The study included a stop strategy, meaning that children who had a 90 percent improvement in symptoms or inactive disease (as defined above) after three months were tapered off the medication. If symptoms returned, they were switched back to the daily regimen, and tapering was tried again in three to six months.

The results of the study were striking. Within three days, 18 out of 20 patients no longer had a fever and within a month, most showed at least a 90 percent improvement in symptoms. What’s more, the improvements persisted. After one year, 17 out of 20 patients had achieved clinically inactive disease, and 11 of them were able to stop medication.

Of the 14 children who were followed for two years, 12 of them were considered to be in clinical remission, either on medication (four patients) or off (eight patients). And of the 11 children who were followed for three years, 10 were in clinical remission either on medication (two patients) or off (eight patients).

Not all children responded so positively, however. Seven of the original 20 required some treatment in addition to anakinra to maintain a good response: Two had persistent inflammation that required the addition of corticosteroids (which were later discontinued); four relapsed after taking anakinra for about six months (and were switched to another biologic); and one relapsed after being tapered off anakinra. One patient from this group of seven died two years after joining  the study from macrophage activation syndrome (MAS), a rare, severe complication of sJIA.

The researchers say it’s not possible to explain why some patients fared better than others.

“SJIA is a heterogeneous and multifactorial disease,” Dr. Vastert notes. He says they looked at different characteristics, lab results and baseline symptoms to see if any difference at the start of the study could predict who would have a good response to anakinra, “but none of our parameters could predict this.”

Thomas Lehman, MD, chief of pediatric rheumatology at Hospital for Special Surgery in New York City, agrees that sJIA is a multifaceted and challenging disease to treat. “The development of a variety of biological agents, including anakinra, tocilizumab [an interleukin-6 inhibitor, sold as Actemra] and canakinumab, has substantially reduced the need for corticosteroids in the control of sJIA,” he notes. “Each of these agents has unique characteristics, and that two of the patients who failed anakinra responded to canakinumab while two others did not highlights the complexity of sJIA and the biologic mechanisms that underlie it.”

Still, he says, “Corticosteroids should no longer be the first-line therapy for severe sJIA. They will remain necessary for the children who fail biologic agents, but at least one and probably two or more biologics should be used before corticosteroids."

Carol Wallace, MD, a professor of pediatrics at the University of Washington School of Medicine and a pediatric rheumatologist at Seattle Children’s Hospital and a strong proponent of using biologics as a first-line therapy for sJIA, agrees.

“This is an important study. Yes, it’s small, but that’s not unusual because sJIA is uncommon and you have to get patients at a certain time – before they’re too sick,” she says. “Using anakinra as a first-line therapy is completely consistent with the recommendations of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) and the ACR. We now know that steroids are fraught with problems and are not a high-quality approach for patients. Biologics, on the other hand, have remarkably few side effects and can make an enormous difference in a child’s life, because patients who have their disease completely extinguished rapidly have the best outcomes. It’s exciting to finally see that in print.