Ask 10 pediatric rheumatologists how to treat a child with arthritis and very likely you’ll get 10 different treatment strategies. That’s because there are no standard treatments for juvenile arthritis. However, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) is looking to change that by developing consensus treatment plans for a number childhood rheumatic diseases.
CARRA was established in 2002 to create a network of pediatric rheumatologists across North America, providing infrastructure to collaborate more easily in large, multicenter studies, increasing the number of participants in studies and reducing the time it takes to achieve results. Today, the majority of all pediatric rheumatologists in the United States and Canada count themselves as members of CARRA, representing more than 92 institutions.
The Arthritis Foundation has supported CARRA from the start, providing funding for its development and ongoing funding for its administrative core and support for the CARRA registry.
“The Arthritis Foundation has been instrumental in providing funding to keep CARRA and its initiatives going. This support has been critically important,” says Carol A. Wallace, MD, professor of pediatrics, University of Washington School of Medicine and Seattle Children's Hospital and past chair of CARRA.
It was Dr. Wallace and the other leaders of CARRA who first brainstormed the idea of developing consensus treatment plans that could help physicians make treatment choices based on evidence rather than habit or beliefs. With funding from the American Recovery and Reinvestment Act of 2009, CARRA launched two initiatives: development of the consensus plans and the CARRA registry. “In order to collect meaningful data to provide the evidence of the effectiveness of one treatment compared to another one , we needed to have a starting point where patients are treated in a similar fashion with standardized collection of information,” says Dr. Wallace.
What Are Consensus Treatment Plans?
The consensus treatment plans are a ground-breaking effort, says Dr. Wallace. “It’s a huge change, a big shift in how we’ve done things to date in pediatric rheumatology.”
How things have been done to date is based on habit or each doctor’s individual experience, as no studies exist that have determined the best treatment for pediatric rheumatic diseases. Most doctors agree on the basics of treatment, for example, the use of corticosteroids and methotrexate as a first course of action for some types of rheumatic disease, but that is where consensus ends. How much? How often? What route? For how long? When to taper off? These are questions that could have a hundred different answers.
The consensus plans offer a limited number of treatments to choose from that have been developed by input from CARRA members through a rigorous consensus processes. Pediatric rheumatologists agree to choose the treatment plan most closely resembles what they would do and what they feel would be best for a specific patient. The clinician then follows the plan and collects data about how the patient responds and if there are problems with the treatment.
“By having pediatric rheumatologists utilize one of the consensus treatment plans for their patients, we can then compare the relative outcomes for three or four different treatment approaches instead of literally hundreds of different approaches, most with only minor differences from each other,” says Tim Beukelman, MD, associate professor of pediatrics in the Division of Pediatric Rheumatology at the University of Alabama at Birmingham School of Medicine, and vice chair of the CARRA Juvenile Idiopathic Arthritis (JIA) Committee.
“If we’re ever going to learn about the best way to treat any disease, we must standardize treatments and collect the information about the patients on these treatments,” says Yukiko Kimura, MD, a pediatric rheumatologist at Joseph M. Sanzari Children’s Hospital in Hackensack, N.J., and chair of the CARRA JIA committee and incoming vice chair of the CARRA Steering Committee.
Dr. Kimura points to the pediatric oncology community as a model, which has significantly increased survival rates of children with cancer by developing treatment standards, continually updating and retesting them.
“They standardized their treatments and got all the pediatric oncologists to use these treatments and collected the information,” she explains. “And gradually, they were able to understand how to fine tune the treatments and find the best treatments that result in the best outcomes for these kids. This is what’s needed in pediatric rheumatology.”
Right now, CARRA has published four groups of consensus treatment plans, one from each of its disease-specific committees.
Don’t Call Them ‘Guidelines’
Drs. Wallace, Beukelman and Kimura are quick to state that these consensus treatment plans are NOT guidelines. Guidelines are developed in very different and more formal way, relying solely on what’s been published in the medical journals.
The American College of Rheumatology (ACR) has guidelines for the treatment of JIA, but they are “incredibly general, not specific,” says Dr. Wallace.
That’s because there is no evidence yet, she adds. “What we are doing will inform the next iteration of those guidelines with evidence.”
The consensus treatment plans are called that “because they involved many pediatric rheumatologists in CARRA discussing, agreeing and coming to a consensus about how children with [arthritis] should be treated,” says Dr. Kimura.
