The U.S. Food and Drug Administration (FDA) recently approved the biologic drug tocilizumab (Actemra) for the treatment of polyarticular juvenile idiopathic arthritis (JIA) in children age 2 and older. JIA is the most common type of pediatric arthritis, which collectively affects approximately 294,000 children in the United States. About 30 percent of them have the polyarticular form, which causes pain and stiffness in at least five joints, most often in the hands and feet.

Tocilizumab, which blocks a protein called interleukin-6 (IL-6), is already approved for adult rheumatoid arthritis (RA) and the systemic form of JIA. The decision to expand its use is based on data from a two-year multinational trial called CHERISH, which evaluated the drug’s safety and effectiveness for children with polyarticular arthritis.

In all, 188 patients ages 2 to 17 participated in the study. All had active arthritis that failed to respond to methotrexate, a standard treatment for JIA.

“The first 16 weeks of the trial were open-label – all patients received the drug,” says pediatric rheumatologist Timothy Beukelman, MD, an associate professor of pediatrics in the division of rheumatology at the University of Alabama at Birmingham School of Medicine. “Approximately 90 percent [of them] had an adequate response.” This means at least a 30 percent improvement in symptoms, as measured by American College of Rheumatology (ACR) criteria, which rate improvements in joint pain and swelling, functioning, inflammation markers and overall well-being.

Children who responded adequately were then randomized into two groups, with half continuing to receive tocilizumab and the other half receiving placebo. During this phase, any child on placebo whose symptoms flared could return to tocilizumab, a common practice in pediatric trials. In fact, the placebo group experienced almost twice as many flares as the tocilizumab group did – 48 percent compared with 26 percent.

At the end of the randomized phase, a 30 percent improvement was seen in 74 percent of those treated with tocilizumab and in 54 percent on placebo. A 70 percent improvement was seen in 65 percent of kids on tocilizumab, compare and in 42 percent on placebo. The trial then continued in a follow-up phase for an additional 64 weeks.

Dr. Beukelman notes that, although researchers look for the 30-percent improvement in JIA studies, doctors are not satisfied with anything less than a 75 percent clinical improvement. “In the era of biologics, the goal is inactive disease – no detectable arthritis,” he says. “This is achievable much of the time, but that level of response isn’t always durable. We can achieve it, but not necessarily maintain it month after month.”

The safety profile of tocilizumab, given as a monthly infusion, was similar to other biologic drugs’, with infection being the most common serious side effect. Tocilizumab also can cause lower blood cell counts and elevated liver enzyme levels, which are problems not usually seen with tumor necrosis factor (TNF) inhibitors such as etanercept (Enbrel) and adalimumab (Humira), the biologic medications most often used to treat JIA.

“It’s not clear how important these lab abnormalities are,” Dr. Beukelman says. “They can be a reason for stopping treatment [but] there are also ways of dealing with them if they get too large.”

He adds that the trial outcomes and subsequent FDA approval mean not only that tocilizumab is effective for polyarticular arthritis, but that the drug will probably be covered by insurance. Tocilizumab, like other biologics, can cost tens of thousands of dollars per year for patients paying out of pocket.

“Most insurers have covered FDA-approved biologics, and I anticipate that this will be no different,” Dr. Beukelman says.

He is not sure how tocilizumab will fit into treatment protocols for polyarticular JIA.

“Based on years of experience and comfort with TNF inhibitors, most pediatric rheumatologists will continue to use them as a first-line treatment for JIA. But tocilizumab is an option after an incomplete response to TNF inhibitors. The overall impact may not be large, but for the individual patient not doing well on currently available biologics, it could be a huge improvement,” he says.

Christy Sandborg, MD, professor of pediatrics at the Lucile Packard Children’s Hospital at Stanford University School of Medicine in Palo Alto, Calif., agrees. “The approval of Actemra for polyarticular JIA is an important expansion of our biologic armamentarium for children, providing an agent that targets a different cytokine, interleukin-6,” she says.

Having many choices is the best way to ensure good outcomes for the greatest number of children, according to Yukiko Kimura, MD, chief of pediatric rheumatology at the Joseph M. Sanzari Children’s Hospital in Hackensack, N.J.

“Each patient not only may have preferences, but may respond differently to any given treatment,” says Dr. Kimura. “The next step is to understand how each of these extremely effective treatments compares to each other in terms of overall effectiveness and safety, and ultimately to be able to know which patients with JIA will respond best to a particular therapy.”