Cancer rates are four time higher in children with juvenile idiopathic arthritis, the most common form of persistent arthritis in children, compared to those without the disease, according to a new study.

Researchers from the University of Alabama at Birmingham examined medical records of 7,812 children with juvenile arthritis between 2000 and 2005, and found that their chances of developing cancer was 4.4 time greater than other kids.

Past research have linked cancer to tumor necrosis factor (TNF) inhibitors, a common treatment for illnesses such as arthritis, Crohn's disease, psoriasis, and refractory asthma among others, but researchers from the latest study discovered that even children who didn’t undergo this TNF treatment were 3.9 times more likely to develop cancer.

TNF inhibitors, which include brand-name drugs like Enbrel, Remicade and Humira, work by suppress the immune system and come with an Food and Drug Administration “black box warning” informing patients of the treatment’s potential cancer risk as well as some life-threatening, opportunistic infections.

However, the current study suggested that anti-TNF therapy may not actually be associated with a “further increased cancer risk” and experts noted that larger studies of different populations with a longer follow-up must be done to confirm the results found in the latest research.

"While our findings show children with JIA have a higher incidence of cancer compared to peers without JIA, the greater frequency of malignancy does not appear to be necessarily associated with treatment, including use of TNF inhibitors," study author Dr. Timothy Beukelman said in a statement released on Monday.

Researchers are still unsure as to why children diagnosed with JIA have a heightened risk for cancer, and they said there are numerous possible explanations for the finding but he stressed that they have found no association between cancer risk and any treatments, like TNF inhibitors, for the condition.

Doctors have hailed TNF inhibitors to be revolutionizing treatments that have the potential to stop rheumatoid arthritis from progressing, but there have been numerous reports linking the use of the treatment to an increased cancer risk in children which prompted the FDA to issue a black box warning to these drugs in 2009.

The health agency issued a statement in April 2011 that said that it continued to receive reports of a rare cancer of white blood cells known as Hepatosplenic T-Cell Lymphoma or HSTCL, particularly in adolescents and young adults being treated with TNF blockers for Crohn’s disease and ulcerative colitis.

The research “highlights the critical importance of appropriate comparator groups when evaluating the safety of new medications,” Beukelman added.

The majority of the children with juvenile arthritis in Beukelman’s research were treated with injections of etanercept, a soluble TNF-receptor blocker, and Dr. Karen Onel and Dr. Kenan Onel from the University of Chicago noted in an accompanying journal editorial that other TNF-blockers that work by different mechanisms may produce different results.

However, "By focusing on the possible cancer risk associated with the use of TNF inhibitors, the underlying cancer risk associated with [juvenile arthritis] may have been understated, and it is important to make patients, families and physicians aware of the possible late consequences of this disease," they added in the news release.

The findings were published online Feb.13, in the journal Arthritis & Rheumatism.