First ACR Advice for Juvenile Idiopathic Arthritis Treatment

Janis C. Kelly

April 04, 2011

April 4, 2011 — The American College of Rheumatology (ACR) discusses treatment options for juvenile idiopathic arthritis (JIA) and puts forth a set of recommendations intended to help clinicians navigate the data related to initiating and monitoring drug treatment. The recommendations appear in the April issue of Arthritis Care & Research and were endorsed by the Arthritis Foundation.

The review panel, led by Timothy Beukelman, MD, from the University of Alabama at Birmingham, was cautious in analyzing data and emphatic in noting the limitations of the resulting paper.

"The products of this project are termed 'recommendations' rather than guidelines in order to reflect their nonprescriptive nature. They are meant to function as a reference and do not serve as a substitute for individualized patient assessment and clinical decision making.... Importantly, these recommendations are not intended to limit health care coverage for children with JIA," the authors write.

The recommendations focus on the initiation and safety monitoring of multiple medications used in the treatment of JIA, including nonsteroidal anti-inflammatory drugs, intraarticular glucocorticoid injections, nonbiologic disease-modifying antirheumatic drugs such as methotrexate, biologic disease-modifying antirheumatic drugs (eg, abatacept, anakinra, and tumor necrosis factor α [TNF-α] inhibitors such as etanercept, adalimumab, and infliximab), and systemic glucocorticoids.

The analysis did not include the economic costs of treatment. It also did not include canakinumab, rilonacept, or tocilizumab, which were not widely available at the time of the literature search.

The recommendations were based on clinical scenarios derived from a systematic literature review and assessed using the RAND/UCLA Appropriateness Method for determining when the benefits of treatment outweigh the risks.

The research team — which included clinicians, researchers, and a patient advocate with experience and expertise in JIA — reviewed more than 200 studies related to JIA treatment and evaluated more than 1500 clinical scenarios that captured a broad range of medical decisions that are made in the care of JIA patients.

In place of the International League of Associations for Rheumatology 6-category JIA classification system, the panel used treatment groups, with the goal of facilitating clinical decision-making. The 5 treatment groups were:

  • history of arthritis with 4 or fewer joints,

  • history of arthritis with 5 or more joints,

  • active sacroiliac arthritis,

  • systemic arthritis with active systemic features (and without active arthritis), and

  • systemic arthritis with active arthritis (and without active systemic features).

Dr. Beukelman told Medscape Medical News, "Our goal was to provide evidence and consensus-based guidance that reflects the current state of the field and is useful to clinicians of all levels of experience with the treatment of JIA. Because the recommendations were developed using a rigorous methodology and are as evidence-based as possible, most of the recommendations should not be truly surprising to rheumatologists who frequently care for children with arthritis. However, some rheumatologists who treat children less frequently may be surprised by some of the recommendations, such as the use of biologic agents relatively early in the disease course."

The recommendations include:

  • use of glucocorticoid joint injections (triamcinolone hexacetonide) for active arthritis, regardless of concurrent therapy or JIA treatment group;

  • beginning treatment with TNF-α inhibitors in children with a history of arthritis in 4 or fewer joints and significant active arthritis despite 3 to 6 months of methotrexate;

  • beginning treatment with TNF-α inhibitors in children with a history of arthritis in 5 or more joints and any active arthritis after 3 to 6 months of methotrexate; and

  • beginning treatment with anakinra in children with systemic arthritis and active fever whose treatment requires a second medication in addition to systemic glucocorticoids.

Experts Debate the Value of the ACR Recommendations for JIA

Thomas J. A. Lehman, MD, who reviewed the recommendations for Medscape Medical News, questioned several points, most notably the use of methotrexate before initiating anti-TNF treatment.

Dr. Lehman said, "Recommendations based on Delphi analysis of hypothetical cases always suffer from a lack of recognition of the individual child's and family's preferences and circumstances. While these recommendations are important, in that they emphasize the need for more aggressive therapy of childhood disease, the 'recipe' approach is not always useful in clinical practice.

"There are still too many different diseases being lumped together under the heading of JIA for an analysis of this type to be universally applied. In addition, it is very likely that the recommendation for the use of methotrexate before an anti-TNF will unnecessarily delay the institution of anti-TNF therapy in many children. Why should children be allowed to fail methotrexate for 3 or 6 months with additional damage accumulating before being advanced to more efficacious therapy?"

Dr. Lehman is chief of pediatric rheumatology at the Hospital for Special Surgery and professor of clinical pediatrics at Weill Cornell Medical College in New York City.

Dr. Beukelman said, "There are many unanswered questions in the treatment of JIA. Personally, in the future I am eager to see comparative studies of the long-term benefits and risks of early initiation of biologic agents and studies of the appropriate management of patients who achieve a state of inactive disease while receiving therapy. I believe the refinement and widespread implementation of continuous disease activity scores in clinical practice would greatly increase our ability to compare patients across treatment centers and increase our knowledge."

Ongoing discussions about healthcare costs cast a bit of a shadow over the panel deliberations, Dr. Beukelman said. "These recommendations are explicitly not intended to be used to determine healthcare coverage policies for children with arthritis. However, insurance companies are free to do as they please to best serve their interests, making it difficult to speculate about the potential impact of the ACR recommendations. Our hope is that the recommendations will result in increased access to appropriate treatment for children with arthritis."

Dr. Lehman worried that the recommendations might have the unintended consequence of jeopardizing care for JIA patients.

"These recommendations do not take the place of having a child seen by an experienced pediatric rheumatologist, yet an adult rheumatologist with these in hand might no longer feel the need to refer. The proper care of children with arthritis is referral to an experienced pediatric rheumatologist, and experienced physicians treat individual patients, rather than following recipes," Dr. Lehman said.

The study was supported by the ACR, a grant from the Agency of Healthcare Research and Quality to the University of Alabama at Birmingham Deep South Musculoskeletal Center for Education and Research on Therapeutics, and a grant from the National Institutes of Health to the University of Alabama at Birmingham Center for Clinical and Translational Science. Dr. Beukelman has disclosed no relevant financial relationships. Other members of the ACR panel have received consultant fees, speaking fees, and/or honoraria from Merck, Lilly, Novartis, P&G, Aventis, Genentech, Takeda, AstraZeneca, Horizon, Bristol-Myers Squibb, and Roche. Dr. Lehman has disclosed no relevant financial relationships.

Arthr Care Res. 2011;63:465-482.

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