Estimating heterogeneous treatment effects of biologic and targeted synthetic disease modifying drugs from multiple clinical trials in Juvenile Idiopathic Arthritis

Juvenile Idiopathic Arthritis (JIA) refers to a group of long-term conditions that cause joint inflammation in children. It affects about 1 in every 1,000 children. The cause is unknown, and there is currently no cure. Over the past 20 years, treatment has improved significantly with the introduction of biological disease-modifying antirheumatic drugs (bDMARDs). Targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) is a new class of medication that offers a convenient alternative to other treatments. These medicines can decrease the amount of inflammation in the body and reduce the damaging effects of arthritis on the joints by restricting the immune system inflammation response. Without bDMARDs and tsDMARDs, inflammation in the body could eventually lead to destroyed joint tissues. They have been shown in randomized controlled trials (RCTs), studies where patients are randomly assigned to different treatments, to work better than older treatments or no treatment. However, despite these advances, nearly half of children with JIA still experience active disease. Not all treatments work the same for every child. JIA includes different types of disease, and children vary in their symptoms and characteristics.

Although RCTs are the gold standard for testing how well treatments work overall, they are often not large enough to show how treatments work in specific subgroups of patients. In addition, participants in clinical trials may not fully represent the wider population of children with JIA. To overcome these challenges, we will combine data from multiple RCTs with real-world data (RWD) collected from large patient registries and from electronic health records (EHRs). The RWD in this study contains data from a large U.S. pediatric rheumatology clinic that has followed patients with non-systematic JIA for over 10 years. These records provide a sample of general patient population, which may not be captured in the randomized trial sample, and include important details such as patient age, lab test results, medication use, and scores measuring arthritis activity, including the clinical Juvenile Arthritis Disease Activity Score 10 (cJADAS10). In this study, we will apply and compare statistical methods to explore which children benefit most from bDMARDs and tsDMARDs. We will use advanced, flexible methods to consider the RWD obtained from routine clinical care.

This research will help us better understand which treatments work best for specific subgroups of patients. Our goal is to support more personalized and effective treatment strategies for children living with JIA.