ACR JIA Recommendations Updated: Use First-Line Anakinra

Janis C. Kelly

September 25, 2013

New treatment options and rapid progress in understanding of juvenile idiopathic arthritis (JIA) pathophysiology led the American College of Rheumatology (ACR) to update its 2011 recommendations on the treatment of systemic JIA. The update, published online September 24 and in the October issues of Arthritis & Rheumatism and Arthritis Care & Research , includes new guidance on use of anakinra, canakinumab, and tocilizumab in systemic JIA, as well as recommended treatment pathways for both initial and continued disease.

The guidelines team was led by Sarah Ringold, MD, from the Seattle Children's Hospital in Washington, and Pamela Weiss, MD, from Children's Hospital of Philadelphia in Pennsylvania.

"In the updated recommendations, we examine several medications not considered in the 2011 recommendations, including the anti-[interleukin (IL)]-1 agents canakinumab and rilonacept and the anti-IL-6 agent tocilizumab. Three phenotypes of systemic JIA, including systemic JIA with features of macrophage activation syndrome (MAS), are specifically addressed in the updated recommendations vs 1 phenotype in the prior guidelines. Lastly, we updated recommendations for repeat tuberculosis screening in children," coauthor Pamela Weiss, MD, from the Children's Hospital of Philadelphia, told Medscape Medical News.

"For those pediatric rheumatologists with a firm knowledge of the supporting literature on the treatment of systemic JIA, these recommendations may or may not affect clinical practice. For pediatric rheumatologists less familiar with the literature, for adult rheumatologists caring for children, and for general pediatricians without access to pediatric rheumatology colleagues, these guidelines should be a valuable resource for providing recommendations for the most common systemic JIA phenotypes encountered," Dr. Weiss said.

According to the authors, "The specific aims of the project were to 1) update the 2011 ACR recommendations regarding indications for starting nonbiologic [disease-modifying antirheumatic drugs (DMARDs)] and biologic DMARDs for systemic JIA and indications for switching between nonbiologic DMARDs and biologic DMARDs for systemic JIA; 2) incorporate the use of anti–IL-1 and anti–IL-6 therapies into the ACR recommendations for the treatment of systemic JIA; and 3) develop treatment recommendations for patients with the following 3 general systemic JIA phenotypes: significant systemic features and varying degrees of synovitis, significant arthritis and no significant systemic features, and features concerning for MAS."

Systemic features include fever, evanescent rash, lymphadenopathy, hepatomegaly, splenomegaly and/or serositis. MAS was defined as any combination of persistent fever, cytopenias or falling cell line counts, falling ESR, hypertriglyceridemia, hypofibrinogenemia, hemophagocytosis, transaminitis, coagulopathy, organomegaly, low natural killer cell activity, hyperferritinemia, or central nervous system dysfunction.

Update Sets Treatment Pathways for 3 JIA Phenotypes

For systemic JIA with active systemic features and varying degrees of synovitis., the ACR panel considered treatment for patients with a physician global assessment of less than 5 or 5 or higher on a 10-point scale and joint counts of 0, 1 to 4, or more than 4. Recommended initial therapy was anakinra with systemic glucocorticoids in most cases.

For systemic JIA without active systemic features and with varying degrees of active synovitis, the panel was asked to rate the appropriateness of treatments for patients with active joint counts of 4 or less or more than 4. The recommended initial treatments were methotrexate or leflunomide for an active joint count higher than 4, with change to abatacept, anakinra, a tumor necrosis factor alpha inhibitor, or tocilizumab if disease activity continued after 3 months of methotrexate or leflunomide. Nonsteroidal antiinflammatory drug monotherapy or intraarticular glucocorticoid injections were recommended as initial treatment for patients with 4 or fewer active joints.

For systemic JIA with features suggesting MAS, the authors note that the mortality rate for children hospitalized with systemic JIA and MAS is an estimated 6% and may be even higher. Recommendations for initial treatment included anakinra, a calcineurin inhibitor, or systemic glucocorticoid monotherapy for up to 2 weeks.

Front-line Biologics for Children With JIA May Surprise Some Clinicians

Pediatric rheumatologist Karen B. Onel, MD, told Medscape Medical News that the systemic JIA update codifies what is already standard-of-care for pediatric rheumatologists but may represent a change in approach for adult rheumatologists who only occasionally treat pediatric patients, as well as for third-party reimbursers.

"The guidelines provide a snapshot of best treatment for systemic JIA today and will be really useful, especially for clinicians who are not accustomed to treating children with first-line biological therapy," said Dr. Onel, who is associate professor of pediatrics in the Division of Rheumatology at the University of Chicago's Center for Advanced Medicine and at Corner Children's Hospital, Chicago, Illinois.

Dr. Onel stressed that systemic JIA is a very different disease from polyarticular JIA and requires a different treatment approach. "These are very sick children, and first-line therapy is a biologic such as anakinra because they need aggressive treatment right away. This is a bad disease and otherwise will have bad outcomes. The guideline update lays out a treatment pathway, and we need to move through it pretty quickly. If anakinra has not brought symptoms under control after 1 month, move to the next step," Dr. Onel said.

Recommendations May Reduce Number of Tuberculosis Tests in Children With JIA

The updated recommendations also include guidance for tuberculosis (TB) screening of children being treated with biologics. Testing for latent TB before beginning biologicals is standard of care, but repeat screening is recommended only for patients with an initial negative TB test whose risk of TB has changed to moderate or high, depending on regional infectious disease guidelines.

"The need for repeated TB screening really depends on where you practice," Dr. Onel said. "Patients or their parent should be questioned once a year about TB risk factors, but routine yearly TB tests are not recommended for those whose risk remains negligible."

This work was funded by the American College of Rheumatology, the National Institute of Arthritis and Musculoskeletal and Skin Disease, and the Agency for Healthcare Research and Quality. Dr. Ringold and Dr. Weiss have disclosed no relevant financial relationships. Other study authors reported consulting fees, speaking fees, and/or honoraria from Genentech, McKesson Health Solutions, Novartis, Janssen, and Hoffman-LaRoche. Dr. Onel has disclosed no relevant financial relationships.

Arthritis Rheum. 2013;65:2499-2512. Full text

Arthritis Care Res. 2013;65:1551-1563. Abstract

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