Drugs Hold Promise for Severe Juvenile Arthritis Patients

Children who suffer from a rare and painful form of arthritis that's accompanied by fever and rashes may soon have more treatment options.

Two studies published in a recent issue of the New England Journal of Medicine suggest that two drugs-canakinumab and tocilizumab reduce symptoms, including severe joint pain experienced by children with systemic juvenile idiopathic arthritis (JIA).

The disease is one of seven types of juvenile idiopathic arthritis that affect one in 1,000, or roughly 294,000, children in the United States, according to the US National Institutes of Health. It is characterized by inflammation of one or more joints, fever and rash, among other health problems. "Idiopathic" means the cause is unknown.

"Systemic juvenile idiopathic arthritis is a form of severe arthritis that until a few years ago was treated mainly with corticosteroids, which have known side effects, especially growth impairment," said Nicolino Ruperto, MD, a pediatric rheumatologist at G. Gaslini Children's Hospital in Genoa and coauthor of the studies.

Two Drugs May Bring Needed Relief

The research looked at the safety and effectiveness of the interleukin-1 inhibitor canakinumab and the interleukin-6 inhibitor tocilizumab.

In the canakinumab study, funded by drug maker Novartis Pharma, two trials took place. In one, patients received the drug subcutaneously injected just below the skin) or a placebo. In the other, canakinumab was taken knowingly, or open-label.

"The study demonstrated that among 190 children with systemic JIA, about 60% of the children treated for several months had a complete disappearance of both arthritis, fever and rash," said Dr. Ruperto. One-third also discontinued corticosteroids, he said.

Dr. Ruperto said canakinumab works by reducing the level of a cytokine la protein) called interleukin-1 that leads to the inflammation–the arthritis and fever-in children with systemIc Juvenile idiopathic arthritis.

In the study of tocilizumab, researchers from the Ospedale Pediatrico Bambino Gesu, a children's hospital in Rome, randomly assigned 112 children, aged two to 17, with systemic juvenile idiopathic arthritis to one of two doses given intravenously or a placebo every two weeks for three months. Patients who did not respond were offered the drug open label after that and followed for about a year. At 12 weeks, 71% who received tocilizumab had no fever and improved pain compared with 8% in the placebo group. The drug maker Hoffmann La Roche funded this study.

What Experts Say

The research breaks new ground, according to Christy Sandborg, MD, and Elizabeth Mellins, MD, both from Stanford University, who wrote an accompanying journal editorial. "There is no doubt that the agents tested in these trials signal a new era in the treatment of systemic JIA and will shed light on the mechanisms driving this enigmatic disorder," they wrote.

But Drs. Sandborg and Mellins also said important questions remain about the drugs' side effects, and they noted that some children in the trials experienced macrophage activation syndrome, a serious, systemwide inflammation that is a complication of JIA and could also be related to the interleukin drugs.

Patience White, MD, vice president for public health at the Arthritis Foundation and a professor of pediatrics and medicine at George Washington University School of Medicine and Health Sciences, said, "These trials are very exciting because the response rates are much better than responses to other biologic drug trials to date."

Still, concerns exist. "While it is exciting work, from a parent point of view, it can be an anxiety-provoking decision to decide to start their child on a new drug for which the full side-effect profile is not known," she said.

Dr. White said that neither drug has a long track record in treating this condition, and unknown side effects don't always arise in early drug trials. Mass-market use sometimes reveals additional pros and cons of a medication.

She said families interested in trying the interleukin drugs should first sce a physician who specializes in juvenile rheumatology. "See someone who knows about these drugs, and make sure your child is part of a registry so that everybody learns from the experience with it," she said.

What’s Available Now And What’s To Come

Currently, only tocilizumab is approved to treat systemic juvenile idiopathic arthritis, said Dr. Ruperto. For canakinumab, the evaluation process is ongoing in the United States and Europe. If it's approved, he said, "It is likely that insurance companies will have to pay for it."

"Before this," said Dr. White, "we really haven't had drugs that really made that much difference whereas these clearly do. The beauty of these trials is that they're opening up opportunity to see the results of targeting new steps in the inflammatory process.