EFFECTS OF CYCLOPHOSPHAMIDE ON THE DEVELOPMENT OF MALIGNANCY AND ON LONG-TERM SURVIVAL OF PATIENTS WITH RHEUMATOID-ARTHRITIS - A 20-YEAR FOLLOW-UP-STUDY

Objective. To examine the effects of cyclophosphamide (CYC) on the dev elopment of malignancies and on the Long-term survival of patients wit h rheumatoid arthritis (RA), Methods, We used a longitudinal cohort de sign in which 119 patients (76 women and 43 men) with refractory RA wh o were treated with oral CYC between 1968 and 1973 were compared with 119 control patients with RA (matched for age, sex, disease duration, and functional class) who were evaluated during the same time period b ut did not receive CYC. Results. There was increased risk of malignanc y in the CYC-treated group, with 50 cancers found in 37 patients in th e CYC group compared with 26 cancers in 25 of the control patients (P < 0.05), The relative risk of cancer for those treated with CYC was 1. 5 (95% confidence interval 0.93-5.5), Nine of the malignancies in the CYC group were bladder cancers and 19 were skin cancers, compared with no bladder cancers and 6 skin cancers in the control group, The total dose of CYC was higher in those who developed cancer, particularly in those with bladder cancer, Three of the bladder cancers occurred 14, 16, and 17 years after CYC had been discontinued, Conclusion. The risk of malignancy, particularly bladder cancer, in RA patients treated wi th oral CYC continues even 17 years after discontinuation of the drug.