title: Combination biologic therapy.
abstract: Biologic therapies refer to genetically engineered treatments such as monoclonal antibodies and receptor-immunoglobulin fusion proteins. Following many disappointments, the introduction of anti-tumor necrosis factor (anti-TNF alpha) therapies into the clinic has clearly demonstrated the exciting potential of biologic agents. Many of these have been designed to modulate a specific aspect of the underlying autoimmune process, thus avoiding generalized immunosuppression. They include products which interfere with the trimolecular complex of major histocompatibility complex II-Antigen-T cell receptor interaction; others designed to block the secondary signals for T cell activation and T cell interaction with antigen-presenting cells; and cytokine agonists as well as antagonists. Whilst reducing the degree of global immunosuppression associated with therapy, this targeted specificity may reduce the likelihood that a single therapeutic agent will provide long-term disease control. On the other hand, animal models have demonstrated synergy of combination biologic therapy, particularly for the re-induction of self-tolerance. As our knowledge of immune physiology and, particularly, immune regulation improves, it can be expected that many combination biologic therapies will be tested in the clinic. Pilot studies of combined anti-CD4 and TNF alpha blockade are underway; combination use of TNF alpha and interleukin-1 beta inhibitors are expected. This article reviews the potential for combination biologic therapy, including likely adverse effects, for the treatment of rheumatoid arthritis and other autoimmune diseases.
authors.affiliation: Department of Rheumatology, University of Leeds, UK. rrrjdi@leeds.ac.uk
authors.forename: J D
authors.initials: JD
authors.lastname: Isaacs
authors.forename: A W
authors.initials: AW
authors.lastname: Morgan
authors.forename: V
authors.initials: V
authors.lastname: Strand
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000276:immunology* / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D004359:Drug Therapy, Combination; D006801:Humans; D007167:Immunotherapy
chemical_list: D018501:Antirheumatic Agents