Supporting Evidence-Based Care  

By Vandana Suresh | June 2025 

Advancements in drug discovery and research have changed the treatment landscape for juvenile idiopathic arthritis (JIA). However, some rare JIA subtypes and their associated complications still lag in optimal treatments. The low prevalence of these conditions, lack of clear clinical endpoints and disease heterogeneity lead to treatment variability. Adding to the complexity are the numerous medication options: How does a clinician choose which medication to use?  

“We have evolved to a situation where many different doctors treat pediatric patients with rare rheumatic diseases differently. The reason for that is that we don’t yet know the best treatment approach for many of our patients,” says Emily von Scheven, MD, pediatric rheumatologist at the University of California, San Francisco Benioff Children’s Hospitals. “Providers do what they think is best, or what they were trained to do by their mentors, or what they read about.” 

In rare disease research, consensus treatment plans (CTPs) can be valuable tools for guiding treatment decisions. Even more importantly, CTPs help reduce treatment variability and assist researchers in identifying treatments that are the most effective. Unlike randomized controlled trials, which are the gold standard for evaluating interventions, CTPs are standardized treatment plans that can then be evaluated in observational prospective studies, which are more time- and cost-effective.  

It is essential to note that CTPs differ from practice guidelines, which are established when there is sufficient research to determine the most effective therapeutic intervention. CTPs, on the other hand, are necessary for conditions where evidence-based medicine is lacking. 

The cornerstone to developing CTPs is getting providers to agree on the treatment plans to be tested. Consider a condition where a lack of an established standard of care has led to variability in treatment for patients with the same condition. To arrive at a CTP, these existing treatments are validated with literature review, and the prescribing details are delineated by healthcare providers using consensus methodologies, like Delphi surveys and consensus meetings. Once developed, CTPs are disseminated through peer-reviewed publications for use in general practice. They are then evaluated by practitioners through focused observational prospective studies to determine the best therapeutic intervention.  

For rare juvenile rheumatic diseases, CTP-based observational studies require collaborative efforts involving a network of institutions.  

“It’s challenging to assemble enough patients to have the sample size and power that you need to answer questions about what treatments are most effective,” says Dr. von Scheven. “We need to band together in pediatric rheumatology and pool all of our patients’ information from across the country.” 

With funding from the Arthritis Foundation, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) collects patient outcomes data using CTPs in the CARRA Registry, which includes over 70 active registry sites across North America. The registry has now enrolled more than 14,000 patients and has collected more than 1,450 biosamples associated with clinical data.  

“The registry allows us to collect data from patients in a prospective and uniform manner,” says Yukiko Kimura, MD, pediatric rheumatologist at the Joseph M. Sanzari Children’s Hospital at Hackensack Meridian Health. “Once we standardize the treatments using CTPs, pediatric rheumatologists can then collect and save data about the patients who are treated with CTPs using the registry and learn how effective they are.” 

For example, a recent prospective observational study called Start Time Optimization of Biologics in Polyarticular JIA (STOP-JIA), led by Dr. Kimura, compared the effectiveness of three CTPs, which differed by when biologics were started on untreated polyarticular JIA (pJIA) patients enrolled in the CARRA registry. The study shows that patients who received treatment according to the early combination CTP, where a biologic and methotrexate are started together, actually spent significantly more time with inactive disease than patients who followed the step-up CTP, where methotrexate was given first and a biologic was added only if needed. 

Currently, CARRA investigators have developed CTPs for 12 pediatric rheumatic conditions, including several forms of juvenile idiopathic arthritis, lupus nephritis, juvenile localized scleroderma and juvenile dermatomyositis. CTPs are revised when necessary if a particular treatment option in the CTP proves to be less effective or if a new drug becomes available on the market.  

“We want to understand the best way to treat our patients,” says Dr. von Scheven. “The registry and CTP activities are significant steps forward in the CARRA and the Arthritis Foundation’s research agenda aimed at improving outcomes in pediatric rheumatic disease.”