The United States Food and Drug Administration (FDA) has approved the biologic drug canakinumab (Ilaris) to treat active systemic juvenile idiopathic arthritis (sJIA), an uncommon and especially serious form of arthritis in children. In addition to affecting joints, sJIA can affect the liver, lymph nodes and spleen and cause daily fevers and rash.

This is an expanded indication for canakinumab, a drug used to treat CAPS, or cryopyrin-associated periodic syndromes, a group of rare, inflammatory diseases. The drug’s approval for sJIA was approved based on two international phase III trials. The first, lasting four weeks, evaluated how well the drug worked in 84 children ages 2 to 19. By day 15, 84 percent of treated patients had experienced at least a 30 percent improvement in overall symptoms after a single canakinumab injection, compared with only 10 percent of patients who got placebo.

Daniel Lovell, MD, professor of pediatrics at Cincinnati Children's Hospital Medical Center and a study investigator, explains the importance of these results.

"Despite advances [in treatment] for other types of JIA, we really don't have good treatments for sJIA, the form that is most severe and associated with the highest mortality. It is the most severe because it truly is systemic – in addition to arthritis, children have all these other symptoms. They feel terrible, they often grow poorly because their appetite is suppressed and it is generally very debilitating. So to have effective therapies that control systemic features is a huge breakthrough," he says.

The second trial included steroid tapering (a gradual lowering of the steroid dose). Of the 92 children treated with canakinumab, more than 60 percent were able to substantially reduce their use of corticosteroids, including 46 percent who completely discontinued them.

Ronald M. Laxer, MD, professor of pediatrics and medicine at the University of Toronto, says this is significant because until recently, "many patients with JIA were dependent on corticosteroids for control of their disease. However, the side effects of steroid treatment can be as bad or even worse than the disease itself, including delayed growth and severe osteoporosis."

Dr. Lovell agrees.  "A statistically significant number of children were able to stop steroids, which is profoundly important, and those who continued taking them were on a very low dose with a much decreased chance of side effects," he notes.

Serious side effects of canakinumab were found to be similar to those of other biologics, with infection being the greatest concern. Dr. Lovell says the frequency and types of infection were not more severe than expected and must be weighed against the side effects of steroids.

In looking at the overall outcomes of the trial, he says, "All children in this study had longstanding, severe disease and had failed multiple therapies, including other biologics. To see this degree of rapid and significant improvement is very profound."

Canakinumab is an interleukin-1 beta (IL-1 beta) inhibitor. It works by blocking an immune system protein that plays a key role in some inflammatory disorders and is the second such drug approved for sJIA. Tocilizumab (Actemra), an interleukin-6 (IL-6) inhibitor, was approved for severe juvenile arthritis in 2011. (The FDA recently expanded the indication for tocilizumab to include another form of JIA.) Studies have demonstrated that both IL-1 and IL-6 play important roles in the development of the signs and symptoms of sJIA, Dr. Laxer notes.

Canakinumab, given as a monthly injection, is expected to cost $16,000 per dose (without insurance) – about eight times the cost of tocilizumab. Novartis, the drug's manufacturer, says it offers financial assistance to eligible patients unable to afford treatment.

While short-term studies show both drugs appear to be safe, there isn’t long-term evidence for their safety in sJIA – as with many newer drugs. But experts agree that having both on the market increases the odds of more children living healthier lives with this serious disease.

"To have two effective agents means we have more options to discuss with families and a much greater chance of having at least one therapy work,” Dr. Lovell says. “Now that these drugs are approved, we'll be able to introduce them earlier into treatment so children won't have active disease for such a long time and less duration of steroid therapy. I think the next decade will demonstrate a big change in the natural history and outcomes of this disease; I'm very excited about what the future holds for these kids."