| Sumario de la revisión comparativa de la efectividad de la AHRQ sobre los antireumáticos para niños que modifican la artritis idiopática juvenil |
Summary of AHRQ's Comparative Effectiveness Review of Disease-Modifying Antirheumatic Drugs for Children with Juvenile Idiopathic Arthritis.
McMahan R, Balfe LM, Greene L.
1300 Amerigroup Way, Amerigroup Corporation Virginia Beach, VA 23464, USA.rmcmah1@amerigroupcorp.com.
J Manag Care Pharm. 2012 Jan-Feb;18(1 Suppl B):1-16
Abstract
BACKGROUND: A systematic review on the comparative effectiveness of disease-modifying antirheumatic drugs (DMARDs) used to treat children with juvenile idiopathic arthritis (JIA) was published by the Agency for Health Care Research and Quality (AHRQ) in September 2011. Studies from 198 articles included in the review addressed the benefits and harms of DMARDs compared with conventional treatments and other DMARDs used to treat JIA. The review also incorporated studies comparing various clinical tools used for diagnosing JIA and measuring disease activity. Clinical outcome measures were analyzed to determine the most effective methods to measure disease state. The lack of current research for the treatment of JIA motivated AHRQ to contract with researchers to synthesize the available information with the intent of enabling health professionals to make evidence-based practice decisions for their patients. The review alsohighlights gaps in the research and areas that need to be addressed in the future. OBJECTIVES: 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.
http://ce.effectivehealthcare.ahrq.gov/programs/CER19/AHRQ-CER19-JIA.pdf
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| Antirreumáticos modificadores de la enfermedad en niños con artritis juvenil idiopática |
Disease-Modifying Antirheumatic Drugs (DMARDs) in Children With Juvenile Idiopathic Arthritis (JIA)
Editors
Kemper AR, Coeytaux R, Sanders GD, Van Mater H, Williams JW, Gray RN, Irvine RJ, Kendrick A.
Rockville (MD): Agency for Healthcare Research and Quality (US); 2011 Sep. Report No.: 11-EHC039-EF.
AHRQ Comparative Effectiveness Reviews.
Excerpt
OBJECTIVES: To summarize the benefits and harms of disease-modifying antirheumatic drugs (DMARDs) compared to conventional treatment (non-steroidal anti-inflammatory drugs [NSAIDs] and/or intra-articular corticosteroids) with or without methotrexate, and of the various DMARDs compared to one another, in children with juvenile idiopathic arthritis (JIA); and to describe selected tools commonly used to measure clinical outcomes associated with JIA. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews. Additional studies were identified from the review of reference lists. REVIEW METHODS: To evaluate efficacy, we included prospective trials that included a comparator and that lasted for at least 3 months. No comparator was required for reports of adverse events or of the clinical outcome measure tools. RESULTS: A total of 198 articles were included. There is some evidence that methotrexate is superior to conventional treatment (NSAIDs and/or intra-articular corticosteroids). Among children who have responded to a biologic DMARD, randomized discontinuation trials suggest that continued treatment decreases the risk of having a flare. Although these studies evaluated DMARDs with different mechanisms of action (abatacept, adalimumab, anakinra, etanercept, intravenous immunoglobulin, tocilizumab) and used varying comparators, followup periods, and descriptions of flare, the finding of a reduced risk of flare was precise and consistent. There are few direct comparisons of DMARDs, and insufficient evidence to determine if any specific drug or drug class has greater beneficial effects. Reported rates of adverse events are similar between DMARDs and placebo in nearly all published randomized controlled trials. This review identified 11 incident cases of cancer among several thousand children treated with one or more DMARD. The Childhood Health Assessment Questionnaire (CHAQ) was the most extensively evaluated instrument of those considered. While it demonstrated high reproducibility and internal consistency, it had only moderate correlations with indices of disease activity and quality of life, and poor to moderate responsiveness. CONCLUSIONS: Few data are available to evaluate the comparative effectiveness of either specific DMARDs or general classes of DMARDs. However, based on the overall number, quality, and consistency of studies, there is moderate strength of evidence to support that DMARDs improve symptoms associated with JIA. Limited data suggest that short-term risk of cancer is low. Future trials are needed to evaluate the effectiveness of DMARDs against both conventional therapy and other DMARDs across categories of JIA, and registries are needed to better understand the risks of these drugs.
