Rheumatoid Arthritis and Cancer Risk

Learn the link between cancer and the drugs used to treat RA.

By Timothy Gower

People with rheumatoid arthritis (RA), and some related inflammatory diseases, face the reality of a slightly increased risk for developing certain types of cancer. Over the years, some researchers have questioned whether commonly used inflammation-fighting medications – particularly biologics – might take some of the blame for a heightened cancer threat. However, growing evidence tells us that chronic inflammation is the primary link between RA and cancer.

Lymphoma and RA

A number of studies show that people with RA have roughly double the average risk for developing lymphoma, a group of cancers that arise in the blood. This is likely caused by chronic inflammatory stimulation of the immune system. Two key producers of inflammation, lymphocytes called B cells and T cells, are the same cells that become cancerous in lymphomas. The increased activity of these lymphocytes in RA makes them more likely to turn malignant. As evidence, doctors note that people with poorly controlled inflammation have the highest risk for developing lymphoma.

Understanding Lymphoma Risk

Although this connection may concern you, it’s important to bear in mind that lymphomas are relatively rare. One of the most common forms, non-Hodgkin lymphoma, occurs in about one in 50 adults in the United States (2%) – which means that your risk as a person with RA grows to about two in 50 (4%). Hodgkin lymphoma is even more rare, affecting fewer than three people out of every 100,000. (For comparison, one in eight women develops breast cancer, and a similar portion of men are diagnosed with prostate cancer.) In other words, the increased threat of lymphoma in RA is real, but modest.

Do RA Drugs Add to the Risk?

Medications that affect the immune system have the potential to increase cancer risk. This appears to be the case with a few drugs that are infrequently used to treat RA, such as cyclophosphamide and azathioprine. However, one of the most widely used RA medications, methotrexate, has been linked to lymphoma as well. RA patients who take methotrexate are more likely to develop lymphoma if they also have the Epstein-Barr virus.

Early Biologics Studies and Cancer Risk

The association between biologic drugs and cancer used to be more controversial than it is now. By suppressing specific components of the immune system, it seemed plausible that biologics might increase cancer risk. But while that possibility stoked concerns about the safety of biologics when they were introduced in the 1990s, more recent news disputes that notion.

Early on, studies suggested that biologic users might have up to a three-fold increased risk for developing cancer, particularly lymphomas. However, more recent research appears to clear the medications. A 2016 study published in Annals of Rheumatic Diseases involving more than 15,000 RA patients who took a biologic found no increased risk for lymphoma.

How the View of Risks Changed

What happened? Early studies of biologics primarily included patients with long-standing, severe RA. Because of their persistent inflammation, those patients were at the highest risk for lymphoma. This distorted the apparent risk of biologics. Now that doctors are giving the medications to more mildly affected patients, the association is being lost.

Until recently, doctors were reluctant to prescribe most biologics to RA patients who had cancer, either currently or in the past, out of concern that the drugs might awaken a dormant tumor or worsen an existing malignancy. But given the lack of evidence for any link between biologics and lymphoma, or any other form of cancer, doctors are backing away from that.

Other Cancer Risks

Lung Cancer:  People with RA have an increased risk for lung cancer. Smoking tobacco is the obvious link between the two diseases, since the habit dramatically raises the risk for both. But research indicates that RA patients who smoke are about 40% more likely to develop lung cancer than smokers who don’t have RA, suggesting that chronic inflammation plays a role as well.

Skin Cancer: Both methotrexate and biologic drugs seem to slightly increase the risk for two forms of skin cancer, known as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). According to a 2016 study in the BMJ, taking a biologic raises the risk for SCC by 30%, though that’s still a relatively small concern: Treating 1,600 patients with biologics for a year would lead to just one additional case of SCC than would otherwise be expected. Both BCC and SCC are highly treatable; but if you take a biologic, wear sun block and report any moles or other skin irregularities to your doctor.

The Bottom Line

An increased risk for a serious disease, even if it’s small, needs to be considered when deciding to take any medication. But it’s important to remember that poorly controlled RA not only damages joints, but also raises the risk for heart disease and other threats. For many, the benefits of controlling rheumatoid arthritis far outweigh the risks of cancer.

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