The incidence of cancer associated with the treatment of rheumatoid arthritis

Semin Arthritis Rheum. 1999 Dec;29(3):148-58. doi: 10.1016/s0049-0172(99)80026-2.


Objectives: The treatment of rheumatoid arthritis (RA) targets inflammation either by inhibiting the activation of immune cells or their clonal expansion. We evaluated the available evidence concerning the risk of cancer associated with RA treatment.

Method: Articles published between 1966 and 1998 reporting the incidence of cancer in RA patients were reviewed.

Results: Large follow-up studies suggest the relative risk (RR) of lymphomas associated with RA is about twofold higher than in the general population. A role for azathioprine in the development of lymphomas and a role for cyclophosphamide in cancers, particularly bladder cancer, has been suggested. However, no studies have shown that methotrexate increases the risk of cancer in RA patients. Studies that showed an increased risk of cancer associated with gold or cyclosporine therapy in RA patients are inconclusive as they have used cancer incidence in the general population as the reference. One study measured the RR of cancer in a group of cyclosporine-treated RA patients (1.6 year on average) using RA patients as a control and found no enhanced risk.

Conclusions: Although evidence suggests an increased risk of specific cancers associated with the use of some treatments, this may be outweighed by the potential benefit of therapy, especially in patients with severe disease.

Publication types

  • Comparative Study

MeSH terms

  • Antirheumatic Agents / adverse effects*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / epidemiology
  • Arthritis, Rheumatoid / immunology
  • Autoimmunity / drug effects
  • Global Health
  • Humans
  • Immunosuppression Therapy / adverse effects
  • Incidence
  • Neoplasms / chemically induced*
  • Neoplasms / epidemiology*
  • Neoplasms / immunology
  • Prognosis
  • Prospective Studies
  • Registries / statistics & numerical data
  • Risk Factors
  • Survival Rate


  • Antirheumatic Agents