martes, 18 de agosto de 2009

Juvenile Idiopathic Arthritis (JIA) // AHRQ Effective Health Care Program - Provide Comments




Comparative Effectiveness of disease-modifying anti-rheumatic drugs (DMARDs) in children with juvenile idiopathic arthritis (JIA)
Open for comment through 11 Sep 2009


Background
Overview

Juvenile Idiopathic Arthritis (JIA), formerly known as Juvenile Rheumatoid Arthritis (JRA), is the most common rheumatologic disease in childhood, with an overall prevalence of 70 to 400 per 100,000 children.1 JIA is an important cause of chronic disease in childhood, with a prevalence similar to type 1 diabetes mellitus.2 JIA consists of at least six subtypes with distinct yet overlapping clinical manifestations. These are:3

Systemic arthritis- The initial presentation includes fever, rash, and arthritis. One-quarter of patients may have severe destructive joint disease.
Oligoarthritis – Affects up to four joints in the first six months of the illness. May be persistent (i.e., no more than four joints) or extended (i.e., more than four joints after the first six months of illness). May be associated with the development of uveitis.
Polyarthritis – Affects five or more joints during the first six month of disease. Divided into rheumatoid factor (RF) negative and positive disease. RF-positive disease may be associated with more destructive joint disease.
Enthesitis-related arthritis – May also be associated with uveitis.
Psoriatic arthritis – May also be associated with uveitis.
Other – Arthritis of unknown cause for more than six weeks.
JIA can place a severe physical and psychological burden on affected children and be a major stressor to families. As with all chronic conditions in childhood, treatment may be enhanced by a multidisciplinary team to address these issues. There is no curative treatment for JIA. Until recently, treatment has focused on the use of non-steroidal anti-inflammatory drugs (e.g., ibuprofen, naproxen) and intra-articular injections of corticosteroids.4 Unfortunately, many patients will not respond to this first-line therapy.

Therapy with the so-called disease-modifying anti-rheumatic drugs (DMARDs) has become an increasingly important component of care. These drugs, which operate through a number of different mechanisms (see Table), share the common effect of limiting radiologic progression of disease.4 Although these drugs can dramatically improve the disease course, no evidence-based guidelines exist regarding the management of JIA with DMARDs. There are many unanswered questions about the safety and effectiveness of these drugs, especially for their long-term use in children.


Controversy and Uncertainty
A clear evidence-based synthesis of the evidence is needed to help clinicians provide care for children with JIA. This is especially important because there is a workforce shortage of pediatric rheumatologists,5 leading to treatment of children by adult-focused rheumatologists who may not have a comprehensive understanding of the evidence. Understanding when to use a DMARD is especially challenging because JIA is heterogeneous across the various subtypes. Furthermore, there are a large number of DMARDs that cannot simply be grouped by class. Failure with a drug in one particular class does not necessarily predict failure with another drug in the same class. Some children may even benefit from treatment with more than one DMARD at a time.

In order to assess the benefits or harms of any therapy, it is critical to have a comparison treatment. For many therapies, this is a placebo. However, for JIA the most appropriate comparator to judge the effectiveness of a DMARD or combination of DMARDs may be methotrexate. Methotrexate is a DMARD that has been found to be highly effective, and often is the first DMARD used in children with JIA.6 Methotrexate has also been available for much longer then the other DMARDs, so there is greater clinical experience with the drug and the drug is relatively inexpensive.

Another critical component to evaluating the effect of therapies is the measurement of their impact. Evaluating changes in JIA disease status can be challenging. Most studies use the ACR-30 scoring system, which evaluates the following domains: patient function, patient/parent assessment of well-being, physician assessment of overall disease activity, number of joints with active arthritis, number of joints with limited range of motion, and erythrocyte sedimentation rate (ESR). Improvement in any three of these domains by 30% and worsening in not more than one by 30% is considered to be improvement.7 Other disease scoring systems have been developed (e.g., the Juvenile Arthritis Disease Activity Score [JADAS]).8 The key informants identified three important concerns with existing scoring systems. First, these measures evaluate relative and not absolute changes in disease progression. However, standardized “absolute” measures may provide greater insight. Second, these instruments may not reflect the goals of treatment. For example, many providers would not consider a 30% improvement to be a clinically significant improvement. Even the ACR-70, which evaluates for a 70% improvement may not be enough. Finally, some key informants who are clinicians noted that having an instrument that could be rapidly used in daily practice would be more helpful in assessing the impact of DMARDs. Regardless of the measure, it is important to be able to measure clinically meaningful responses to therapy and to assess for remission.

Relevance

JIA is associated with significant morbidity and mortality. Affected individuals, their families, and clinicians are especially excited with the new DMARDs, which they believe may lead to more extensive resolution of symptoms for longer periods of time. Unfortunately, DMARDs are expensive and the risks of therapy are not clear. The disease experts we interviewed, including clinicians, a parent of a child with JIA, and a representative of a large health insurer, all underscored the need for a synthesis of the evidence to guide management. This is especially important because of workforce shortages in pediatric rheumatology. As a result, many adult-trained rheumatologists provide care for children. A clear summary of the evidence would help these other health care providers in making evidence-based decisions and likely lead to overall improvements in outcomes for children with JIA. Both the parent and the payer who served as key informants identified the importance of an unbiased assessment of the evidence. The experts also endorsed synthesizing available data to identify missing gaps in the evidence and to set a future agenda in JIA clinical research.


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