The risk of malignancies in patients with rheumatoid arthritis (RA) has raised some
concern, particularly with immunosuppressive approaches to disease management. Rheumatoid arthritis (RA) is a chronic autoimmune disease that is also characterized by the presence of inflammation. Because of the immune pathways underlying its pathogenesis and what has generally been an immunosuppressive approach to disease management using traditional disease-modifying antirheumatic drugs (DMARDs), the risk of malignancies among RA patients has been of considerable interest. The characterization of this potential risk has become more relevant with the introduction of a new class of agents, biologic DMARDs. While these drugs act by
directly modifying immunologic pathways involved in the pathogenesis of RA, it has
been of concern that their use may be associated with an increased incidence of
cancer. In order to better understand and interpret studies evaluating the risk
associated with these agents, it is first necessary to determine the magnitude of any
underlying risk of cancer that may already be present in patients with RA compared with
the general populatio.
Compared with the general population, the highest risk of a site-specific
malignancy in patients with RA was observed for lymphoma regardless of lymphoma
type. RA is associated with an overall two-fold increase in lymphoma risk compared with the general population. A higher risk was observed for Hodgkin's lymphoma than for non-Hodgkin's
lymphoma, respectively.
Possible mechanisms for an increased risk of lymphoma in RA patients include the fact that RA results in persistent immunologic stimulation (which may lead to clonal selection and predispose CD5+ B cells to malignant transformation), decreases the number and function of T-suppressor lymphocytes including those directed against the pro-oncogenic Epstein-Barr virus, and decreases natural killer cell activity in the synovial fluid, tissue, blood and lymph.Inflammation is believed to play a key role in the risk of lymphoma; epidemiologic studies have suggested that, among patients with RA, higher inflammatory activity is a major risk determinant of lymphoma.
In addition to lymphoma, lung cancer is also more frequently observed in
patients with RA than in the general population. In contrast, the risk of colon cancer appeared to be somewhat reduced in patients with RA.
The observed association between RA and lung cancer may result from several factors. Cigarette smoking would explain an indirect association between RA and lung
cancer as smoking is an independent risk factor for both conditions. The direct causal
association of RA with lung cancer may be mediated by chronic inflammation and/or
presence of interstitial lung disease. Systemic chronic inflammation has been reported
to be a risk factor for lung cancer.
The explanation for the reduced risk of colon cancer is most likely due to the increased use of nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) selective inhibitors by patients with RA. These medications have consistently been associated with a decreased risk of colon cancer
Tumor necrosis factor (TNF) plays an important role in host defense and tumor growth control. Therefore, anti-TNF antibody therapies may increase the risk of serious infections and malignancies. There is evidence of an increased risk of serious infections and a dose-dependent increased risk of malignancies in patients with rheumatoid arthritis treated with anti-TNF antibody therapy. The formal meta-analysis with pooled sparse adverse events data from randomized controlled trials serves as a tool to assess harmful drug effects.