The Truth About JIA Medications and Cancer Risk 

By Timothy Gower

It’s reassuring to know that there are several effective treatments to manage disease activity and relieve symptoms of juvenile idiopathic arthritis (JIA). But for many parents, that comfort is offset by concern, since some reports have linked the most effective medications to an increased risk for cancer. However, while kids with JIA do have modestly increased odds for developing malignant tumors, growing research suggests that medicines used to manage the disease aren’t to blame. The real culprit is more likely uncontrolled inflammation, which not only makes joints ache, but may also increase cancer risk. 

Reports and Reality

Some research has linked the conventional DMARD, methotrexate—a common treatment for JIA, ankylosing spondylitis, lupus, rheumatoid arthritis (RA) and other forms of inflammatory arthritis—to lymphoma, a cancer that arises in immune cells called lymphocytes. The risk appears to be greatest in patients who also have the Epstein-Barr virus [a common virus that causes infectious mononucleosis or “mono”], says Eric Matteson, MD, a rheumatologist at the Mayo Clinic, in Rochester, Minnesota.

Over the last generation, many patients with inflammatory arthritis have benefited from a powerful class of medications called tumor necrosis factor (TNF) inhibitors (i.e., etanercept, adalimumab, infliximab). These drugs, which belong to the biologic class of DMARDs, work by blocking the activity of a key protein that causes inflammation. However, shortly after TNF inhibitors were introduced, the Food and Drug Administration (FDA) began receiving reports that a small number of children and teens treated with the drugs had developed cancer, especially lymphoma. In 2009, the FDA announced that it would require manufacturers of TNF inhibitors to warn doctors about the association between these drugs and cancer. 

But while that may sound alarming, there is far more to the story, explains Timothy Beukelman, MD, an associate professor in the Division of Pediatric Rheumatology at the University of Alabama at Birmingham School of Medicine. For starters, the FDA lacked reliable data on how many kids in the United States were taking TNF inhibitors. So, it’s hard to know whether the number who developed cancer was unusually high compared to other children who weren’t taking TNF inhibitors, he says.

The FDA also didn’t collect any data on what drugs besides TNF inhibitors had been used by the children who developed cancer, so it’s unknown whether some other medication could have caused malignancies, says Dr. Beukelman. Additionally, many of the cancers reported to the FDA occurred in children who received TNF inhibitors as a treatment for inflammatory bowel disease (IBD). Children with IBD may also be treated with a class of drugs called thiopurines, which are known to cause lymphoma in adults, he says. 

Finally, simply having any form of inflammatory arthritis may increase the risk for lymphoma and other cancers. Lymphomas may be more common in inflammatory arthritis because immune cells are chronically stimulated, which makes them more likely to turn malignant, says Dr. Matteson. It’s no coincidence then, that people with poorly controlled inflammation also have the highest risk for developing lymphoma, he says.

Likewise, another important role of the immune system is to detect and destroy cancer cells. But because people with JIA and other autoimmune diseases have impaired immune systems, they are likely more vulnerable to cancer, says Dr. Beukelman. 

Shedding Light on Safety Concerns

With lingering questions about the safety of TNF inhibitors in mind, Dr. Beukelman and several colleagues decided to study the connection between these drugs, JIA and cancer. Using national databases, they identified nearly 28,000 children with JIA and divided them into two groups: patients who received TNF inhibitors and those who didn’t. By counting cancer cases in each group, they found that the likelihood of developing a malignancy was similar in both. “That means that TNF inhibitors didn’t appear to increase a patient’s background risk of cancer,” says Dr. Beukelman. The research strongly suggests that the benefits of reducing inflammation with medication far outweigh the risks.

Dr. Beukelman’s study determined that kids with JIA are two to three times more likely to develop cancer than children who don’t have inflammatory arthritis. But it’s important to keep that increased risk in perspective: Childhood cancer is very rare to begin with – just one or two kids out of every 10,000 in the United States develop malignancies. In other words, kids with inflammatory arthritis have about a two to six in 10,000 chance of getting cancer. 

However, studies in adult RA patients suggest that methotrexate and TNF inhibitors may modestly increase the risk for skin cancer. If your child is taking either of these drugs, play it safe and make sure they always wear sun block outdoors.