New studies testing the effectiveness of two biologics in children with systemic juvenile idiopathic arthritis (sJIA) have found that both drugs – tocilizumab (Actemra) and canakinumab (Ilaris) – result in major improvements. In some cases, kids felt better within a day.

“The results are thrilling. They are dramatic. They will be game changers for kids with sJIA,” says Daniel J. Lovell, MD, co-author of the studies and associate director of the division of rheumatology at Cincinnati Children's Hospital Medical Center.

Actemra was approved by the U.S. Food and Drug Administration (FDA) in 2011 for sJIA, a potentially life-threatening form of juvenile arthritis that causes inflammation in joints and organs, as well as fevers, rash and fatigue. But Dr. Lovell says that some pediatric rheumatologists have been waiting to see the results of larger clinical trials before prescribing Actemra in lieu of older drugs.

Ilaris is not FDA-approved for sJIA, but it is prescribed for the condition “off-label.” Novartis, the drug's manufacturer, says data from the trials form "the basis for worldwide regulatory submissions," which is "on track" in the U.S.

The new research – carried out by two international research networks, the Pediatric Rheumatology Collaborative Study Group and the Paediatric Rheumatology International Trials Organisation – was published recently in two articles in The New England Journal of Medicine. The first article detailed a randomized trial of tocilizumab, a drug that inhibits interleukin-6 (IL-6), a cytokine – or molecule – involved in immune and inflammatory processes. The study found that two-thirds of patients taking tocilizumab had significant improvement after just one dose. After a year on the drug, 80 percent of patients had no fever and an improvement in symptoms of at least 70 percent.

The second article detailed two randomized trials of canakinumab, which targets a different cytokine, interleukin-1 (IL-1), also involved in immune and inflammatory processes. The first trial, which lasted nearly a month, showed 84 percent of participants had marked improvement in symptoms after two weeks on the medication. The second (longer) trial showed 74 percent had no flares compared to those receiving placebo.

“With either treatment the systemic features resolved very quickly – from a few hours to a few days. In many cases you start the medicine in the morning and come back in the afternoon and the kids are feeling better. It’s extraordinary,” Dr. Lovell says. “It’s like these two agents are designer drugs for sJIA because the disease is driven by either interleukin-1 or interleukin-6, or a combination of the two. You can block either one and for 80 percent of these kids, it’s truly dramatically different. Their lives are profoundly different.”

Dr. Lovell says the results of these studies are especially encouraging because the improvements were seen in children who were treatment-resistant.

While older biologics – TNF inhibitors – are prescribed for some types of juvenile arthritis, they are not very effective in controlling the whole body (systemic) features of sJIA. Treatment with corticosteroids helps control the systemic symptoms, but used long-term, they carry a high risk of side effects, such as inhibited growth, high blood pressure and weight gain.

In both trials, the treatments allowed for a significant tapering of corticosteroids.

Dr. Lovell says long-term studies will look for answers to better understand long-term safety issues and address other questions, such as whether some patients have disease that is more closely linked to IL-6 or IL-1. “If you don’t respond to one of these agents, what are your chances of responding to the other? That’s an unknown question. That’s something that will need to be defined once the agents are out more in clinical use,” Dr. Lovell says.

Christy I. Sandborg, MD, a professor of pediatric rheumatology at Stanford University School of Medicine in Palo Alto, Calif., co-authored an editorial accompanying the studies that remarked on the impressive effectiveness of the drugs and the speed with which they helped children. But she agrees there is still a lot to learn about these medications.

“The question is, are they targeting the same thing? A similar step in the same pathway? Or are they targeting different things? And that’s something we don’t know,” Dr. Sandborg says.

She agrees long-term safety and efficacy need to be studied, especially if doses have to be increased over time. She also stresses that the medications didn’t help 20 percent of patients in these studies. “It doesn’t work in everybody. It’s not perfect. It’s not a silver bullet. But it’s pretty close to it,” Dr. Sandborg says.

“These drugs are incredibly effective. It really is a new era. And now it’s incumbent on us – doctors and the FDA – to monitor these agents to make sure that we understand the safety profile so that we can all make the best decisions and tailor the therapies,” she says.

Dr. Sandborg says one way to do that is through the Childhood Arthritis and Rheumatology Research Alliance (CARRA) – an organization of more than 350 pediatric rheumatologists and researchers in the U.S. and Canada committed to researching juvenile arthritis. So far about 60 centers are working with the group to enroll children in a registry to track symptoms and treatments. To find out more, visit carragroup.org.