title: Clinical pharmacology and therapeutic potential of monoclonal antibody treatment in rheumatoid arthritis.
abstract: Many monoclonal antibodies (mAb) have been tested in rheumatoid arthritis (RA). Murine antibodies were antigenic and caused human antimouse responses in the recipients. As a result, re-treatments were less effective and were associated with an increased risk of anaphylaxis. Advances in biotechnology have allowed us to develop chimaeric and humanised mAb that are less antigenic than their murine equivalents. The specificity of mAb allows targeting of particular inflammatory mediators that are thought to be pathogenic in RA. In clinical trials, anti-cytokine antibodies such as anti-tumour necrosis factor-alpha mAb reduced inflammation rapidly and produced marked symptomatic improvement. The clinical improvement was related to the dosage and plasma concentration of the antibody. When depleting anti-lymphocyte mAb were used in RA, they produced variable clinical responses. One of the explanations for this is the poor penetration of anti-lymphocyte antibodies into the synovial joint. Therefore, depletion of lymphocytes was much greater in the blood than in the synovial joints. Consequently this approach has been abandoned and, recently, nondepleting anti-CD4 mAb have been tested in RA. When sufficient dosages were given, they produced clinical improvement, but more studies are required to assess whether they can lead to long term disease suppression.
authors.affiliation: Rheumatology Unit, Guy's College Hospital, London, England. e.choy@umds.ac.uk
authors.forename: E H
authors.initials: EH
authors.lastname: Choy
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000628:therapy*; D015815:Cell Adhesion Molecules / Q000276:immunology; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000276:immunology; D006801:Humans; D008285:Major Histocompatibility Complex / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016207:Cytokines