"Our study showed that both methotrexate and leflunomide can be used safely and effectively in children. In fact, in our study both drugs had a higher response rate in children than the response rate reported in studies in adults," said Dr. Silverman, the study's lead author, a rheumatologist and senior associate scientist at Sick Kids, and a professor of Paediatrics at the University of Toronto. "A higher percentage of patients responded to methotrexate, so this would be the medication to try first in children, but leflunomide is a good alternative for patients where methotrexate doesn't work or isn't tolerated. Importantly, we have identified a new, safe, effective oral therapy for use in children with chronic arthritis."
The study also showed that a higher dose of methotrexate than previously thought can be used safely in children and that at the increased dose there was increased efficacy. Establishing drug dosages in children is more complicated than adults due to the wide variation in weight between a baby and a teenager.
Patients three to 17 years of age with polyarticular-course rheumatoid arthritis (where arthritis affects at least five joints) were recruited to the study at 32 centres in 13 countries. The children were given either methotrexate or leflunomide, medications that are DMARDs (disease-modifying anti-rheumatic drugs), which work by altering the immune system. Methotrexate is the most commonly used DMARD in children. DMARDs are a stronger class of arthritis medications than NSAIDs (nonsteroidal anti-inflammatory drugs).
"Most medications are never designed for children and are rarely tested in children. However, children do get severe arthritis that requires medications beyond NSAIDs. The only way to properly assess a medication for children is through a randomized, controlled trial. The 'Pediatric Rule', enacted by the U.S. Congress and supported by the Food and Drug Administration (FDA), has increased the number of drug trials in children with arthritis," added Dr. Silverman.
Juvenile rheumatoid arthritis is a chronic disease that causes pain, stiffness and swelling in more than one joint. It affects approximately one out of every 1,000 Canadian children.
This study was supported by Sanofi-Aventis, with salary and infrastructure support for Dr. Silverman provided by Sick Kids Foundation.
The Hospital for Sick Children, affiliated with the University of Toronto, is Canada's most research-intensive hospital and the largest centre dedicated to improving children's health in the country. Its mission is to provide the best in family-centred, compassionate care, to lead in scientific and clinical advancement, and to prepare the next generation of leaders in child health.
Journal
New England Journal of Medicine