Rheumatoid arthritis (RA) is a challenge under any circumstances. Now a growing body of evidence suggests that this health challenge may put you at increased risk for certain types of cancer and for a poorer prognosis if you develop a malignancy. The burning questions if you have RA: How great are the cancer risks?What’s behind the increase? How can you protect yourself?
RA and Cancer Risk
The association between RA and cancer is not completely clear. Some studies show an increased risk of cancer in people with RA while others show a decreased risk. But the picture becomes more clear when researchers look at specific cancer types.
Lymphoma.
The strongest evidence of a link appears to be between lymphoma—the most common type of blood cancer— and severe RA. Researchers from Sweden examined data from nearly 75,000 RA patients, 378 of whom had lymphoma. The researchers assessed risk for three different levels of disease activity
(low, moderate, and severe) and found that people with moderate disease activity were eight times more likely to have lymphoma than those who had low disease activity, while those with severe disease activity were 70 times more likely. More support for a connection comes from a review of 21 published studies, including the Swedish study and 13 others that tried to determine whether there was a link between lymphoma and RA. The findings, reported last year in Arthritis Research & Therapy, showed that overall, people with RA were twice as likely as the general population to develop lymphoma, particularly Hodgkin’s lymphoma (one of the most curable types of cancer when detected early).
Lung cancer.
The same review also reported that lung cancer was observed more often in people with RA. Based on data from 12 studies, people with RA were 63% more likely to develop lung cancer than the general population.
Cancer at other sites.
In addition, the authors of the review reported a potentially reduced risk of colorectal cancer among people with RA—possibly due to their increased use of nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors. The researchers also reported a slightly reduced risk of breast cancer.
What’s Behind the Link?
An important question that remains unanswered is whether people with RA are more prone to develop certain cancers than others or if the medications they take could be responsible for the increased risk.
In the Swedish study, more than 70% of people with RA had taken traditional disease-modifying antirheumatic drugs, or DMARDs, such as methotrexate (Rheumatrex, Trexall). However, the only DMARD linked to an increased risk of lymphoma was azathioprine (Imuran)—a treatment that is rarely used today. There was also no link between NSAIDs like aspirin and ibuprofen (Advil and others). One encouraging finding was that people who frequently used corticosteroids for inflamed joints had a lower risk of lymphoma, a result that suggests anti-inflammatory drugs could possibly protect against lymphoma.
No participants in the Swedish study were taking the newer DMARDs, called biologic response modifiers (BRMs). However, in a review of nine clinical trials published in the Journal of the American Medical Association, researchers reported that two BRMs—infliximab (Remicade) and adalimumab (Humira)—were associated with an increased risk of certain malignancies, most notably lymphoma and skin cancer, compared with placebo. (No other drugs in this class were studied). Moreover, those treated with the highest doses of the two BRMs had the greatest chance of developing cancer. A possible explanation: Both Remicade and Humira as well as etanercept (Enbrel) block a protein called tumor necrosis factor (TNF), which plays an important role in controlling tumor growth.
RA and Cancer Deaths
The effect of RA on the risk of cancer death is also murky. Consider the results of these two recent studies. In a British study of 257 people with RA, 371 of their same-sex siblings without RA, and 485 unrelated people with osteoarthritis, those with RA were 40% less likely to die of cancer than participants in the other groups.
Although the researchers noted that NSAIDs, which are used by many people with arthritis, may protect those with RA against cancer, it doesn’t explain why the participants with osteoarthritis didn’t have a lowered cancer risk as well. Another British study reached the opposite conclusion. Investigators followed 2,105 people newly diagnosed with inflammatory polyarthritis (inflammation of several joints at once, which often develops into RA). They found that individuals with inflammatory polyarthritis or RA and cancer had a 40% higher risk of dying over a five-year period than cancer patients without inflammatory arthritis or RA. The study authors theorized that because of their general poor health, people with inflammatory arthritis or RA may not receive aggressive cancer therapy. Undoubtedly, more studies are needed to explain these contradictory results.
Our Advice
Multiple studies show a trend toward a higher risk of certain cancers among people with RA. Although the reasons for these connections are not yet fully understood, evidence suggests that treatment with some anti- TNF agents like Remicade and Humira can increase the risk of lymphoma and skin cancer. Nevertheless, it’s important to note that these findings do not mean you should discontinue using anti-TNF agents. These medications are highly effective for people with RA who no longer respond to traditional DMARD therapy.
To reduce your risk of developing skin cancer or lymphoma while taking an anti-TNF agent, avoid exceeding the recommended dosage (3 mg/kg every eight weeks for Remicade and 40 mg every other week for Humira). Staying within these guidelines should not be problematic since studies show that higher doses are rarely more effective than the recommended dose.
Regardless of the type of RA medication you take, if you are a smoker, one of the best things you can do is to stop smoking. Smoking is a risk factor for lymphoma, and it’s responsible for most cases of lung cancer. If you use an anti-TNF agent, you should also take steps to help reduce your risk of developing skin cancer. Use sunscreen with a sun protection factor (SPF) of 15 or higher whenever you go outside, and avoid being in the sun altogether at mid-day.
Also, wear a hat with a brim to protect your head, neck, ears, and face, and weather permitting, pants or long skirts and long-sleeved shirts made of tightly woven fabrics to protect your torso and limbs. In addition, don’t forget about regular visits to a dermatologist for skin cancer checks. Lastly, know the warning signs of cancer. For lung cancer, the symptoms include a chronic cough, trouble breathing, and constant chest pain; for lymphoma, swollen lymph nodes in the neck, upper chest, armpit, abdomen, or groin; and for skin cancer, new skin growths or changes in an old growth.
Source: Jarrod Franklin; Mark Lunt; Diane Bunn; Deborah Symmons; Alan Silman. Arthritis & Rheumatism. 2007;56(3):790-798
