Increased Risk of Lymphoma in Rheumatoid Arthritis Patients

What Causes the Increased Risk?

An increased risk of lymphoma has been associated with rheumatoid arthritis (RA). Various studies have linked the two conditions but it has never been completely clear whether disease activity or the treatments used to battle rheumatoid arthritis cause the increased risk of lymphoma.

Researchers Seek Answers To Lymphoma Risk For Rheumatoid Arthritis Patients

Lymphoma is cancer of the lymphatic system (lymph nodes, spleen, and other organs of the immune system). The connection between an increased risk of lymphoma in rheumatoid arthritis patients concerns researchers, doctors, and patients. Unanswered questions remain:

  • Are some rheumatoid arthritis patients at greater risk than others for developing lymphoma?
  • Are certain medications or treatments for rheumatoid arthritis responsible for the increased risk of developing lymphoma?
  • If it is caused by treatments is it possible to link the increased risk of lymphoma to a certain class of arthritis drugs?

Researchers In Sweden Conduct Large Study

Researchers in Sweden have conducted the largest study to date in an attempt to find answers to these questions. Researchers obtained the medical records and histories of 378 rheumatoid arthritis patients who developed malignant lymphoma between 1964 and 1995.

The patients were selected from a national register of 75,000 rheumatoid arthritis patients. The 378 rheumatoid arthritis patients who had malignant lymphoma were matched to 378 rheumatoid arthritis patients who served as lymphoma-free controls.

Using statistical analysis the relative risks or odds ratios for lymphoma were assessed for low, medium, or high disease activity associated with rheumatoid arthritis. Disease activity was based on the duration of disease and swollen and tender joint counts. Odds ratios were assessed for the following treatment categories:

No patient in the study had ever been on an anti-TNF drug.

Lymphoma patients in the study were also tested for Epstein-Barr virus.

Lymphoma Study Results

  • Medium rheumatoid arthritis activity correlated with an 8-fold increase in risk of lymphoma compared to low rheumatoid arthritis activity.
  • High rheumatoid arthritis activity was associated with a 70-fold increase in lymphoma risk.
  • Increased risk of lymphoma was associated with severe joint damage in the hands, feet, and knees noted in the medical record of the patient within the last year prior to being diagnosed with lymphoma.
  • Over 70 percent of all patients in the study (lymphoma and lymphoma-free controls) had taken DMARDs, including methotrexate.
  • Study results showed no increased lymphoma risk connected to DMARDs, NSAIDs, aspirin, or steroids.
  • Lymphoma risk was low among patients who received frequent steroid injections into their joints.
  • Of the medical treatments analyzed in the study, only Imuran (azathioprine), which is no longer a commonly used DMARD for rheumatoid arthritis, showed an association with increased lymphoma risk.

Lymphoma Study - Conclusion

Researchers concluded that patients with very severe rheumatoid arthritis who have prolonged, active inflammation are at the highest risk for developing lymphoma. Chronic inflammation and not the anti-inflammatory treatments appear to be connected to lymphoma risk in rheumatoid arthritis patients. Early, aggressive treatment to control inflammation is obviously important.

Was this page helpful?

Article Sources

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial policy to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  • "New insights into the link between rheumatoid arthritis and cancer" EurekAlert; Arthritis & Rheumatism, March 2006