An inflammatory disease of the immune system, rheumatoid arthritis (RA) is associated with increased occurrence of lymphoma--or cancers of the lymphatic system, which plays an integral role in the body's ability to fight infection. While various studies have affirmed this link, none have been able to pinpoint the specific effects of disease activity on lymphoma risk, let alone distinguish them from the effects of disease treatment.
Are certain RA patients more vulnerable to developing lymphoma? Do certain RA therapies--from standard NSAIDs (nonsteroidal anti-inflammatory drugs) and DMARDs (disease-modifying antirheumatic drugs) to novel immunosuppressive agents like TNF (tumor necrosis factor) blockers--work to alleviate or aggravate lymphoma risk? On a quest for answers, researchers in Sweden conducted the largest investigation of the link between RA and lymphoma to date. Their findings, featured in the March 2006 issue of Arthritis & Rheumatism, indicate a substantially increased risk of lymphoma among patients with severe RA. Very high and prolonged inflammatory activity, not its treatment, is the major risk factor.
Drawing their sample from a national register of nearly 75,000 RA patients, the research team analyzed the medical records and case histories of 378 RA patients afflicted with malignant lymphoma between 1964 and 1995 and 378 individually matched, lymphoma-free controls. Using statistical analysis, the relative risks or odds ratios for lymphoma were assessed for three different levels of overall disease activity--low, medium, or high--based on disease duration and swollen and tender joint counts. Odds ratios for lymphoma were also compared to treatment in broad categories: any DMARD, any NSAID, aspirin, oral steroids, injected steroids, and cytotoxic drugs. No patient in the sample had received anti-TNF therapy. In addition, lymphoma specimens were reclassified and tested for Epstein-Barr virus (EBV).
Compared with low RA activity, medium RA activity was associated with an 8-fold increase in the risk for lymphoma. The odds ratio rose dramatically for high RA activity--to a 70-fold increase in lymphoma risk. The researchers also observed increased risks of lymphoma associated with pronounced, irreversible joint damage in the hands, feet, and knees documented in the last year before lymphoma diagnosis.