To (a) educate health care practitioners on the findings from AHRQ's 2011 comparative effectiveness review on DMARDs used to treat children with JIA, (b) apply review findings to make diagnosis and treatment decisions in clinical practice, and (c) recognize limitations and gaps n the current research relating to the comparative benefits and harms of DMARDs for treatment of JIA.
SUMMARY: JIA is a chronic inflammatory disease affecting approximately 300,000 children and adolescents in the United States.1 Initially manifesting with
inflammation, swelling,
pain, and stiffness of the joints, the disease as no apparent or known cause. JIA is a clinical diagnosis based on several actors including the number of affected joints and the involvement of other tissues (e.g., the skin and lymphoid tissues), and JIA has 7 categories: systemic-onset
arthritis,
oligoarthritis,
rheumatoid-factor positive
polyarthritis,
rheumatoid-factor negative polyarthritis, enthesitis-related
arthritis, psoriatic arthritis, and undifferentiated
arthritis.2 Complete remission and resolution of disease activity are the ultimate treatment goals; however, there is no present cure. Inhibition of
inflammation, prevention of joint damage, and promotion of a high level of functioning are the immediate goals of treatment. Even with treatment, patients with JIA continue to experience disease activity, joint destruction, suboptimal function, and impaired quality of life, all of which extend into adulthood.3 JIA can be severely debilitating and places a heavy physical and psychological burden on children and families affected by the disease.
Methotrexate is a nonbiologic
DMARD with an unknown mechanism of action.
Methotrexate has been used for so long in the treatment of JIA that it is frequently considered a part of conventional treatment; the evidence shows that
methotrexate is superior to conventional treatment with NSAIDsand/or intra-articular
corticosteroids. The introduction of newer
biologic DMARDs has spawned optimism that treatment will increasingly lead to improved outcomes for JIA, but the evidence is insufficient to support superiority over
methotrexate. There is moderate evidence to support the claim that continued treatment from 4 months to 2 years with a
biologic DMARD in children who have responded to a
biologic DMARD decreases the risk of a flare. However, the safety of
biologic DMARDs for long-term use has not been determined and may be associated with the developmentof
cancer. The association between
tumor necrosis factor (
TNF) alpha inhibitors and potential increased risk of
lymphoma caused the U.S. Food and Drug Administration (FDA) to place boxed warning labels on
biologic DMARDs including etancercept,
infliximab, and
adalimumab. The effectiveness of the DMARDs appears to vary among categories of JIA and the treatment history of individual patients. Except for
methotrexate, there is insufficient evidence to support selection of a specific
drug or
drug class over another in the treatment of JIA. The AHRQ review examines the scientific literature on DMARDs used in children with JIA in an effort to synthesize what is known about the subject, and the comprehensive review identifies important research gaps in the literature that need to be addressed. Only 8 studies (in 9 publications) were rated "good quality" by the AHRQ investigators.