October 2016

Removing Roadblocks to Advance Research in Juvenile Spondyloarthritis

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Sometimes in medicine, it’s all about the way you look at things. Not noticing a subtle finding on an X-ray, for instance, can result in a missed or delayed diagnosis. On the other hand, radiology overcalls can lead to unnecessary treatments. Large variations often occur in the interpretation of imaging results for children and adolescents suspected of having juvenile spondyloarthritis (JSpA), even by the most experienced radiologists.

Children with JSpA experience inflammation and stiffness of joints that can result in growth disturbances and loss of range of motion if not controlled properly. They tend to develop arthritis of lower extremities and are as at risk of developing arthritis of the lower back or spine (sacroiliac joint). JSpA is associated with more frequent and higher intensity pain and poorer quality of life than other categories of juvenile arthritis. Biological medications, such as anti-tumor necrosis factor agents, can have a beneficial effect on JSpA’s inflammatory features, but clinical evidence supporting their use mostly comes from studies of adult patients.

“There is a critical need not only to accurately diagnose these children, but also to identify the impact of expensive biologics,” said Pamela Weiss, MD, MSCE, an attending physician in the division of Rheumatology at Children’s Hospital of Philadelphia, a core faculty member of the Center for Pediatric Clinical Effectiveness at CHOP, and an associate professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania.

Research in JSpA has encountered several roadblocks that Dr. Weiss is starting to chisel away at with the help of an Innovative Research Grant from the Rheumatology Research Foundation, a charitable organization dedicated to advancing treatment for patients living with rheumatic disease.

First, clinicians and researchers lack age and gender reference data for the appearance of the sacroiliac joints in the growing skeleton. The study team will scan 60 children across a range of ages (8 to 18 years) with magnetic resonance imaging (MRI) to compile a detailed assessment of what these joints look like in healthy children. This project aim is “desperately needed in this field,” Dr. Weiss said.

“Even at CHOP, which is one of the top children’s hospitals in the U.S., we encounter variation in terms of how images of the sacroiliac joints are interpreted,” Dr. Weiss said. “If there is variation here, you can imagine that variation may be even greater at other institutions without as much expertise in musculoskeletal imaging. The impact of our research could be far-reaching.”

Early signs of inflammation due to spondyloarthritis do not usually show up on X-rays, and if mild changes do appear, they are easily overlooked. Most radiologists and rheumatologists agree that MRI imaging is a more sensitive tool for detecting early disease inflammation in JSpA, Dr. Weiss said, yet most insurance companies still insist that X-rays be performed first before they will agree to pay for a MRI. Requiring X-rays that are potentially not useful is a costly practice that also subjects young children to unnecessary radiation exposure, Dr. Weiss added.

The study team will assess the overall utility of X-rays in the initial evaluation and management of sacroiliitis by delving into CHOP’s imaging archives from 2005 to 2016. They will review the imaging results of children who were seen by orthopedics or rheumatology for suspected early arthritis of the sacroiliac joints and had a pelvic X-ray and a pelvic MRI performed within six months of each other. The researchers will track the number of sacroiliitis cases that would have been missed by relying solely on X-rays. They also will look out for patients who were identified as being positive on X-rays, but who actually were negative on MRIs.

“It would be enormously helpful to definitely show that X-rays don’t really play a role in screening and evaluating children for early inflammatory sacroiliac disease,” Dr. Weiss said. “That would be practice-changing.”

Another obstacle is that rheumatologists oftentimes must borrow from adult medicine research findings in order to demonstrate to insurance companies the efficacy of biological agents for use in children with JSpA. The study team will partner with the University of Alabama to assess the impact biologics had on a group of children diagnosed with JSpA who also had an MRI prior to or very early in the course of their treatment.

The researchers will try to establish proof of concept that when children with JSpA start biological medication, the inflammation seen on the MRIs improves or completely resolves. The study’s findings will lay the groundwork for future prospective studies to evaluate these changes more objectively and standardly.

By addressing these gaps in knowledge, Dr. Weiss hopes that she will build enthusiasm among other clinicians and scientists to pursue this unique research niche. The current project involves experts from both rheumatology and radiology, and she is excited to collaborate with Nancy Chauvin, MD, director of Musculoskeletal Imaging with the department of Radiology at CHOP, and David Biko, MD, an attending radiologist in the department of Radiology. Together, they will ensure that development of effective and targeted intervention strategies for JSpA to prevent irreversible damage of children’s axial joints does not remain at a standstill.

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