Developing new treatments for kids with arthritis is challenging. Drugs that work for adults may not work the same way in children. Ask any pediatrician and they will remind you that kids are not just small adults. Children are still growing and developing. They are different sizes and at different stages of development, which makes dosing and safety considerations more challenging. The types of additional medical conditions children experience may be very different from the conditions seen in adults.
Add to these considerations the fact that juvenile arthritis (JA) is considered a group of rare diseases; in the U.S., fewer than 300,000 children under the age of 18 currently have some form of a rheumatic disease. It’s harder to develop drugs when you have fewer patients to test them on through traditional U.S. Food and Drug Administration (FDA) pathways.
传统的FDA药品审批过程涉及一系列的研究，在药物提交FDA批准上市之前需要进行一系列的研究。在适当的实验室和动物试验之后，人体试验通常从在少量健康志愿者中进行的第一阶段研究开始，以确定安全性。第二阶段研究通常会在数百名患者身上测试一种实验性药物，以收集更多的安全性和有效性数据。第三阶段的研究包括在数千名患者身上测试一种实验性药物，以收集更多的安全性和有效性数据。
成功通过这些阶段的药物可以提交给FDA审批。这个过程非常耗时，一种新药需要长达20年的时间才能研制成功;大多数实验性药物都做不到这一点。虽然通过动物实验，实验药物似乎可以安全使用，但许多药物在人类身上的安全性或有效性测试都失败了。
According to Guy Eakin, PhD, Arthritis Foundation vice president of scientific strategy, this problem is at the core of JA drug development. “We have a tremendous paradox in drug development,” he points out. “The advances made over the last two decades have provided many children with an improved quality of life. Today, the next generation of therapeutics must contend with the fact that many patients are stable and will not opt to enroll in a clinical study during periods of stability.”
On Oct. 2, Dr. Eakin served as a panelist to discuss the issues surrounding drug development for juvenile idiopathic arthritis (JIA, the most common form of JA) at a one‑day workshop co-hosted by the FDA and the University of Maryland. The workshop, “Accelerating Drug Development for Polyarticular JIA,” featured discussions and presentations about the regulatory aspects of drug development for this special population, as well as presentations on different study models that have been recently used in developing drugs for pediatric patients.
Laura Schanberg, MD, an Arthritis Foundation-sponsored CARRA (Childhood Arthritis and Rheumatology Research Alliance) investigator and professor of pediatrics at Duke University School of Medicine, presented an overview of safety assessment considerations for studying treatments for polyarticular JIA. Dr. Schanberg addressed central questions about the different ways to approach research: the traditional approach compared to collecting real world data through registries, claims data and electronic health records. She contrasted the ways in which drug safety testing in children is different from drug testing in adults. The presentation also covered the concerns that doctors, patients and parents have when using drugs on immature body systems.
According to Dr. Schanberg, health care providers and families have serious concerns about how drugs affect growth, bone health, puberty and future reproductive health and immune system development, as wellas how long-term use of a drug may increase risks for developing more serious conditions. She concluded by saying: “The safety issues we are most concerned about are rare or very rare, so we need to study as many kids as possible for as long as possible. Robust post-marketing real world data sources, such as disease-based registries, will provide the most useful long-term safety data.”
Dr. Nikolay Nikolov, associate director for rheumatology at the FDA, explained the importance of the meeting. “Having this public workshop – to better understand the state of science, existing knowledge gaps and what, if any, uncertainties exist in JIA drug development – is critical to ensure that new safe and effective therapies continue to be made available to toddlers, children and adolescents with JIA.”