Research Alert

New clinical research published online in the journal Arthritis and Rheumatology investigated three treatment approaches for a type of inflammatory arthritis in children called polyarticular juvenile idiopathic arthritis (pJIA). The study results showed improvements in pain and mobility with all treatment options, with potential increased benefits in disease activity using early combination therapy with biologic and non-biologic drugs together. The study was funded by the Patient Centered Outcomes Research Institute (PCORI).

Pediatric rheumatologist Dr. Yukiko Kimura, chief, Division of Pediatric Rheumatology at the Joseph M. Sanzari Children’s Hospital, and professor of pediatrics at the Hackensack Meridian School of Medicine, is the study’s lead investigator.


The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed three consensus treatment plans (CTPs) for pJIA patients who had not yet started any treatment. These CARRA pJIA CTPs served as the basis of the study. Named the “STOP JIA — Start Time Optimization of biologics in P-JIA”), it used the CARRA Registry to enroll patients and collect the necessary clinical data for the study.

The study compared the effectiveness of three treatment approaches that differed when biologics were started:

STEP UP CTP – initial non-biologic disease-modifying, anti-rheumatic drug (nbDMARD) monotherapy (such as methotrexate), adding a biologic only if needed after three or more monthsEARLY COMBINATION CTP – nbDMARD and biologic started togetherBIOLOGIC FIRSTCTP – biologic monotherapy The primary outcome of the study was achievement of clinically inactive disease (CID) without being on steroids at 12 months after starting treatment. Secondary outcomes included patient-reported improvements in pain and mobility, and disease inactivity as defined by the clinical Juvenile Arthritis Disease Activity Score (JADAS), as well as at least 70% improvement using the pediatric American College of Rheumatology (pACR) score.

The CARRA Registry collects information about children and young adults with pediatric-onset rheumatic diseases such as juvenile idiopathic arthritis (JIA), pediatric lupus and juvenile dermatomyositis (JDM). The purpose of the Registry is to learn about long- and short-term outcomes as well as the safety of medications used to treat these diseases. As of the Spring of 2021, more than 11,000 participants had been enrolled.

Across all three CARRA treatment approaches, there were no major differences in patients reaching the study’s main goal of achieving clinically inactive disease off steroid medications at the one year mark. All of the patients also had improvements in patient-reported pain and mobility on all three treatment plans. However, the secondary disease activity outcomes (clinical JADAS disease inactivity, and pACR 70% improvement score) were better in the patients who started on the EARLY COMBINATION approach, compared to the STEP UP regimen.

Inflammatory forms of arthritis (including rheumatoid arthritis and JIA) are believed to be caused by a combination of genetic and environmental factors. The underlying mechanism involves an autoimmune process by which the body’s immune system causes inflammation, pain and thickening of the joints. Polyarticular JIA causes inflammation in five or more joints within the first 6 months of the disease, and tends to get worse with time if not treated adequately. Biologics are a new class of drugs which are large, complex molecules, each of which targets specific receptors and other molecules on immune cells that cause inflammation, while traditional disease-modifying drugs (nbDMARDs) for inflammatory arthritis are conventional, less targeted small-molecule drugs, and have generally been in use before biologics were developed.

The main results showed that of 400 patients enrolled at 56 CARRA registry sites in the U.S. and Canada, most patients (64%) chose and began the most traditional STEP UP treatment, followed by EARLY COMBINATION (25%) and then BIOLOGICS FIRST (11%). The treatment started was a shared decision made by the health care provider, family and patient together.

In all three treatment groups, patients had less pain and greater mobility after one year, and less than half of the patients achieved Clinically Inactive Disease (CID). While the number of patients achieving CID did not differ significantly among treatment groups at 12 months, the EARLY COMBINATION group had the highest percentage of patients who achieved this outcome. The EARLY COMBINATION group also had a significantly higher likelihood of achieving other disease activity and response measures (such as the JADAS inactive disease and the pACR 70 percent improvement score) when compared to the STEP UP and BIOLOGIC FIRST groups.

A second article published in the same issue by CARRA investigators and co-authored by Dr. Kimura, “Improved disease course associated with early initiation of biologics in untreated polyarticular Juvenile idiopathic Arthritis: A trajectory analysis of the STOP-JIA study,” showed that patients who started biologics early within the first three months of baseline, had a significantly higher likelihood of having the best trajectory toward disease inactivity.


In October, Dr. Kimura will be honored by the Arthritis Foundation with its Champion of Yes! Award, which is their lifetime achievement recognition. In November, the American College of Rheumatology will honor Dr. Kimura as a member of its 2021 class of Masters of the American College of Rheumatology, one of the highest awards the college bestows.

In addition to being the Division Chief of Pediatric Rheumatology at the Joseph M. Sanzari Children’s Hospital, Dr. Kimura is a Childhood Arthritis and Rheumatology Research Alliance (CARRA) leader and researcher. Currently, she is co-principal investigator of the CARRA Registry and the co-chair of the CARRA Research and Registry Oversight Committee.

Dr. Kimura is also a past President of the CARRA network.

The CARRA Registry allows children with pediatric rheumatic diseases from across North America and beyond to participate in research about their diseases. This can include sharing their identity-protected health information, patient reported outcomes, potential treatment-related side effects and blood samples. Researchers can then use this information to better understand and treat pediatric rheumatic diseases.

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Arthritis and Rheumatology