Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned?
Rheumatoid arthritis (RA), a systemic disease, is characterized by a chronic inflammatory reaction in the synovium of joints and is associated with degeneration of cartilage and erosion of juxta-articular bone. Many pro-inflammatory cytokines including TNF alpha, chemokines, and growth factors are e...
| Autori principali: | , |
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| Natura: | Journal article |
| Lingua: | English |
| Pubblicazione: |
2001
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| _version_ | 1826295538034671616 |
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| author | Feldmann, M Maini, R |
| author_facet | Feldmann, M Maini, R |
| author_sort | Feldmann, M |
| collection | OXFORD |
| description | Rheumatoid arthritis (RA), a systemic disease, is characterized by a chronic inflammatory reaction in the synovium of joints and is associated with degeneration of cartilage and erosion of juxta-articular bone. Many pro-inflammatory cytokines including TNF alpha, chemokines, and growth factors are expressed in diseased joints. The rationale that TNF alpha played a central role in regulating these molecules, and their pathophysiological potential, was initially provided by the demonstration that anti-TNF alpha antibodies added to in vitro cultures of a representative population of cells derived from diseased joints inhibited the spontaneous production of IL-1 and other pro-inflammatory cytokines. Systemic administration of anti-TNF alpha antibody or sTNFR fusion protein to mouse models of RA was shown to be anti-inflammatory and joint protective. Clinical investigations in which the activity of TNF alpha in RA patients was blocked with intravenously administered infliximab, a chimeric anti-TNF alpha monoclonal antibody (mAB), has provided evidence that TNF regulates IL-6, IL-8, MCP-1, and VEGF production, recruitment of immune and inflammatory cells into joints, angiogenesis, and reduction of blood levels of matrix metalloproteinases-1 and -3. Randomized, placebo-controlled, multi-center clinical trials of human TNF alpha inhibitors have demonstrated their consistent and remarkable efficacy in controlling signs and symptoms, with a favorable safety profile, in approximately two thirds of patients for up to 2 years, and their ability to retard joint damage. Infliximab (a mAB), and etanercept (a sTNF-R-Fc fusion protein) have been approved by regulatory authorities in the United States and Europe for treating RA, and they represent a significant new addition to available therapeutic options. |
| first_indexed | 2024-03-07T04:02:35Z |
| format | Journal article |
| id | oxford-uuid:c5162f5a-da69-462f-a7a9-3f089a5d3d92 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:02:35Z |
| publishDate | 2001 |
| record_format | dspace |
| spelling | oxford-uuid:c5162f5a-da69-462f-a7a9-3f089a5d3d922022-03-27T06:28:23ZAnti-TNF alpha therapy of rheumatoid arthritis: what have we learned?Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c5162f5a-da69-462f-a7a9-3f089a5d3d92EnglishSymplectic Elements at Oxford2001Feldmann, MMaini, RRheumatoid arthritis (RA), a systemic disease, is characterized by a chronic inflammatory reaction in the synovium of joints and is associated with degeneration of cartilage and erosion of juxta-articular bone. Many pro-inflammatory cytokines including TNF alpha, chemokines, and growth factors are expressed in diseased joints. The rationale that TNF alpha played a central role in regulating these molecules, and their pathophysiological potential, was initially provided by the demonstration that anti-TNF alpha antibodies added to in vitro cultures of a representative population of cells derived from diseased joints inhibited the spontaneous production of IL-1 and other pro-inflammatory cytokines. Systemic administration of anti-TNF alpha antibody or sTNFR fusion protein to mouse models of RA was shown to be anti-inflammatory and joint protective. Clinical investigations in which the activity of TNF alpha in RA patients was blocked with intravenously administered infliximab, a chimeric anti-TNF alpha monoclonal antibody (mAB), has provided evidence that TNF regulates IL-6, IL-8, MCP-1, and VEGF production, recruitment of immune and inflammatory cells into joints, angiogenesis, and reduction of blood levels of matrix metalloproteinases-1 and -3. Randomized, placebo-controlled, multi-center clinical trials of human TNF alpha inhibitors have demonstrated their consistent and remarkable efficacy in controlling signs and symptoms, with a favorable safety profile, in approximately two thirds of patients for up to 2 years, and their ability to retard joint damage. Infliximab (a mAB), and etanercept (a sTNF-R-Fc fusion protein) have been approved by regulatory authorities in the United States and Europe for treating RA, and they represent a significant new addition to available therapeutic options. |
| spellingShingle | Feldmann, M Maini, R Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned? |
| title | Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned? |
| title_full | Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned? |
| title_fullStr | Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned? |
| title_full_unstemmed | Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned? |
| title_short | Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned? |
| title_sort | anti tnf alpha therapy of rheumatoid arthritis what have we learned |
| work_keys_str_mv | AT feldmannm antitnfalphatherapyofrheumatoidarthritiswhathavewelearned AT mainir antitnfalphatherapyofrheumatoidarthritiswhathavewelearned |