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WASHINGTON -- The use of tumor necrosis factor (TNF) inhibitors in children with juvenile idiopathic arthritis (JIA) did not appear to raise the risk of malignancy, a researcher reported here.

Children with JIA are already at increased risk for malignancy, possibly through the effects of chronic inflammation, similar to what was seen among adults with rheumatoid arthritis in the prebiologic era. In 2009, as a result of spontaneous voluntary adverse event reporting, the U.S. FDA issued a so-called boxed warning about lymphoma and other malignancies in children with JIA.

"There was then, and still remains now, much uncertainty about the possible causes of the association between TNF inhibitors and malignancy in children with JIA, particularly because most children with JIA treated with TNF inhibitors have previously been treated with other medications such as methotrexate that may carry increased risks of malignancy," said , of the University of Alabama at Birmingham, in a press conference at the American College of Rheumatology annual meeting.

Subsequent to the FDA warning, several large retrospective studies have examined rates of malignancy in children with JIA. Four of the five published studies to date have suggested a two- to three-fold increase in malignancy in the absence of TNF inhibitor treatment, but there have not been any published studies of sufficient sample size to adequately examine the association of TNF inhibitors and malignancy in children with JIA.

To address this knowledge gap, Beukelman's group used administrative claims data from Medicaid for the years 2000 to 2010, and commercial insurance claims from 2010 to 2014, to determine relative rates of malignancy in children with JIA treated with TNF inhibitors, comparing them with rates in children in the general population, and also with rates in children with JIA not treated with TNF inhibitors.

Diagnosis codes and pharmacy records in claims data were used to determine medication use, and cases of malignancy were based on diagnosis codes with additional evidence of treatment. Cases of malignancies were compared with the number expected in the general population, matching for age, sex, and race, using data from the National Cancer Institute's database.

In the JIA population they observed 20 incident malignancies among approximately 27,000 children and seven among those following anti-TNF exposure, who numbered approximately 3,300.

"Compared with the general population, the incidence rate of malignancy for all children with JIA was increased with a standardized incidence ratio of 2.4 and a confidence interval that excluded no difference," Beukelman said.

The standardized incidence ratio (SIR) of children with JIA who did not receive treatment with methotrexate, TNF inhibition, or other systemic immunosuppressive medications was the same as that for all patients with JIA, again at 2.4 and with a 95% CI that excluded no difference.

And the SIR following the use of TNF inhibitors was similar, at 2.9, again with a 95% CI that excluded no difference.

Then, when children who were TNF inhibitor users were compared with all children with JIA, the result was an SIR of 1.2, but with a 95% CI that included, rather than excluded, no difference. When compared with the JIA population with no medication use, the result was the same.

"Thus, the rate of malignancy with JIA who received TNF inhibitors appears similar to the rate in children with JIA who did not receive anti-TNF treatment," Beukelman said.

"In conclusion, our study confirms that children diagnosed with JIA have an increased rate of malignancy regardless of treatment, and also suggests that TNF inhibitors are not associated with a significant risk of malignancy," he said.

"The study is not 100% definitive, but it appears that there's not a greatly increased risk in JIA with anti-TNF treatment," Beukelman told 番茄社区app. "Unfortunately, concerns about malignancy among parents and physicians have led in some instances to decreased use of these agents when clinically appropriate, with unfortunate long-term results."

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