Incidence of neoplasms in patients with rheumatoid arthritis exposed to different treatment regimens.

Immunosuppressive drugs have been used during the last 30 years in treatment of patients with severe rheumatoid arthritis. The drugs commonly used are cyclophosphamide and chlorambucil (alkylating agents), azathioprine (purine analogue), and methotrexate (folic acid analogue). There is evidence that all four immunosuppressive drugs can reduce synovitis, but disease activity almost always recurs after therapy is stopped. Since adverse reactions are frequent, less than 50 percent of patients are able to continue a particular drug for more than one year. Since it takes three to 12 months to achieve maximal effects, those patients who are unable to continue the drug receive little benefit from it. Patients treated with alkylating agents have an increased risk of development of acute nonlymphocytic leukemia, and both alkylating agents and azathioprine are associated with the development of non-Hodgkin's lymphoma. Cyclophosphamide therapy increases the risk of carcinoma of the bladder. There have been several long-term studies of patients with rheumatoid arthritis treated with azathioprine and cyclophosphamide and the incidence of most of the common cancers is not increased. Data on the possible increased risk of malignancy in rheumatoid arthritis are still being collected, and until further information is available, the use of immunosuppressive drugs, particularly alkylating agents, in the treatment of rheumatoid arthritis should be reserved for patients with severe progressive disease or life-threatening complications.