Children with juvenile idiopathic arthritis (JIA), the most common form of childhood arthritis, may be at higher risk of developing cancer than children who do not have the condition, according to a new study published in the journal Arthritis & Rheumatism.
Researchers identified 7,812 children with JIA and compared them with thousands of children not affected by JIA and found that the arthritic children developed about four times as many new growths considered likely to be cancerous as children who did not have arthritis. They followed the children for about 18 months.
"Based on the data, it appears that being diagnosed with JIA increases the likelihood of developing malignancies," said Dr. Timothy Beukelman, the study's lead author and an associate professor of pediatrics at the University of Alabama at Birmingham.
But despite the statistically higher risk, Dr. Sampath Prahalad, associate professor of pediatrics and human genetics at the Emory University School of Medicine, said cancer in children with JIA is rare.
"The risk is very low, and it's more common for children with JIA to not get cancer," he said. The study included only 7,812 children with JIA, and nationwide, there are about 300,000. Prahalad was not involved with the research.
Beukelman said there are a number of possible explanations for the finding, but so far, no one knows why JIA may predispose children to cancer. He stressed, however, that there was no association between cancer risk and any treatments for the condition, including the use of drugs known as tumor necrosis factor (TNF) inhibitors.
TNF inhibitors, including the brand-name drugs Enbrel and Humira, are considered by doctors to be revolutionizing treatments that can sometimes stop rheumatoid arthritis in its tracks.
But there have been a number of case reports linking the use of TNF inhibitors to an increased cancer risk in children, prompting the Food and Drug Administration (FDA) to add a black box warning to these drugs in 2009. A black box warning is the strongest warning used by the FDA and indicates a drug has potentially life-threatening effects.
"The initial concern about TNF inhibitors may have been overstated, since some of the risk likely comes from the disease itself," Beukelman said.
Beukelman explained that when the FDA made its decision to include black box warnings on TNF inhibitors, the only data available compared children with JIA who took these drugs with healthy children.
"When we're evaluating the safety of these drugs, it's important to make comparisons to other children with the disease who didn't get the drugs and not comparisons to children in the general population," he said.
Does Disease Itself Predispose to Cancer?
Previous studies have found a link between elevated cancer risk and certain inflammatory conditions in adults.
"There are studies that show that in adults with rheumatoid arthritis, the more severe the disease, the higher the disease activity, so the more likely the patient is to develop malignancy," Beukelman said.
It could be, he explained, that because diseases like JIA attack the body's own immune system, the body isn't able to mount defenses against invading cancer cells.
Another possibility is that the persistent inflammation characteristic of JIA could lead to cancers, particularly in the blood cells, he said.
Prahalad said the study is both concerning and comforting at the same time.
"It's reassuring that these drugs don't seem to increase cancer risk. Clinically, these drugs really make kids better," he said. "But the study also tells us we need to be careful in monitoring children long-term to see if other studies confirm this so we can treat it early if something happens."
"For many patients with JIA, the risk-benefit analysis is very much in favor of treatment with these drugs. We use them frequently and continue to collect data looking at risk," said Dr. Brent Graham, a pediatric rheumatologist at the Monroe Carell Jr. Children's Hospital at Vanderbilt in Nashville, Tenn.
In an accompanying editorial, Drs. Karen and Kenan Onel of the University of Chicago urged caution in interpreting the study results.
The study included only a small number of children with JIA and also included children with arthritis associated with inflammatory bowel disease, a condition that may carry a higher risk of cancer.
Despite the limitations, they wrote that the research highlights the importance of long-term monitoring of children with JIA. Since the symptoms often resolve, children who no longer suffer from the condition may fall off the radar in terms of cancer risk.
"The absolute risk of late consequences of this diease and its treatment must be determined to help identify populations at special risk so that patients can continue to get the appropriate health care monitoring, even as they themselves become increasingly remote from their childhood illness," they wrote.