Biological agents in rheumatoid arthritis,fema emergency management college list,safety tips for volcanoes explorers,first aid kit list of contents - And More

Science, Technology and Medicine open access publisher.Publish, read and share novel research. Treatment of Rheumatoid Arthritis with Biological AgentsHiroaki Matsuno1[1] Matsuno Clinic for Rheumatic Diseases, Japan1. Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial.
TEMPO (Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes) study investigators. The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Golimumab, a human antibody to tumour necrosis factor ? given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO-FORWARD Study. Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor alpha inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial. Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis: the RAPID 2 study.
Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist. Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 receptor antagonist, in combination with methotrexate: results of a twenty-four-week, multicenter, randomized, double-blind, placebo-controlled trial. Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: a randomized trial. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis.
Postmarketing surveillance of tocilizumab for rheumatoid arthritis in Japan: interim analysis of 3881 patients. Abatacept SC versus adalimumab on background methotrexate in RA: one year results from the AMPLE study. Tocilizumab (TCZ) monotherapy is superior to adalimumab (ADA) monotherapy in reducing disease activity in patients with rheumatoid arthritis (RA): 24-week data from the phase 4 ADACTA trial. Treatment of rheumatoid synovitis with anti-reshaping human interleukin-6 receptor monoclonal antibody: use of rheumatoid arthritis tissue implants in the SCID mouse model.


TNF induces the production and release of proinflammatory cytokines, such as IL-1, IL-6 and GM-CSF.
Types of Cytokine Inhibitors (Biological Agents) and their effects on Rheumatoid ArthritisCytokine inhibitors used in the treatment of rheumatoid arthritis are inhibitors of IL-1 (anakinra), TNF (infliximab, etanercept, adalimumab, golimumab, and certolizumab pegol), and IL-6 (tocilizumab). Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. TNF also induces the production and release of chemokines, such as CCL5 (also known as RANTES), CCL2 (also known as MCP1) and IL-8, which mediate leukocyte chemoattraction. Experimental monoclonal antibodies are usually produced by immunizing a mouse with an antigen, and therefore, the antibody is 100% mouse antibody. In addition, biological agents other than cytokine inhibitors used in the treatment of rheumatoid arthritis include abatacept, which inhibits the action of T-cell co-stimulatory molecules CD80 and CD86, and rituximab, which targets CD20.These drugs each have a stronger effect than methotrexate(MTX), which is considered to be most effective taken orally, and each has strong action to suppress bone and joint destruction (Figure 3, Figure.
Chemotaxis of leukocytes to areas of inflammation is also mediated by TNF-mediated upregulation of adhesion-molecule expression and increased angiogenesis.
Monocytes differentiate into macrophages and then foam cells, which are key players in atherosclerotic plaque formation.
When such an antibody is used as a therapeutic agent in humans, it causes a strong anaphylactic reaction. TNF induces an increase in the levels of soluble TNF receptors and a decrease in the levels of surface receptors. T lymphocytes also migrate into the vessel wall, where they express chemokine receptors and differentiate into TH1 and TH2 cells. Recommendations for the Use of Biological AgentsOpinion is divided on which biological agent should be used to start with when active rheumatoid arthritis is diagnosed. An increase in the expression of MHC class I and II molecules further contributes to inflammation. Then the antigen binding site is preserved as it is, while the Fc site is artificially replaced with one of human origin such as IgG1 or IgG4.
Among typical rankings for the use of biological agents, there is the 2012 recommendation of the American College of Rheumatology (Figure 5) [20].According to this recommendation, in the United States the first biological agent (1st Bio) recommended for treatment of early rheumatoid arthritis with disease duration of less than 6 months is a TNF inhibitor. TNF contributes to tissue damage through bone resorption and cartilage destruction by inducing production of metalloproteinases and prostaglandin E2.
Thus, anti-TNF biologic agents may be effective in controlling atherosclerosis related to rheumatoid arthritis, ankylosing spondylitis or psoriatic arthritis. In chimeric antibodies, since about 25% mouse protein remains, anaphylactic reactions still occur about 10% of the time when they are administered.


There are also reports of treatment with antibody preparations being impaired when antibodies to the chimeric antibody are produced.A humanized antibody is produced first as a mouse monoclonal antibody, then only the variable parts of the antigen binding site on the heavy chain and light chain of the antibody are left as mouse protein, and the rest is replaced with human protein. Since protein which codes the CDR1, CDR2, and CDR3 regions accounts for about 10% of the total, there is still a small chance of anaphylactic reaction with multiple administrations, though less than that with chimeric antibodies. Selecting Biological Agents by Efficacy and SafetyAmong TNF inhibitors, there are several biological agents to choose from, with no strict standards for which biological agent to use first in either the United States or the United Kingdom. This antibody is produced as follows: An antibody light chain and antibody heavy chain, each with a strong affinity for TNF-?, are selected, and then the two are bound together.
Recently however, data has begun to accumulate suggesting which usage is best.Regarding efficacy, there is data indicating that etanercept is more effective than infliximab for active rheumatoid arthritis with high levels of anti-cyclic citrullinated peptide antibodies and rheumatoid factor [28]. Therefore, while it is a fully human protein, it is not an antibody that is physiologically produced in humans. In addition, among infliximab, adalimumab, and etanercept, it is reported that etanercept shows the highest efficacy in patients with high levels of anti-SS-A antibody [29].With respect to adverse reactions, the occurrence of tuberculosis among patients treated with anti TNF agents has been shown to be low for the fusion protein preparation etanercept and high for the antibody preparations infliximab and adalimumab. Consequently, it is reported that antibodies against the antibody are detected in 40% of cases or more, reducing the function of the antibody preparation. It has been suggested that the reason for this could be that the antibody preparations, unlike the fusion protein preparation etanercept, simultaneously suppress the function of macrophages [30, 31].
Combined use of an immunosuppressant to prevent antibody production is recommended.Another fully humanized antibody on the market is golimumab. Therefore, from the point of view of adverse reactions, etanercept may be the best choice for rheumatoid arthritis patients with a risk of tuberculosis.The same could possibly be considered for tocilizumab, an IL-6 inhibitor which does not directly suppress macrophage function.
First, a humanized transgenic mouse is produced, the mouse is immunized with TNF, and the antibodies produced are purified and commercialized. However, in a study comparing adalimumab and tocilizumab, tocilizumab was shown to be more effective than adalimumab [35] (Table 2).
This method has made it possible to produce an antibody which is closer to human than adalimumab.




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