Severe Rheumatoid Arthritis Linked to Lymphoma Risk

By Jeff Minerd, MedPage Today Staff Writer
Reviewed by Robert Jasmer, MD; Assistant Professor of Medicine, University of California, San Francisco
February 27, 2006

UPPSALA, Sweden, Feb. 27 - Severe and longstanding rheumatoid arthritis leads to 70 times the risk for developing lymphoma compared with patients having mild disease, according to researchers here.

Aggressive treatment of RA may reduce these patients' risk of lymphoma by reducing cumulative inflammation, reported Eva Baecklund, M.D., of the Akademiska Hospital and colleagues here in a study published in the March issue of Arthritis & Rheumatism.

The good news is that standard disease-modifying, anti-rheumatic drug (DMARD) treatment was not associated with increased lymphoma risk, the researchers said.

Drawing from a national register of nearly 75,000 Swedish RA patients, the study focused on 378 of them who were diagnosed with malignant lymphoma between 1964 and 1995. Using 378 individually matched RA patients who were free of lymphoma, the researchers calculated odds ratios for lymphoma associated with low, medium, and high RA disease activity.

Compared with patients with low disease activity, those with medium disease activity had a more than sevenfold increase in lymphoma risk (odds ratio=7.7; 95% confidence interval=4.8-12.3), and those with high disease activity had a 71-fold risk increase (OR=71.3; 95% CI=24.1-211.4).

Fifty-two percent of RA patients with lymphoma were categorized with medium disease, and 23% of RA patients were classified as having high disease activity, based on duration of symptoms and swollen and tender joint counts.

The researchers also looked for an association between lymphoma risk and RA treatment, including methotrexate, anti-malarial agents, oral steroids, non-steroidal anti-inflammatory drugs, and aspirin. But no link association was found.

Only the drug azathioprine (Imuran, Azasan) was associated with significantly increased lymphoma risk (OR=4.3; 95% CI=1.6-12.0), but this drug is not regarded as a traditional DMARD and is rarely used in current RA treatment, the investigators said.

The chronic inflammation and stimulation of the immune system in RA likely leads to cancer through as-yet unspecified pathways, the researchers speculated.

"The association between lymphoma risk and very high and/or longstanding disease activity indicates that most patients with RA will never have any clinically relevant increased lymphoma risk," the authors said. "In contrast, those who do may have highly increased risks, but can be readily identified based on their accrued inflammatory burden."

They added, "Conventional medical treatment to suppress and alleviate disease activity is not by itself a risk factor for lymphoma. Rather, it is possible that aggressive treatment may reduce lymphoma risk by reducing cumulative inflammation."

Primary source: Arthritis & Rheumatism
Source reference: Baecklund E et al. Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis & Rheumatism. 2006; 54(3):692-701.

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