الفهرس 
MethotrexateOnly 14 pages are availabe for public view
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Abstract
The goals of treatment of pediatric rheumatic diseases include suppression of inflammation with achievement of remission, relief of pain, maintenance of function, and minimizing toxicity of the drugs. Treatment with the class of agents known as disease-modifying antirheumatic drugs (DMARDs) has become an increasingly important component of care because these drugs appear to lead to better disease control, with higher numbers of children achieving remission, and fewer children suffering long-term joint damage. DMARDs interfere with the production and/or function of immune cells that cause joint inflammation and are typically classified as either biologic drugs, which are created by biologic processes, or non-biologic drugs, which are manufactured chemically. In general, the older, ,synthetic ,non-biologic DMARDs include the following most commonly used drugs: methotrexate, leflunomide , antimalarials ,sulfasalazine cyclophosphamide, mycophenolate mofetil, , azathioprine, cyclosporine and tacrolimus .
Methotrexate is the most commonly used agent in this class, and it is effective ,cost-effective and comparatively well tolerated .It’s considered one of the safest DMARDs. The evidence shows that methotrexate is superior to conventional treatment with NSAIDs and/or intra-articular corticosteroids in children with JIA. The role of individual drug therapy in the treatment of each systemic rheumatic disease varies widely.(Table 5)
Newer ,biologic DMARDs include TNF-α inhibitors (etanercept, infliximab, adalimumab, golimumab, and certolizumab), T-cell/B-cell coactivation signal inhibitors(abatacept),IL-1 antagonists (anakinra), anti–B-cell therapy (rituximab), IL-6 antagonist (tocilizumab) and intravenous immunoglobulins. The use of biologic DMARDs for the treatment of autoimmune and rheumatologic diseases is rapidly expanding, owing to the good efficacy and short term safety profiles of these drugs, and the better understanding of the initial targets of altered immune regulation and activity in various diseases. Although some of the biologic therapies have been found to be useful in more than one disease, others are specific for a single disease. (Table 5) Research is ongoing to identify other molecular targets.
Although there is significant optimism that treatment with the newer biologic DMARDs may increasingly lead to long-term disease remission, there are many unanswered questions about the safety of these drugs, especially for long-term use in children. TNF-α inhibitors has a potential increased risk of infection and malignancy, in particular lymphoma.
Oral administration, lower cost and greater prescriber familiarity support the use of synthetic DMARDs as a first-line strategy especially in RA and JIA . Biologic DMARDs, most often in combination with synthetic DMARDs, are generally reserved for the treatment of patients with moderate to severe disease, who have had an inadequate response or have developed toxicities to synthetic DMARDs.
The search continues for biomarkers and molecular networks that can help us better understand the variable response to targeted therapy. Today, the key challenge facing rheumatologists is how best to integrate the advanced therapies into daily practice. A clear synthesis of the available evidence is needed, to help clinicians provide care for children and to identify the important gaps in the scientific literature.
Table 5: DMARDs usage by disease.
AS, ankylosing spondylitis; Beh, Behc¸et disease; JIA, juvenile idiopathic arthritis; PM/DM, poly- and dermatomyositis; PMR, polymyalgia rheumatica; PsA, psoriatic arthritis; RA, rheumatoid arthritis; Sar, sarcoidosis; SLE, systemic lupus erythematosus; SjS, Sjo¨ gren syndrome; SSc, systemic sclerosis; Vasc, vasculitis
types; X, FDA-approved use; (ol), off-label use.