New treatment guidelines strongly endorse use of biologic agents for many children with arthritis refractory to methotrexate


The American College of Rheumatology has developed new guidelines for starting and monitoring treatments for children with juvenile idiopathic arthritis.

Key Points

Fueled by major changes over the last decade in the treatment of juvenile idiopathic arthritis (JIA), including the introduction of biologic therapeutic agents, the American College of Rheumatology (ACR) has developed new guidelines for starting and monitoring treatments for children with JIA. These are the first JIA guidelines endorsed by the ACR, with the goal of broad acceptance within the rheumatology community.

The research team, led by Timothy Beukelman, MD, MSCE, an ACR member, and assistant professor of pediatrics in the division of pediatric rheumatology at the University of Alabama at Birmingham, developed the guidelines using established processes from the Research and Development/University of California at Los Angeles (RAND/UCLA) Appropriateness Method. The method defines appropriate patient care by combining the best available scientific evidence with the collective judgment of experts.

The guidelines focus on the initiation and safety monitoring of multiple medications used in the treatment of JIA, including:

"The most recent classification of JIA uses 6 distinct categories. However, the treatment of JIA is not currently influenced by some of the distinct categories of JIA. For example, there are not specific therapies directed at psoriatic arthritis as opposed to oligoarthritis or RF [Rheumatoid factor]-negative polyarthritis," he told Formulary.

"Accordingly, we developed JIA 'treatment groups' for the recommendations based on important phenotypic differences in JIA. The 5 treatment groups are history of arthritis of 4 or fewer joints, history of arthritis of 5 or more joints, active sacroiliac arthritis, systemic arthritis with active systemic features, and systemic arthritis with active arthritis."

The treatment of JIA has changed dramatically over the last decade, Dr Beukelman explained. "The ACR recommendations provide evidence and consensus-based guidance that reflects the current state of the field. These recommendations endorse the use of biologic therapeutic agents for children with JIA whose arthritis remains active despite treatment with methotrexate. These recommendations are not intended to be used to determine insurance coverage policies, but my personal hope is that the recommendations will result in increased access to appropriate treatment."

The most notable recommendations regarding the use of biologic agents include the initiation of TNF-α inhibitors for children with a history of arthritis of 4 or fewer joints if significant arthritis proves refractory to methotrexate.

In addition, Dr Beukelman continued, "for children with a history of arthritis of 5 or more joints, the initiation of TNF-α inhibitors is recommended for essentially all patients with any active arthritis following an adequate trial of methotrexate. Finally, for children with systemic arthritis who require a steroid-sparing agent because of active fever, initiation of anakinra is recommended," he said.

In the development of the recommendations, Dr Beukelman and the research team, which included clinicians, researchers, and a patient advocate, performed a systematic review of the literature that identified more than 200 studies of the treatment of JIA. "These studies were abstracted and compiled into an evidence report that was presented to our voting panel," Dr Beukelman explained. "We also evaluated more than 1,500 clinical scenarios that captured the complexity of treatment decisions in JIA, including the JIA treatment group, disease activity, presence of features of poor prognosis, and current medications. The voting panel then considered the scenarios based on the published literature or their own expert opinions when sufficient evidence was not available."

It is estimated that 1 child in every 1,000 will develop a rheumatic disease. Nearly 300,000 American children suffer from JIA, which begins before patients reach aged 16 and may involve chronic inflammation of 1 or many joints. JIA often persists into adulthood and can cause long-term coexisting conditions and disability.


Beukelman T, Patkar NM, Saag KG, et al. 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features. Arthrit Care Rs. 2011;63:465–482.

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