Clinical Efficacy of TNF-áInhibitors: An Update
Huseyin TE Ozer; Zeynep Ozbalkan
Abstract and Introduction
Abstract
Over the last decade, TNF-á antagonists became the most powerful tools for controlling patient suffering from a number of rheumatic diseases. Infliximab, etanercept and adalimumab can induce remission and prevent both clinical and radiological disease progression in rheumatoid arthritis with significant improvement in patients' symptoms, function and quality of life. They improve joint symptoms and significantly retard radiographic progression in psoriatic arthritis. TNF-á antagonists have been demonstrated to reduce disease activity, retard radiologic progression and increase quality of life in ankylosing spondylitis patients. Long-term follow-up studies demonstrated sustained efficacy and acceptable safety profiles that were comparable in rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis.
Etanercept is the only US FDA-approved TNF antagonist for juvenile rheumatoid arthritis. TNF-áantagonists may improve some clinical manifastations of Behcet's disases, including uveitis. Tuberculosis and some other granulomatous infections are likely to occur more frequently among patients treated with monoclonal antibodies than among those treated with soluble TNF receptors. During the first 6 years of therapy, no overall elevation of cancer risk was observed with any of the three TNF antagonists. TNF antagonists were not associated with any major further increase in the already increased lymphoma risk in rheumatoid arthritis. Frequent monitoring of serum transaminase levels and viral load was suggested for TNF antagonist use in hepatitis B and C infection. They might reduce some important costs to the patients; however, studies with additional detailed cost calculations are required.
Introduction
Rheumatoid arthritis (RA) is a progressive, destructive, inflammatory disease resulting in disability and death. It is one of the most frequent chronic inflammatory joint disease as it affects approximately 0.51% of the world's population. It has a significant negative impact on quality of life, with job functioning as well as resultant healthcare costs to the community.
Treatment concepts of the disease have undergone major changes over the last 100 years. Various agents known as disease-modifying antirheumatic drugs (DMARDs), of which methotrexate (MTX) is currently widely used alone or in combination with other DMARDs, are used as treatment. Other DMARDs include sulfasalazine, hydroxychlorokin and leflunomide.
Induction of remission state can be achieved by combining with the available potent biological agents as early as possible. RA etiology remains unknown, but a 20-year study on its pathogenesis has led to identification of new therapeutic targets. Many of the new medications modify the immune response by blocking the effects of proinflammatory cytokines, or by affecting immune cells, such as B lymphocytes, or on interaction with T cells and antigen-presenting cells. It has been found that TNF-á plays a pivotal role in the pathogenesis of inflammed synovium in RA.[13] However, TNF is not the only cytokine involved in the pathogenesis of RA. IL-1 and IL-6 receptor antagonists also play an important role by inhibiting disease activity.
Depleting circulating CD20+ B lymphocytes using monoclonal anti-CD20 antibodies or by blocking the costimulatory signal (CD28-CD80/86) for T-cell/antigen-presenting cell interactions are other therapeutic options in patients resistant to TNF-á inhibitors. The TNF inhibitors that have been approved for clinical use to treat RA are infliximab, adalimumab and etanercept. Infliximab is a chimeric mousehuman monoclonal antibody, whereas adalumimab is a fully humanized monoclonal antibody; both agents are specific for TNF. Etanercept is a fusion protein comprising the ligand-binding portion of the human p75 TNF receptor (TNFRIII) and the Fc fragment of human IgG1. The TNF inhibitors cause their primary effect by blocking the interaction of TNF with cell surface receptors. Biologic anti-TNF, often used in combination with MTX, is now the first choice of treatment when other DMARDs fail in clinical practice.
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Abstract
Over the last decade, TNF-á antagonists became the most powerful tools for controlling patient suffering from a number of rheumatic diseases. Infliximab, etanercept and adalimumab can induce remission and prevent both clinical and radiological disease progression in rheumatoid arthritis with significant improvement in patients' symptoms, function and quality of life. They improve joint symptoms and significantly retard radiographic progression in psoriatic arthritis. TNF-á antagonists have been demonstrated to reduce disease activity, retard radiologic progression and increase quality of life in ankylosing spondylitis patients. Long-term follow-up studies demonstrated sustained efficacy and acceptable safety profiles that were comparable in rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis.
Etanercept is the only US FDA-approved TNF antagonist for juvenile rheumatoid arthritis. TNF-áantagonists may improve some clinical manifastations of Behcet's disases, including uveitis. Tuberculosis and some other granulomatous infections are likely to occur more frequently among patients treated with monoclonal antibodies than among those treated with soluble TNF receptors. During the first 6 years of therapy, no overall elevation of cancer risk was observed with any of the three TNF antagonists. TNF antagonists were not associated with any major further increase in the already increased lymphoma risk in rheumatoid arthritis. Frequent monitoring of serum transaminase levels and viral load was suggested for TNF antagonist use in hepatitis B and C infection. They might reduce some important costs to the patients; however, studies with additional detailed cost calculations are required.
Introduction
Rheumatoid arthritis (RA) is a progressive, destructive, inflammatory disease resulting in disability and death. It is one of the most frequent chronic inflammatory joint disease as it affects approximately 0.51% of the world's population. It has a significant negative impact on quality of life, with job functioning as well as resultant healthcare costs to the community.
Treatment concepts of the disease have undergone major changes over the last 100 years. Various agents known as disease-modifying antirheumatic drugs (DMARDs), of which methotrexate (MTX) is currently widely used alone or in combination with other DMARDs, are used as treatment. Other DMARDs include sulfasalazine, hydroxychlorokin and leflunomide.
Induction of remission state can be achieved by combining with the available potent biological agents as early as possible. RA etiology remains unknown, but a 20-year study on its pathogenesis has led to identification of new therapeutic targets. Many of the new medications modify the immune response by blocking the effects of proinflammatory cytokines, or by affecting immune cells, such as B lymphocytes, or on interaction with T cells and antigen-presenting cells. It has been found that TNF-á plays a pivotal role in the pathogenesis of inflammed synovium in RA.[13] However, TNF is not the only cytokine involved in the pathogenesis of RA. IL-1 and IL-6 receptor antagonists also play an important role by inhibiting disease activity.
Depleting circulating CD20+ B lymphocytes using monoclonal anti-CD20 antibodies or by blocking the costimulatory signal (CD28-CD80/86) for T-cell/antigen-presenting cell interactions are other therapeutic options in patients resistant to TNF-á inhibitors. The TNF inhibitors that have been approved for clinical use to treat RA are infliximab, adalimumab and etanercept. Infliximab is a chimeric mousehuman monoclonal antibody, whereas adalumimab is a fully humanized monoclonal antibody; both agents are specific for TNF. Etanercept is a fusion protein comprising the ligand-binding portion of the human p75 TNF receptor (TNFRIII) and the Fc fragment of human IgG1. The TNF inhibitors cause their primary effect by blocking the interaction of TNF with cell surface receptors. Biologic anti-TNF, often used in combination with MTX, is now the first choice of treatment when other DMARDs fail in clinical practice.
DOWNLOAD COMPLETE PDF HERE
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