Juvenile Arthritis and Cancer Risk, What Parents Should Know

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For the parents of the estimated 300,000 children with juvenile idiopathic arthritis (JIA), the results of the new study from the University of Alabama at Birmingham are sobering. The study’s authors found that children with juvenile arthritis had a greater cancer risk than children without arthritis.

What did the study show about cancer risk

The study involved 7,812 children with JIA and compared them with 321,821 children without juvenile arthritis but with another chronic disease such as asthma or ADHD. Investigators followed the participants for about 18 months.

Data on all the participants were evaluated, and the conclusion reached by Dr. Timothy Beukelman, the study’s lead author and an associate professor of pediatrics at UAB, and his team was that the children with arthritis developed 4.4 times as many new growths classified as probable or highly probable malignancies (cancerous).

Among the first questions on the minds of parents of children with juvenile arthritis is “why?” What is the reason for this increased risk of cancer in their children?

One natural place to turn to look for answers is the treatment for juvenile idiopathic arthritis, which includes drugs in a class called tumor necrosis factor (TNF) inhibitors. “Natural” because since the introduction of these drugs in the late 1990s, there has been much concern and discussion about an increased risk of malignancy associated with their use.

In the current UAB study, 1,484 of the 7,812 children with juvenile idiopathic arthritis received treatment with TNF inhibitors. The researchers reported they found no malignancies in the children with juvenile arthritis who were treated with the medications.

Although Beukelman noted there was no association between the use of TNF inhibitors and the risk of cancer in this study, it’s important to note that the Food and Drug Administration (FDA) required a black box warning to be added to TNF inhibitors in 2009 because of reported cases of an increased risk of cancer in children who took the drugs.

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Drugs for juvenile arthritis and cancer risk
In the news release from the FDA on August 4, 2009, it stated that the warning “highlight[s] the increased risk of cancer in children and adolescents who receive these drugs to treat juvenile rheumatoid arthritis, the inflammatory bowel disorder, Crohn’s disease, and other inflammatory diseases.”

This boxed warning was the second for the TNF inhibitors: the first was issued in September 2008 and concerned an increased risk of serious fungal infections. TNF inhibitors include adalimumab (Humira), certolizumab) Cimzia), etancercept (Enbrel), golimumab (Simponi), and infliximab (Remicade).

The TNF inhibitors work by blocking and neutralizing a protein called tumor necrosis factor-alpha. When this protein is overproduced, as it is in juvenile rheumatoid arthritis and other chronic inflammatory disease, it causes inflammation and damage to tissue, cartilage, and bones.

According to the FDA’s announcement, an evaluation of reports of cancer and adolescents in the United States who had been treated with TNF inhibitors revealed an increased risk of cancer after an average treatment period of 30 months. About 50 percent of the cancers were lymphomas, and some of the cancers were fatal.

What is the reason for the increased cancer risk?
According to Beukelman, however, the decision by the FDA to order the black box warning was “based on data comparing cancer rates in children who received TNF inhibitors compared to children in the general population,” and did not take into account the use of other arthritis drugs such as methotrexate or even the possibility that juvenile idiopathic arthritis itself may have some cancer-causing effects.

Regarding the new findings, he said “It appears clear that there is an increased risk of malignancy in children with JIA, but it’s not all attributable to TNF inhibitors.” He stressed that at least some of the increased cancer risk, “and perhaps even all of it,” could be related to the disease process itself or to the use of other drug treatments for JIA.

The findings of this new study raise important concerns and questions for parents of children who have juvenile idiopathic arthritis. Although the study does not provide answers, it does offer parents information they should know when they approach their physicians to discuss the possible reasons for the increased cancer risk associated with juvenile arthritis and what course of action they should take to best serve their children.

SOURCES:
Beukelman T, Haynes K, Curtis JR, Xie F, Chen L, Bemrich-Stolz CJ, Delzell E, Saag KG, Solomon DH, Lewis JD. Rates of malignancy associated with juvenile idiopathic arthritis and its treatment. Arthritis & Rheumatism 2012; DOI: 10.1002/art.34348
Food and Drug Administration
University of Alabama, Birmingham

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