Starting juvenile arthritis (JA) treatment with a combination of three powerful meds at once – instead of with the least potent arthritis drug and progressing from there – might give some parents pause. That’s a lot of medication for little, growing bodies. But when it comes to JA that affects at least five joints – called polyarticular arthritis – treating it aggressively offers the best chance of knocking the disease down to undetectable levels, according to a study presented at the 2011 scientific meeting of the American College of Rheumatology, or ACR.
In the study of 85 children ages 2 to 16 with polyarticular arthritis, those treated early with a combination of three potent drugs performed better than those who began with one drug. In fact, 71 percent of those on methotrexate, etanercept, or Enbrel, and prednisone improved 70 percent in four months, compared with 44 percent of patients on methotrexate alone.
After six months, 40 percent of patients on the combination cocktail, but only 23 percent of those on methotrexate alone, had clinically inactive disease. The difference after six months between the two groups isn’t statistically significant, meaning that chance can’t be ruled out. However, because a third of all of study patients had clinically inactive disease by six months, researchers call it another vote for aggressive, immediate treatment.
Early Treatment Lowers Risk
JA experts say an early, aggressive treatment regimen probably carries less risk than uncontrolled JA, which can cause irreversible joint destruction.
“Some doctors treat JA patients first with a nonsteroidal anti-inflammatory drug. If satisfactory relief isn’t achieved, then physicians quickly prescribe methotrexate before trying biologic drugs,” says study co-author Edward Giannini, MD, professor in the division of rheumatology at the Cincinnati Children’s Hospital Medical Center. That is in keeping with guidelines from ACR. But Dr. Giannini says this study shows that early, aggressive treatment improves the odds of remission.
At the study’s four-month mark, those patients who took only methotrexate, were given the other two drugs if they didn’t reach 70 percent improvement. This four-month delay in getting the most aggressive treatment with the combination cocktail reduced the chance of making the disease undetectable, researchers found. In fact, the chances for remission increased by 30 percent for each month sooner that treatment was started.
The study’s lead researcher, Carol Wallace, MD, professor of pediatrics at Children’s Hospital and Regional Medical Center in Seattle, says the study shows that treating earlier is better than treating later and that “there is truly an advantage to treating aggressively rather than starting slow and ramping up.” Also the study gives physicians a clear definition of “aggressive,” Dr. Wallace says.
“I hope they will see what they previously thought was aggressive isn’t really aggressive,” Dr. Wallace says. “For every month earlier a child is treated, they have a greater chance of achieving inactive disease by six months.”
Although there are other biologics, also called anti-TNF drugs, approved for treating arthritis, etanercept was chosen for this study because it was the first in its class approved for use in children and therefore has the most safety and effectiveness data. Dr. Giannini says the drugs have manageable side effects and the potential risk pales in comparison to the severe, irreversible, disabling damage caused by untreated juvenile arthritis.
“We were shooting for inactive disease,” he says. “Ours was a very high goal. We couldn’t have dreamed of that after only six months of therapy before biologics. Our conclusion is that early, aggressive therapy with a biologic, methotrexate and a little bit of prednisone enhances and increases the probability that we can turn off the disease quickly.”
Window of Opportunity
Timothy Beukelman, MD, associate professor in the Division of Pediatric Rheumatology at the University of Alabama at Birmingham, is not entirely surprised by the study findings. “Many pediatric rheumatologists, myself included, believe in the concept of a window of opportunity in the treatment of JIA. This means that early, aggressive therapy to rapidly bring the disease under control may, in fact, have benefits may years into the future.”
“This study confirms our clinical suspicion that early, aggressive therapy results in better outcomes,” says Dr. Beukelman, who was not involved in the study. “One thing we learned from this study is that even a one-month delay in initiating aggressive therapy had significant impact on short-term outcomes.”
Harry L. Gewanter, MD, a pediatric rheumatologist in private practice in Richmond, Va. and a Mid-Atlantic Region board member of the Arthritis Foundation, says this study provides concrete guidance on the best way to treat these young patients. “We all thought this was the way to go, now we have some data,” says Dr. Gewanter, who was also not involved in this study. “The outcomes weren’t good with starting low and slow and moving your way up.”
This information is particularly valuable to physicians who aren’t pediatric rheumatologists who may encounter children with juvenile arthritis, because of the lack of specialists in this area. For example, there are only a half dozen pediatric rheumatologists in the state of Virginia, Dr. Gewanter says, so some young patients may be treated by adult rheumatologists. For general practitioners who may not immediately recognize the signs of juvenile arthritis, Dr. Gewanter says the main message is: “If a child comes in with a swollen joint that won’t go away, don’t blow it off.”