Anti-cytokine mAbs in rheumatoid arthritis

TNFa is a potent pro-inflammatory cytokine that has been implicated in the pathogenesis of RA (20). In particular, the TNFa transgenic mice, who express hiunan TNFa constitutively in the joint, develop a spontaneous inflammatoiy arthritis resembling RA (21). Treatment vifith anti-TNFa mAb suppresses inflammation in several animal models of RA (22). In RA patients, TNFo can be foimd both in the blood and the joint particularly at the cartilage-pannus junction (23, 24). 

Anti-TNFa mAbs are highly effective anti-inflammatory treatments although repeated treatments are necessary to maintain disease improvement. However, the duration of clinical improvement may progressively shorten with repeated treatments (29, 30) which may be the result of the anti-antibody response. 

However both mAbs and sTNFR-hIg are expensive to manufacture which is a major disadvantage. Pegylating proteins can reduce their antigenicity and furthermore, the cost of manufacturing such conjugates is less than mAbs and sTNFR-hIg constructs. Pegylated soluble TNF receptor has shown positive results in an early phase l/II study in RA (35). 

Anti-TNFa mAbs are powerful anti-inflammatoiy agents with proven efficacy in RA High dose intravenous treatment produces rapid disease improvement but repeated therapies can lead to significant inunimosuppression with the risk of infection. Frequent subcutaneous low dose treatment may be a safer alternative since the immune response can recover quickly once anti-TNFa mAb therapy is stopped. 

IL-6 is produced by monocytes and qmoviotytes in the synovium. It induces B cells to mature into plasma cells and stimulates hepatocytes to produce acute phase reactants such as C reactive protein (CRP) and serum amyloid A protein. High levels of IL-6 are found in the blood and s5movial fluid of RA patients. Plasma Ifi6 levels correlated with disease activity, eiythrocyte sedimentation rate (ESR), and CRP (36). 

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Anti-cytokine mAbs in rheumatoid arthritis 452 Anti-adhesion molecule mAbs 454 Anti-T cell mAbs in RA 455... 

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