快樂小藥師 Im pharmacist nichts glücklich

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 (NSAIDs), 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 (ILAR) 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. Full text

Related Link
The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) provides an online fact sheet for parents and children affected with Juvenile Arthritis.

Clinical Context

JIA is defined by ILAR as a type of arthritis of unknown cause of at least 6 weeks, with other known conditions excluded. It is one of the common chronic conditions of childhood, with a prevalence of 1 in 1000. It can persist into adulthood with morbidities, yet no validated guidelines exist for its treatment.

This is a set of recommendations developed by the ACR for 5 categories of JIA endorsed by the Arthritis Foundation. These recommendations are to guide clinicians in management of the condition and are intended to be nonprescriptive.

Study Highlights

• The recommendations cover the indications for safety monitoring for the use of NSAIDs, intraarticular glucocorticoid injections, nonbiologic disease-modifying antirheumatic drugs, biologic disease-modifying antirheumatic drugs, and systemic glucocorticoids.
• A systematic review of the literature was performed by members of the Core Task Force and the Core Expert Panel.
• Only the most relevant and frequently used agents from each class were considered, and those agents not widely available were excluded.
• Although the ILAR divides JIA into 6 categories, the Core Expert Panel used 5 treatment categories for this report.
• For each category, features of poor prognosis are defined by clinical and radiographic features and disease activity levels.
• Recommendations for reduction of therapy are not addressed.
• For each treatment group, if criteria for escalation based on disease activity, features of poor prognosis, and duration of therapy are not met, then current therapy is recommended with adjunct NSAIDs or glucocorticoid joint injections.
• The first category, "history of arthritis of 4 or fewer joints" includes patients of ILAR categories of persistent oligoarthritis, psoriatic arthritis, enthesitis-related arthritis, and undifferentiated arthritis. These patients have had arthritis of 4 or fewer joints total and did not have systemic disease.
  • Treatment recommendations begin with NSAID monotherapy for low disease activity and escalate to glucocorticoid joint injections for low, moderate, or high disease activity with poor prognosis.
  • After repeated joint injections, the next step of treatment is methotrexate followed by a TNF-α inhibitor.
  • NSAIDs can be added or continued as needed for every escalation of treatment.
  • Initiation of abatacept is uncertain before use of TNF-α inhibitor.
• The second treatment group is "history of arthritis of 5 or more joints" and includes ILAR categories of extended oligoarthritis, rheumatoid factor (RF)–negative polyarthritis, RF-positive polyarthritis, psoriatic arthritis, enthesitis-related arthritis, and undifferentiated arthritis. Patients in these categories have had active arthritis in 5 or more joints in total in their history.
  • After use of NSAIDs, treatment consists of methotrexate with adjunct NSAIDs or joint injection as indicated.
  • After 3 to 6 months of methotrexate, a TNF-α inhibitor is used with NSAIDs or joint injection as needed, with a second TNF-α inhibitor or abatacept in those with moderate to high disease activity as the final option.
• The third group, "active sacroiliac arthritis," includes all patients with clinical and imaging evidence for active sacroiliac arthritis, primarily in the ILAR categories of enthesitis-related arthritis and psoriatic arthritis.
  • In this group, a TNF-α inhibitor is recommended after methotrexate or failure of sulfasalazine, especially in patients with high disease activity and poor prognostic features.
• The fourth group consists of "systemic arthritis with active systemic features (and without active arthritis)." This group includes patients in all of the ILAR categories who have had systemic arthritis and active fever of JIA but have not had active arthritis.
  • An example is a patient whose arthritis resolved spontaneously with NSAIDs but whose fever persisted.
  • Treatment would begin with NSAIDs, followed by systemic glucocorticoids, anakinra, and adjunct NSAIDs or glucocorticoids as needed.
• The fifth category is "systemic arthritis with active arthritis (and without active systemic features)." This group includes ILAR categories of patients with systemic arthritis and active arthritis but no active systemic features.
  • Treatment begins with methotrexate after a trial of NSAIDs, followed by a TNF-α inhibitor or anakinra, with adjunct joint injection or NSAIDs as needed.
  • If the TNF-α inhibitor fails, then abatacept may be tried in those with moderate and high disease activity.
• Recommendations for medication monitoring are given for each category of medication recommended.

Clinical Implications

• A total of 5 treatment categories of JIA are recognized by the ACR. Treatment escalation is provided for each category, depending on treatment history, disease activity, and poor prognostic features.
• For each set of recommendations, adjunct joint injections and NSAIDs are recommended as needed, and escalation criteria have to be met for treatment escalation.