Link between rheumatoid arthritis and cancer examined

Rheumatoid arthritis is an inflammatory disease of the immune system and is thought to be linked to an increased risk of cancers of the lymphatic system.

The lymphatic system plays an important part in the body's ability to fight infection.

Although various studies have noted this link, none have been able to pinpoint the specific effects of the disease on lymphoma risk, let alone distinguish them from the effects of disease treatment.

In the past it has been unclear whether certain RA patients were more vulnerable to developing lymphoma or whether certain RA therapies, ranging from standard NSAIDs (nonsteroidal anti-inflammatory drugs) and DMARDs (disease-modifying antirheumatic drugs), to the new immunosuppressive agents such as TNF (tumor necrosis factor) blockers,alleviate or aggravate the lymphoma risk.

Researchers in Sweden have conducted the largest investigation of this supposed link to date.

Their findings appear to indicate there is a substantially increased risk of lymphoma among patients with severe RA, who have very high and prolonged inflammatory activity, and not by the treatment used.

Using data 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.

Of all the medical treatments assessed, researchers observed increased lymphoma risk associated only with azathioprine (AZA), which is not regarded as a traditional DMARD for RA and rarely used in current treatment.

Lead author, Dr. Lars Klareskog of Karolinska University Hospital in Stockholm, says the study has substantial clinical implications given the many uncertainties surrounding the link between lymphoma and chronic inflammatory diseases.

Klareskog says since a lymphoma risk is strongly associated with exceptionally severe and longstanding RA activity, aggressive treatment may reduce the risk by reducing inflammation.

The study is published in the March 2006 issue of Arthritis & Rheumatism.