Abstract
Targeted therapeutic agents have changed the landscape of therapy in rheumatoid arthritis (RA). They have also provided valuable insights into the utility of animal models for development of targeted therapies, clinical trial design, pharmacodynamics, immunobiology and key pathogenic elements of disease. Studies of chimeric anti-CD4 monoclonal antibodies in RA demonstrated the need for pre-clinical studies to more closely approximate the human therapeutic paradigm as well as the importance of synovium as an appropriate pharmacodynamic window to predict efficacy and adverse side effects of the agents. Targeted therapies have been instructive in discerning the importance of TNF, IL-1, IL-6, IL-15 and RANKL in the pathological process themselves, such as the uncoupling of inflammation and structural damage. Current trends in the use of targeted therapeutics include aggressive earlier use, combination with methotrexate, use in moderate rather than severe disease, tight control as well as induration and maintenance regimes. Despite therapeutic advances with target therapies a number of unmet needs exist, including a low remission rate, cost and inadequate access as well as the lack of biomarkers to predict response and safety concerns. Despite this, target therapies have revolutionized the treatment of RA. In addition to having a substantial effect on clinical outcomes, a number of valuable lessons have been learned.
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Keystone, E.C. (2009). Perspectives in targeted therapy. In: Tak, PP. (eds) New Therapeutic Targets in Rheumatoid Arthritis. Progress in Inflammation Research. Birkhäuser Basel. https://doi.org/10.1007/978-3-7643-8238-4_12
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