Bestemmelse av tumor nekrose faktor-alfa (TNF-?) ved hjelp av polymerase chain reaction (PCR) teknikk hos pasienter med leddgikt og hos pasienter med inflammatorisk tarmsykdom.
INFLIXIMAB TREATMENT OF RHEUMATOID ARTHRITIS (RA) PATIENTS
Tumor necrosis factor - alpha (TNF-)is an important mediator in the pathogenesis of rheumatoid arthritis (RA). We have investigated long term anti-TNF- treatment with infliximab.
Rheumatoid arthritis (RA) is an autoimmune disease that causes joint inflammation, cartilage damage and bone erosions. The disease affects 0.5- 1% of the population worldwide with a major socio-economic impact to the individual and to the society. Traditionaly, hospitalization has represented the largest direct cost of RA treatment, while medication has been found to constitute less than 25%. The emerging new biologic therapies are efficient and may reduce the need for hospitalization and rehabilitative interventions. Their use is financially challenging and calls for new pharmaco-economic considerations and studies of cost-effectiveness.
Several studies have been done to elucidate the role of TNF-alpha in (RA) and to clarify if it is a suitable target for treating the disease. In transgenic murine models constitutively expressing human TNF-alpha or mice injected with TNF-alpha in the knee joints, the development of chronic arthritis is repressed by anti- TNF-alpha(INFLIXIMAB) treatment. TNF-alpha is an important mediator of other inflammatory/pro-inflammatory cytokines, such as IL-1 and IL-6. IL-6 production is solely activated by TNF-alpha. TNF-alpha also stimulates production of joint destructive matrix metalloproteinases from synoviocytes and the expression of adhesion molecules on endothelial cells in the joint for further recruitment of inflammatory cells. Thus, TNF-alpha has become an important target for treatment of RA.
INFLIXIMAB is a human/murine chimeric monoclonal anti-TNF-alpha antibody of IgG1 kappa isotype, which targets epitopes on the TNF-alpha trimer and renders it biologically inactive. In murine RA models, infliximab treatment led to effective reduction of the arthritis. Infliximab has a half life in circulation of ten days. When distributed in concordance with methotrexate (MTX), an immuno-suppressant, the half life of infliximab is elongated. Clinical studies show that a single infusion of infliximab in patients with RA leads to impressive reduction in pain (60%), stiffness, swelling and tenderness in the joints. Repeated infusions give sustained reduction in symptoms and signs of RA , improve quality of life, and halt progression of joint damage. However, one half to one third of the patients treated with infliximab have been classified as non-responders.
TNF-a gene expression and plasma levels in RA patients Abstract:Tumor necrosis factor- alpha (TNF- ?) is an important mediator i
POSTER:Norsk Biokjemisk Selskaps vintermøte Geilo, 2003.
TNF-a gene expression and plasma levels in RA patients ABSTRACT:Tumor necrosis factor- alpha (TNF- ?) is an important mediator i
POSTER: Summerschool for ph.D studewnts, Middelfart,Den. juni 2003.