with amyloidosis secondary to rheumatoid arthritis were randomised and followed prospectively in order to determine whether treatment with cytotoxic drugs could postpone the development of end-stage renal failure. The diagnosis of amyloidosis was based on albuminuria, amyloid-positive rectal and/or abdominal fat aspiration and/or renal biopsies. Renal function was followed by repeated 51Cr-EDTA measurements of the glomerular filtration rate (GFR). Urinary albumin and serum-creatinine were found unreliable as predictors of renal function. GFR declined more rapidly in the patient group receiving only symptomatic drugs and no cytotoxic drugs (NT-group). After an initial decline, the GFR in the cytotoxic drug treatment group (T-group), mean treatment quotient 79%, levelled off and remained constant for a considerable time. The mean observation time was 45.7 months in the NT-group and 53.5 months in the T-group. Seven out of eleven patients in the NT-group developed end-stage renal disease, compared to two out of eleven patients in the T-group. The cumulative proportion of survivors in the NT-group at 36 and 60 months was 71% and 27% respectively. The corresponding figures in the T-group were 89% and 89%. The difference in favour of the cytotoxic drug-treated group was significant (p less than 0.04).

Topics: Adult; Aged; Amyloidosis; Arthritis, Rheumatoid; Azathioprine; Chlorambucil; Cyclophosphamide; Female; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Male; Middle Aged; Podophyllin; Podophyllotoxin; Prospective Studies; Random Allocation

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.

Topics: Antineoplastic Agents; Arthritis, Rheumatoid; Cohort Studies; Female; Gold Sodium Thiomalate; Humans; Infusions, Parenteral; Male; Morbidity; Neoplasms; Podophyllin; Podophyllotoxin; Risk Factors; Sweden

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.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Cohort Studies; Female; Gold; Humans; Incidence; Injections; Life Tables; Male; Middle Aged; Neoplasms; Patient Compliance; Patient Dropouts; Podophyllin; Podophyllotoxin; Prognosis; Risk Factors; Treatment Outcome

Topics: Arthritis, Rheumatoid; Humans; Podophyllin; Podophyllotoxin

Topics: Arthritis, Rheumatoid; Humans; Podophyllin; Podophyllotoxin

Drug withdrawal rate and reasons for treatment termination were studied in a retrospective life-table analysis of patients with rheumatoid arthritis prescribed Proresid, a semisynthetic podophyllotoxin derivative. Two years after starting with Proresid medication, half of the patients were still on treatment. After 5 years the termination rate had risen to 71%. Gastrointestinal side effects were the most common reason for abandoning medication. The results are compared with those found in other studies of similar desing. It is concluded that Proresid is a valuable and well-tolerated disease-modifying drug for long-term treatment of rheumatoid Arthritis.

Topics: Actuarial Analysis; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Arthritis, Rheumatoid; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Middle Aged; Podophyllin; Podophyllotoxin; Retrospective Studies

A severe haemolytic transfusion reaction due to anti-Jka, is described. The antibody was not detected in the cross-match test in saline and 22% bovine serum albumin after incubation at 4, 20 and 37 degrees C. This observation shows that the indirect antiglobulin test (= indirect Coombs reaction), which is able to reveal such antibodies, should be routinely performed in all cases with a history of transfusion and/or pregnancy.

Topics: Acute Kidney Injury; Adult; Anemia; Arthritis, Rheumatoid; Blood Group Antigens; Coombs Test; Cyclophosphamide; Erythrocytes; Female; Humans; Isoantibodies; Kidd Blood-Group System; Podophyllin; Podophyllotoxin; Transfusion Reaction

Patients with rheumatoid arthritis were treated with podophyllotoxin derivatives (PTD) or with cyclophosphamide. Increased concentrations of C1r-C1s-C1 inactivator complexes (C1r-C1s-C1 IA) in serum provided evidence for C1 activation, which was most pronounced before treatment. During treatment the levels of C1r-C1s-C1 IA clearly decreased, while the levels of C4 increased. This rise in C4 was contrasted to the decrease in other acute phase reactants as C-reactive protein. Circulating immune complexes were assessed by the C1q deviation test (C1q DV) and the C1 binding assay (C1q BA). Discrepancies were noted in the outcome of the two assays. Of parameters reflecting C1 inactivation C1r-C1s-C1 IA complexes were positively and C4 negatively correlated with the inflammatory activity as measured by synovitis index (SI). The values in C1q DV correlated with the C1r-C1s-C1 IA values and with SI. In contrast, C1q BA correlated with CRP but not with C1r-C1s-C1 IA or SI. The study gave evidence for a relationship between C1 activation as detected in serum and the extent of synovial inflammation in RA. The possibility is discussed that substances other than immune complexes may be involved in C1 activation and contribute to the synovial inflammation.

Topics: Adult; Aged; Arthritis, Rheumatoid; Complement Activation; Complement C1; Cyclophosphamide; Female; Humans; Hydrazines; Male; Middle Aged; Podophyllin; Podophyllotoxin; Synovitis