rheumatoid arthritis drugs cancer risk

Arthritis and Cancer Risk

Do Inflammatory Arthritis and the Drugs Used to Treat it Put You at Higher Cancer Risk?

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It’s an unfortunate reality of life with rheumatoid arthritis (RA): people with this and some other related inflammatory diseases carry a modestly 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 that heightened cancer threat. However, growing evidence tells us that chronic inflammation – not the drugs that treat it – is the primary link between RA and cancer. 

The Lymphoma Connection

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. “That is likely a consequence of chronic inflammatory stimulation of the immune system in rheumatoid arthritis,” explains Eric Matteson, MD, professor of medicine and rheumatologist at the Mayo Clinic, in Rochester, Minnesota. Two key producers of inflammation, lymphocytes called B cells and T cells, are the same cells that become cancerous in lymphomas, notes Matteson. The increased activity of these lymphocytes in RA makes them more likely to turn malignant, he says. As evidence, Dr. Matteson points out that people with poorly controlled inflammation have the highest risk for developing lymphoma. 

Although this 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, says Dr. Matteson. 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. According to Dr. Matteson, however, RA patients who take methotrexate are more likely to develop lymphoma if they also have the Epstein-Barr virus. 

More controversial has been the association between biologic drugs and cancer. “By suppressing specific components of the immune system, it seems plausible that biologics might increase cancer risk,” says Donald Miller, PhD, professor of pharmacy practice at North Dakota State University in Fargo. But while that possibility stoked concerns about the safety of biologics when they were introduced in the 1990s, Miller says, “The news is good.”

Early on, studies suggested that biologic users may have up to a three-fold increased risk for developing cancer, particularly lymphomas. However, more recent research appears to exonerate 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. 

What happened? Early studies of biologics primarily included patients with long-standing, severe RA, explains Susan Goodman, MD, a rheumatologist at the Hospital for Special Surgery in New York City. “Because of their persistent inflammation, those patients are at the highest risk for lymphoma,” says Dr. Goodman. This distorted the apparent risk of biologics. “But now that we’re giving the medications to more mildly affected patients, that association is being lost,” she says.    

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 we’re backing away from that,” says Dr. Matteson, given the lack of evidence for any link between biologics and lymphoma, or any other form of cancer.  

Other Cancers

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 Matteson’s 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. 

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. 

An increased risk for a serious disease, even if it’s small, needs to be considered when deciding to take any medication. But Dr. Matteson reminds his patients that poorly controlled RA not only damages joints, but raises the risk for heart disease and other threats. “The benefits of controlling rheumatoid arthritis,” he insists, “far outweigh the risks of cancer.” 

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