The Consensus Process
Reaching consensus was no easy feat. CARRA has four disease-specific committees that participated in this effort: the JIA committee, the Juvenile Dermatomyositis (JDM) committee, the Systemic Lupus Erythematous (SLE) committee and the Scleroderma, Vasculitis and Rare Diseases (SVRD) committee. Each was tasked with developing a set of consensus treatment plans.
Once the groups chose which specific disease to focus on, the committees polled the 300+ CARRA members about their current treatment practices. The data were then compiled and served as the basis for discussion of committee members at the two-day, in-person 2010 CARRA meeting. In addition to the approximately 20 to 50 voting pediatric rheumatologist committee members, parents of children with JA and other lay members sat in on the discussions.
The in-person meetings involved a lot of discussion and compromise to establish three or four treatment plans that the members believed would be agreeable to all.
“We wanted the plans to be as well defined as possible so that they are easier to compare,” says Emily von Scheven, MD, chief, Division of Pediatric Rheumatology at the University of California, San Francisco, and chair of CARRA’s SLE committee. “But we wanted the treatment plans to look as close as possible to what people were doing out there so they’d be comfortable using them. And we wanted them to line up with the best available literature.”
A second survey was then employed to help hammer out any remaining issues. Once consensus was reached – 80 percent agreement within the committee – a final survey was sent to all CARRA members to determine if they would use the consensus treatment plans in their clinical practice.
In the end, each committee published their consensus treatment plans in Arthritis Care & Research in 2012. Each group of plans describes data to be collected, time points for data collection and corticosteroid taper plans. Data will be collected into the CARRA Registry. When sufficient numbers of patients have been treated with the treatment plans, comparisons between treatments will be made in terms of how quickly improvement and remission was achieved, how long it lasted and if patients experienced side effects from the medications. Following is a brief summary of each.
Treatment Plan Summaries
Systemic Juvenile Idiopathic Arthritis: The JIA committee chose to focus their first consensus treatment plan on systemic JIA. Making up just about 5 to 15 percent of all cases of JIA, systemic JIA may also be the most variable subset of JIA, which makes it all the more difficult to standardize its treatment. The consensus treatment plan presents four treatments: corticosteroids only, methotrexate, anakinra (Kineret) and tocillizumab (Actemra), all with or without corticosteroids.
Lupus Nephritis: The SLE group focused their consensus treatment plan specifically on the induction phase – or the first six months of treatment – of lupus nephritis, which is seen in about 80 percent of all children with SLE. The consensus plans present immunosuppressive therapy options of either daily oral mycophenolic acid (CellCept) or monthly intravenous cyclophosphamide (Cytoxan), as well as three options for use of corticosteroids.
Juvenile Dermatomyositis: The JDM committee provided three plans for the treatment of moderate juvenile dermatomyositis: IV methylprednisolone, methotrexate and predisone; IV methylprednisolone, methotrexate, prednisone and IV immunoglobulin; and finally, methotrexate and prednisone.
Juvenile Localized Scleroderma: The SVRD committee developed consensus treatment plans focusing on the first year of treatment of juvenile localized scleroderma. The plans include methotrexate alone; methotrexate and IV corticosteroids; and methotrexate plus a combination of oral and IV corticosteroids.
As a patient or a parent of a patient, you may never know that you are part of one of these treatment plans, and that is the point. If your pediatric rheumatologist thinks your child is a candidate for one of the protocols, they will likely follow it, but CARRA recognizes the many variables in pediatric rheumatic diseases and that sometimes circumstances dictate that your doctor follows another course of treatment.
“We’re not trying to take judgment away from physicians. We are trying to standardize treatments so they can be compared,” explains Dr. Wallace.
While the primary goal is to develop standards of care, an added benefit is that publication of these treatment plans may also reach doctors who see JA patients but aren’t pediatric rheumatologists and may not be sure of the most current treatments.
CARRA sees these consensus treatment plans as works in progress. As new treatments are introduced and evidence is collected, these plans will change and improve. The data collection on these treatment plans “will inform not only which treatment protocol is best, but which is safest and with the least side effects,” says Dr. Wallace.
“With time, our goal is to have the best treatment for each patient -- personalized care, which is where they are with childhood cancer,” she says. “Eventually, we will achieve that.”