Children with JIA face increase risk of developing cancer

Children with juvenile idiopathic arthritis have a two to threefold increased risk of developing cancer compared to similarly-aged children without JIA, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Atlanta. The same study also reported no cases of cancer in children with JIA who were exposed to anti-TNF therapy.

TNF antagonists, also called biologics or anti-TNF therapy, are a class of drugs that have been used since 1998; overall, they have been given to more than 600,000 people worldwide. These drugs are given by injection and lessen inflammation by interfering with biologic substances that cause or worsen the inflammatory process.

"These findings are likely to mitigate concern that arose in 2009 after a study by the Food and Drug Administration raised the possibility that children treated with anti-TNF therapy had an increased risk of developing malignancy compared to children in the general population," says Timothy Beukelman, MD, MSCE, assistant professor of pediatrics in the Division of Pediatric Rheumatology at the University of Alabama at Birmingham and lead investigator in the study. "This study led the FDA to issue a "black box" warning regarding the risk of pediatric malignancy for all of the anti-TNF agents," he says.

About one child in every 1,000 develops some type of juvenile arthritis. These disorders can affect children at any age, although rarely in the first six months of life. It is estimated that around 300,000 children in the U.S. have been diagnosed with JIA. There are several types of JIA, all involving chronic (long-term) joint inflammation. This inflammation begins before patients reach the age of 16, may involve one or many joints, and can cause other symptoms such as fevers, rash and/or eye inflammation and even cause inflammation of the internal organs.

Dr. Beukelman's research team recently used National Medicaid Administrative Claims data from all 50 U.S. states—collected between 2000 and 2005—to identify 7,321 children with JIA confirmed by both a doctor's diagnosis and based on taking medications used to treat the disease. Among these children, 3,194 were taking methotrexate, a disease-modifying antirheumatic drug, and 1,413 were exposed to TNF antagonists.

The rate of cancer among all children with JIA was approximately 59 per 100,000 person-years (number of patients multiplied by number of years of observation). By comparison, the standardized rates of cancer in two groups of children without JIA were approximately 23 to 27 per 100,000 person years. Researchers identified no malignancies in participants with JIA who had been exposed to anti-TNF therapy, though the number of children treated was relatively small.

"I believe that many people agree that there's increased risk [of malignancy in JIA patients], but it's not all attributable to TNF inhibitors. At least part of the increased risk, and perhaps even all of it, appears to be attributable to the disease itself," says Dr. Beukelman.

There have been few studies investigating the relationship between JIA and cancer. However, efforts to establish the background risk of cancer associated with JIA have increased since the FDA issued its findings that TNF inhibitors are associated with an increased risk of cancer. Efforts are also underway to prospectively collect data on all children who are exposed to TNF inhibitors.

"How disease activity in JIA influences the risk of cancer is not known. We did not have access to that kind of clinical information in this type of administrative database," Dr. Beukelman explains. "TNF inhibitors may possibly be associated with an increased risk of cancer; our study did not have enough patients to definitively answer this question. But based on our findings, the amount of risk that the TNF inhibitors may be responsible for appears to be much smaller than initially suspected."

The American College of Rheumatology is an international professional medical society that represents more than 8,000 rheumatologists and rheumatology health professionals around the world. Its mission is to advance rheumatology. The ACR/ARHP Annual Scientific Meeting is the premier meeting in rheumatology. For more information about the meeting, visit www.rheumatology.org/education. Follow the meeting on twitter by using the official hashtag: #ACR2010.