Juvenile idiopathic arthritis increasingly is being shown to respond well to treatment, yet therapeutic hesitation on the part of nonpediatric rheumatologists is working to the detriment of these young patients, according to pediatric rheumatologists interviewed for this story.
The well-documented critical shortage of pediatric rheumatologists has real consequences in this disease, they said. Further, good results are impeded when physicians rely on therapies that work well in adults but not in children and when physicians hesitate to use newer therapies such as biologic agents.
For Dr. Lawrence K. Jung, the disparity in care became personal when he moved from Omaha, where he felt he had a handle on the close-knit JIA population, to Children's National Medical Center in Washington, D.C., where he became chief of the division of rheumatology in a metropolitan area of over 5 million people.
“I'm seeing so many patients who have not seen a rheumatologist in 2 years and have gone for long periods of time without good care,” he said.
“Most children with rheumatic conditions are still treated by pediatricians, internists, or adult rheumatologists,” said Dr. Andreas Reiff, chief of pediatric rheumatology at Childrens Hospital Los Angeles, “They are often misdiagnosed, or treated with drugs used in adults, such as Plaquenil, hydroxychloroquine, sulfasalazine, penicillamine, and steroids, which have been shown in a meta-analysis to be no better than placebo in children.”
“There is really a critical timeline here,” said Dr. Reiff. “It depends on the presentation and how quickly radiographic evidence develops, but we would usually start a child on biologics within 3 months of nonresponse or insufficient response or intolerance” to conventional treatments. Rarely would a nonrheumatologist act that fast.
Dr. Reiff said that his experiences at Childrens are an object lesson. For years, the hospital's rehabilitation center was filled with children with JIA who were there to receive splints and casts, undergo physical therapy, and recover from hip and knee replacement.
Last year, Dr. Reiff said, he resigned from his post as division head of the rehabilitation center. The reason:“Essentially, we had no more [JIA] patients there. Nowadays, we don't wait to treat kids until they're wheelchair bound and suffering severe joint problems.”
Dozens of studies presented at American College of Rheumatology meetings and summarized in a review article by Dr. Murray Passo (Curr. Probl. Pediatr. Adolesc. Health Care 2006;36:97–103) have documented the short- and long-term safety and efficacy of various biologic agents, including etanercept (Enbrel), approved for children with JIA in 1998, and adalimumab (Humira), which received pediatric approval from the Food and Drug Administration in 2008. Other biologics are also under study—and are sometimes used off label—for JIA, including infliximab (Remicade), an anti-tumor necrosis factor-alpha chimeric monoclonal antibody; anakinra (Kineret), a recombinant form of human interleukin-1 receptor antagonist; atlizumab, an anti-IL-6 receptor monoclonal antibody; and abatacept (Orencia), which selectively inhibits T-cell activation with the fusion protein CTLA41g.
“Many adult rheumatologists I work with may be very aggressive in treating arthritis in adults, but are unsure just how aggressive to be in children,” said Dr. Passo of the division of pediatric rheumatology at the Medical University of South Carolina in Charleston. “With children, there are long-term side effects to worry about.”
So far, the side-effect profile for children with JIA who take biologics has largely been benign, he said. Nevertheless, the drugs are new and their effect on children's health is not fully known.
The FDA is conducting an ongoing safety review of TNF blockers in children and young adults who are being treated for a variety of conditions. The FDA reported in a June 4, 2008, communication that 30 cancers—half of them lymphomas—had been reported in young people who were prescribed biologic therapies.
“Quite honestly, malignancy has not been a big issue” in the JIA population, said Dr. Passo. “The pediatric population does not have the same propensity for lymphoma as [do] adults with rheumatoid arthritis and lupus, at least not that we have been able to prove.”
Approximately 239 pediatric rheumatologists are licensed in the United States, but only about 125 of them treat patients, according to Dr. Reiff. At the same time, the American College of Rheumatology estimates that 300,000 children in this country have JIA. Simple arithmetic points to a level of need that is perhaps even greater than the 75% increase in the number of pediatric rheumatologists that was called for in a Department of Health and Human Services report to Congress in 2007.
At the time of that report, 13 states had no pediatric rheumatologist; 9 still don't, according to Dr. Passo. On average, families are required to travel 57 miles to see a pediatric rheumatologist.