Doctors have long known that even when children with juvenile rheumatoid arthritis, or JRA, achieve remission, they have a high risk of relapse when taken off their medication.
As a result it has been standard practice for most kids to stay on their methotrexate for at least one year after their symptoms disappear.
But a study presented at the 2009 annual meeting of the American College of Rheumatology in Philadelphia, has concluded that the extra year on medication doesn’t really affect the risk of relapse – a finding that may allow more JRA patients to come off methotrexate as soon as their disease subsides.
For this study, Dirk Foell, MD, of the Department of Pediatrics at the University of Muenster in Germany, and his team set out to determine if the length of treatment after reaching inactive disease status influenced the risk of future recurrences and whether patients at risk for flares can be identified by molecular biomarkers.
Scientists studied 365 JRA patients whose disease had been inactive for at least three months. Patients were split into two groups. One stopped methotrexate after six months, the other after 12. When participants were taken off the medication, myeloid-related proteins 8 and 14 – which are markers for inflammation – were analyzed.
Of the 297 patients who completed the study, roughly half in each group saw their arthritis flare again – 54.3 percent of the group continuing on methotrexate for six months and 43.7 percent of those taking it for a year saw the disease return.
“Longer treatment with methotrexate in remission does not prevent flares after withdrawing therapy in juvenile idiopathic arthritis,” Dr. Foell says. “We say that children should be taken off medication earlier when they are in remission, and that novel biomarkers may be used to help with this decision.”
Study authors found that traditional blood tests, C-reactive protein or CRP, and ESR, or “sed rate”, couldn’t accurately tell them who was at risk of relapse. “All of our patients had normal CRP, although clearly the outcome with regard to disease flare differed. Hence, CRP is not able to detect subclinical, minimal inflammation and cannot be used to further differentiate between patients at risk for flares and those who stay in remission,” Dr. Foell explains.
But scientists did find that measuring myeloid-related proteins 8 and 14, or MRP 8/14, which are markers of inflammation, could accurately predict which children would relapse, and which could safely come off their meds. These proteins were significantly higher in those patients who subsequently relapsed compared to patients with stable remission.
“MRP 8/14 is the first biomarker reflecting subclinical inflammation in remission,” Dr. Foell says. ”Novel molecular markers of inflammation may at least give more certainty about the fact that there are no signs of ongoing inflammation, and that will help with decision making.”
Unfortunately, the blood test for these proteins is still experimental and is not yet available for clinical use.
“We can’t use it right now but it’s a little promising for the future,” explains Lisa Imundo, MD, director of the Division of Pediatric Rheumatology at Columbia University Medical Center in New York City.
Despite the fact that the blood test isn’t readily available, Dr. Imundo says this study is helpful.
“We do notice with methotrexate in particular, that a good percentage of patients flare up again. There have never been any studies about what we should do. So this shows us what we’ve all found – that sometimes a lot of patients can’t come off the methotrexate. They need to continue on it.”
She says there is some positive news here as well. “If a patient is doing well, you don’t have to wait to take away the methotrexate. That’s sort of good news for some patients. This study shows there’s no added reason to continue the medication for an additional year,” she explains. “There are patients who could definitely stop earlier. That’s the good news. But the bad news is, even if you are asymptomatic and have no arthritis on the medication, about 50 percent of patients wont be able to come off [the medication].”
“I think it’s pretty much what we see in practice. That we hope we can stop the methotrexate but there’s always a group of patients that relapse and need to stay on the methotrexate,” Dr. Imundo adds.