الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Rheumatoid arthritis is a systemic autoimmune disease characterized by chronic inflammation of the ýsynovial membrane resulting in joint destruction and disability. The clinical course of RA varies individually from mild joint symptoms to severe bone damage with loss of joint function. Despite optimum ýsuppression of disease activity with DMARD’s such as MTX and somewhat prevention of disease ýprogression and joint damage, there is still some patients with aggressive disease continue to experience ýdisease progression with radiological evidence of erosive damage within 2 years of onset of disease. This ýleads to considerable functional disability within 10 years resulting in major economic and social burden. ýThe inflammatory process in RA is initiated when T-cell is activated. This activation leads to chain of ýevents resulting in recruitment of monocytes and macrophages and secretion of proinflammatory cytokines ýparticularly TNF-? into synovial cavity. TNF-? is a multipotent cytokine, it induces production of other ýinflammatory cytokines s and chemokines such as IL8. In addition, TNF-? causes tissue destruction by ýpromoting release of matrix metalloproteinases (MMPs), increases the breakdown of proteoglycans in the ýcartilage and potentiates osteoclast differentiation and activation. There is now abundant evidence that ýTNF inhibition dramatically improves patient outcomes in RA. Three TNF-? blockers are available: ýEtanercept, Infliximab and Adalimumab. All of them have shown rather similar efficacy. They inhibit the ýinflammatory cascade by binding to TNF, preventing it from binding to receptors on nearby cells and thus ýpreventing the destructive joint lesion and the subsequent results. TNF-? blockers are remarkably effective ýin reducing disease activity, so that disease remission is now an achievable goal. Furthermore, TNF-? ýblockers can slow or stop the joint destruction, thereby significantly improving joint function and quality ýof life. Although each drug is designed to neutralize TNF, differences in these agents composition, ýmethods of administration and adverse effects have important implications for patients. These differences ýgive patients treatment options, if one drug is not effective, another one may provide better results. ýAlthough the TNF-? blockers are well tolerated, there is a number of common side effects including minor ýinfusion reactions such as rash, nausea and headache. TNF- α blockers should be used with caution in ýpatients with severe infection. There is also increased risk of tuberculosis and other granulomatous disease. ýIn addition, formation of anti- infliximab antibodies may occur if the body reacts to drug non human ýsequences as foreign proteins and the risk of drug-induced lupus is relatively low and has been reversed ýwith discontinuation of therapy. Finally, the risk of malignancy remains a concern with the long term use of TNF- α blockers. An increased risk of lymphomas has been reported in patients treated with TNF- α blockers.