oa Editorial [Hot topic: General Aspects of Biologic Agents in Rheumatology (Guest Editor: Omer Faruk Sendur)]

Advances in understanding of the pathology of immune based disorders and especially new developments in the field of biotechnology, have triggered great interest in the development of new therapies for inflammatory rheumatic diseases. Subsequently the treatment spectrum of rheumatic inflammatory diseases have increased by quantity and variety in the last years. Earlier uses of traditional disease modifying antirheumatic drugs, along with the arrival of newer therapies including the biologic agents, have provided better long term outcomes for patients suffering from these illnesses. In recent years our better understanding of these disorders has shifted treatment strategy from a more conservative approach to a much more aggressive one, especially in treatment of rheumatoid arthritis. Although conventional treatment modalities remain the mainstay and are sufficient in many of patients today we have clearly entered the “biologic treatment” era in the field of management of rheumatic diseases [1]. The term of biologic therapy have arised as term to define therapeutic agents with biologic properties and refers to treatment that boosts or restores the ability of the immune system to fight with inflammatory process which seen in arthritis. Efforts to develop new biologic agents for treating patients with refractory rheumatoid arthritis have been accelerated in 90's. Research focused on understanding the pathogenesis of rheumatoid arthritis has resulted in revolution therapeutic advances through the targeting cytokine mediators in the inflammatory cascade from late 1990s to 2005. Finally today a lot of biological agents have been approved for management of a various inflammatory arthritis by FDA [2]. New biological agents developed for treatment of inflammatory joint diseases in the last decade have proven to be effective for a majority of patients unresponsive to traditional therapies. As pathogenesis of rheumatoid arthritis becomes clear the proinflammatory role of cytokines, the involvement of different cell types and their surface molecules, provides the rationale for the development of highly specific therapeutics by targeting these molecules. These can be achieved by; first, the cytokines of interest may be prevented from binding to its cell surface receptors by soluble receptors, natural antagonists, or monoclonal antibodies. Second, anti-inflammatory cytokines such as IL-4, IL-10 or IL-13, can inhibit the production or expression of inflammatory cytokines. Third, biological agents targeted against differentiation or functionally associated cell surface antigens can lead to either elimination of the targeted cells or interference with cell function [3]. Most of the approved biologics explore the first strategy mentioned above; they impair the binding of proinflammatory cytokines to their receptors. Among them, tumor necrosis factor (TNF) and IL-1 have been the most intensively investigated. These biological agents are mostly product of recombinant DNA technology, also known as bioengineered replicas of human proteins, which should be administered by subcutaneous injection or intravenous infusion. These agents has quicker onset of action than traditional disease modifying anti-rheumatic drugs , produced rapid and sustained therapeutic responses, and did not require regular laboratory monitoring [2]. TNF-α antagonist are highly effective in the treatment of many chronic inflammatory diseases, as demonstrated in several randomized clinical trials, showing clinical and radiological improvement in treated patients. The different mechanism of action between monoclonal antibodies (infliximab and adalimumab) and soluble receptor (etanercept) for TNF-α is proved by the results of the switching in case of inefficacy and adverse events. IL-1 is a proinflammatory cytokine that shares many properties similar with TNF- α and is associated with the characteristic inflammatory joint destruction of rheumatoid arthritis (RA). Anakinra is a recombinant form of IL-1 receptor antagonist, a naturally occurring IL-1 receptor ligand that competes with IL-1 for binding to cell surface-bound IL-1 receptor, but does not induce intracellular signaling.In many controlled studies has been shown that Anakinra reduce signs and symptoms of synovitis and slow radiographic progression of joint damage in RA [3]. The development of new agents and widespread use of existing agents continues to be a highly active area of investigation among the rheumatic diseases. In the future, improved versions of existing drugs will become available. Already anti TNF- .. preparations that are given as monthly subcutaneous injections are currently being developed. Other targets for therapy such as IL6, CD22, CD40-CD40L, lymphostat B and many others are under study. Currently there is no doubt of improving outcomes for patients with rheumatic diseases by biological agents. As is known most of the clinical studies carried out with biologics are designed in RA patients. Biologics bring new hope to those patients that do not respond adequately to traditional DMARDs in the treatment of RA signs and symptoms and beyond that also ameliorate radiographic progression. But how to establish of these agents most safe, efficient, cost-effective means of delivering is needed to be explicated in well designed trials [4]. “Fear of the unknown should not preclude progress, but caution must be essential” I hope in this issue the reviews will guide the readers the appropriate way of use biologics and answer of most questions of curiosity about these new agents in treatment fields of rheumatology. Many thanks to all authors for their efforts and contributions.