A total of 326 patients were randomized to receive either TCZ 8 mg/kg every 4 weeks or adalimumab 40 mg subcutaneously every 2 weeks for 24 weeks total. overview of the mode of action, pharmacokinetics, and security of Mirogabalin TCZ. Furthermore, efficacy studies of TCZ as both monotherapy and combination therapy will be evaluated. There have been several important clinical trials evaluating the efficacy and security of TCZ in RA patients; this evaluate summarizes this data from 14 key trials with emphasis on Phase III trials. Review of these trials provides strong evidence that its use, both as monotherapy and in combination with methotrexate or other DMARDs, is an effective treatment in reducing the signs and symptoms of RA. TCZ showed tolerable security but care is required for its use since there are some important safety issues including elevated liver enzymes, elevated low-density lipoprotein, infections, and gastrointestinal perforations. Additionally, given the efficacy of TCZ in the treatment of RA, this review discusses how TCZ may be beneficial in the treatment of other autoimmune diseases, spinal disease, cardiovascular disease, organ transplantation, and malignancies where elevated levels of IL-6 may play a role in the pathogenesis of these diseases. strong class=”kwd-title” Keywords: tocilizumab, IL-6, rheumatoid arthritis, biologics Introduction Rheumatoid arthritis (RA) is usually a chronic systemic inflammatory autoimmune disease causing a symmetrical polyarthritis characterized by prolonged synovitis and destruction of bone and cartilage in multiple joints. RA affects about 1% of adults aged 35 years and 2% of adults aged 60 years and is more common in women.1 The etiology of RA is thought to be multifactorial and is not fully understood; however, proinflammatory cytokines are known to play a role in the disease pathogenesis in RA by propagating inflammation and leading to joint destruction.2 These key cytokines include tumor necrosis factor alpha (TNF-), interleukin (IL)-1, and IL-6.3 First-line drug therapies that are US Food and Drug Administration (FDA)-approved for the treatment of RA include standard disease-modifying antirheumatic drugs (DMARDs) including hydroxychloroquine, methotrexate (MTX), sulfasalazine, and leflunomide. Platinum brokers, cyclosporine, and azathioprine are now rarely used. Nonsteroidal anti-inflammatory medications as well as corticosteroids are generally used in conjunction with DMARDs as adjunctive therapy. For patients with an insufficient response to Mirogabalin these standard brokers, a combination of DMARDs or biological brokers may be indicated. Biologics include the TNF- inhibitors etanercept, adalimumab, infliximab, golimumab, and certolizumab; the IL-1 inhibitor anakinra; the selective modulator of T cell activation, abatacept; and rituximab, a B cell depleting monoclonal antibody directed against the CD20 antigen.4 All of these agents have been successfully used in the treatment of RA, but are not always effective. Of all the biologics listed, anti-TNF- brokers were the first biologics analyzed and Rabbit Polyclonal to Thyroid Hormone Receptor beta approved.5 TNF- inhibitors have been established as an effective treatment option for RA, especially in patients who experience an Mirogabalin inadequate response to the conventional DMARDs listed above, including MTX. There is no direct comparison data between the five currently approved TNF- inhibitors; however, meta-analyses of clinical trial data suggest these compounds have similar efficacy.6 They differ in terms of molecular structures and route of application (subcutaneous versus intravenous). A significant portion of patients have an inadequate response (20%C40%) to anti-TNF- brokers with regards to clinical signs and symptoms.7 The many patients who do not respond to the conventional DMARDs, biologics, or are unable to take these medications secondary to problems with adverse effects produce a demand for new therapies in the treatment of RA. Tocilizumab (TCZ), a new drug targeting the IL-6 pathway, was approved in 2010 2010 for the treatment of moderate to severe RA in patients who have failed other DMARDs, including biologics. It is the first humanized IL-6 receptor-inhibiting monoclonal antibody.8 IL-6 is a 26 kDa glycopeptide. This cytokine plays a role in inflammation, bone metabolism, hematopoiesis, and immune regulation. IL-6 is usually produced by numerous cell types, predominantly macrophages and fibroblasts.9 IL-6 is known to be produced in high quantities in the synovial fluid of patients with RA and these elevations correlate with disease activity and joint destruction.10 The purpose of this paper is to review the role of TCZ in the treatment of RA, focusing on the pharmacology, efficacy, and safety of this drug as exhibited by.