http://www.ncbi.nlm.nih.gov/books/NBK65169/pdf/TOC.pdf |
| Artritis juvenil idiopática: Manejo y opciones de tratamiento |
Juvenile idiopathic arthritis: management and therapeutic options.
Ruth NM, Passo MH.
Ther Adv Musculoskelet Dis. 2012 Apr;4(2):99-110.
doi: 10.1177/1759720X11413630.
Abstract
THE GOALS OF TREATMENT FOR JUVENILE IDIOPATHIC ARTHRITIS (JIA) INCLUDE: suppression of inflammation, achievement of remission, relief of pain, maintenance of function and doing so with minimal toxicity. Important discoveries over the past 10-15 years have led to more targeted treatments for children with JIA. The International League of Associations for Rheumatology (ILAR) classification system for childhood arthritides, better assessment tools for clinical response, improved definitions of remission, new imaging techniques and evidence in gene expression profiling have all contributed to the development of more targeted treatments. Nonsteroidal anti-inflammatory agents still have a role in mild disease and intra-articular steroid injections continue to be used most commonly in patients with oligoarticular JIA. Disease-modifying agents such as methotrexate have demonstrated efficacy and safety; however, in many patients, the disease remains active despite this treatment. These children now receive more targeted treatment including the tumor necrosis factor alpha (TNFα) inhibitors, interleukin-1 blockade, interleukin-6 blockade, selective costimulation modulators and selective B-cell blockade. The biologic targeted therapies have changed the strategy in which we treat our children with JIA; however, there remains much to be learned about the long-term effects and safety of these medicines
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3383518/pdf/10.1177_1759720X11413630.pdf
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| Retos en el tratamiento de artritis juvenil idiopática con etanercept |
Challenges in the management of juvenile idiopathic arthritis with etanercept.
Pain CE, McCann LJ.
Alder Hey Children's NHS Foundation Trust, Eaton Road, Liverpool, UK.
Biologics. 2009;3:127-39. Epub 2009 Jul 13.
Abstract
Biologic agents have been designed with the help of immunological studies to target particular areas of the immune system which are thought to play a role in the pathogenesis of disease. Etanercept is a soluble anti-tumor necrosis factor alpha (TNF-alpha) agent licensed for the treatment of active poly-articular juvenile idiopathic arthritis (JIA) in children aged 4 to 17 years who have failed to respond to methotrexate alone, or who have been intolerant of methotrexate. The safety and efficacy of etanercept in this patient group has been established by one randomized controlled trial and several longitudinal studies. This, together with the fact that until recently etanercept was the only anti-TNF licensed in JIA, has made it the most common first choice biologic for many clinicians. However, there are still many unanswered questions about etanercept, including its efficacy and safety in different subtypes of JIA, in children under 4 years of age and in those with uveitis. There are still concerns about the long term safety of TNF antagonists in the pediatric age group and unanswered questions about increased risks of malignancy and infection. Although adult studies are useful to improve understanding of these risks, they are not a substitute for good quality pediatric research and follow-up studies. Adult trials often include greater numbers of patients. However, they evaluate a different population and drug behavior may vary in children due to differences in metabolism, growth and impact on a developing immune system. In addition, rheumatoid arthritis is a different disease than JIA. Clinicians need to carefully weigh up the risk benefit ratio of anti-TNF use in children with JIA and push for robust clinical trials to address the questions that remain unanswered. This article summarizes the evidence available for use of etanercept in children with JIA and highlights aspects of treatment in need of further research.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2726066/pdf/btt-3-127.pdf
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