New Study Looks at Remission in Patients with Juvenile Rheumatoid Arthritis

Thanks to a number of new biological therapies, more children who have juvenile rheumatoid arthritis (JRA) have experienced remission of their symptoms. However, this state of remission had not been well-understood up until this point. Now, a new study has provided the first genomic characterization of remission in patients with juvenile rheumatoid arthritis.

According to James N. Jarvis, the lead author of this RA clinical study, this state of remission does not mean that these patient’s immune systems have recovered. “It turns out that even though these children in remission appear to be perfectly normal and symptom-free, their immune systems are still perturbed,” states Jarvis.

What Does Achieving Remission Mean?

This rheumatoid arthritis clinical study acknowledges that nearly 50 percent of children diagnosed with JRA can achieve this state of remission while being treated with the standard treatments available for this chronic inflammatory disease.

“Our study provides some insight into why so many children in remission experience disease flares even when their disease has been stable for weeks or months, and why 50 percent of children who try to come off medication experience disease flares within two to six months,” says Jarvis.

This clinical study was conducted at the University of Oklahoma Health Sciences Center by Jarvis and a team of colleagues. Although, none of this research would have been possible without the support of the Oklahoma Center for the Advancement of Science and Technology, the National Institutes of Health, and the Arthritis Foundation, which will also be funding Jarvis’ continued research in this area. Following this study, Jarvis and a number of his team members have begun working at the University’s Clinical and Translational Research Center.

A New Look at Remission in Juvenile Rheumatoid Arthritis

The study looked at how the gene-expression profiles from two different cohorts (each with 14 patients in remission from JRA compared to those of 15 individual controls. Also, these patients were on two different medication regimens. The patients were monitored every two to three months over the course of at least one year.

“Remission, of course, is our goal,” claims Jarvis. “I like to say it’s hard to get somewhere when you don’t know where ‘somewhere’ is. My lab is trying to build a ‘genomic roadmap’ for what remission is and exactly how we get there. That way, we can find a way to get these children into remission more quickly and for longer periods.”

This latest RA study has supported previous research by Jarvis, which suggested that this state of remission experienced by children with JRA was not actually a return to normalcy, but actually a separate biologic state. This study has found that this biologic state is the result of pro-inflammatory responses being canceled out by the anti-inflammatory responses produced by the gene-expression alterations that medication causes.

Variables Affecting Remission in JRA

Another important discovery from this study is that this remission state is dependent on HNF4a, a transcription factor that binds to DNA, in turn functioning as an “on” or “off” switch for gene expression. Prior to this research, HNF4a was viewed simply as a regulator of metabolism in pancreatic cells and liver. Now, Jarvis believes that this finding suggests that HNF4a is a member of what could be a cohort of master switches that regulate therapeutic response.

This rheumatoid arthritis clinical trial identified more than 200 genes in white blood cells that were expressed differently in children who were prescribed a combination treatment of methotrexate and a biological drug called etanercept compared to healthy subjects of the same age. A number of these expressed genes will also bind to HNF4a.

Jarvis believes that these discoveries will help to ensure that future research can identify specific biomarkers which play a role in determining how patients will respond to various therapies. “This is a first step toward the goal of identifying biomarkers that will ultimately allow clinicians to personalize treatment by predicting which patients will respond best to which therapies,” he says.

Currently, Jarvis and his team are working with a $1.2 million NIH grant to study study microarray-based biomarkers in juvenile idiopathic arthritis. In his spare time, he is also looking into the role that epigenetics can play in juvenile rheumatoid arthritis.