Combination biologic therapy

J.D. Isaacs¹, A.W. Morgan¹, V. Strand²

¹Department of Rheumatology, University of Leeds, UK; ²Division of Immunology, Stanford University, Palo Alto, California, USA.

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-TNFa) 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 TNFa blockade are underway; combination use of TNFa and interleukin-1b 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.

Key words
Immunotherapy, biologic therapy, combination therapy, anti-CD4, anti-TNFa.

Please address correspondence and reprint requests to: John D. Isaacs, PhD, FRCP, Molecular Medicine Unit, Clinical Sciences Building, St James’s University Hospital, Leeds LS9 7TF, UK.
E-mail: rrrjdi@leeds.ac.uk

Clin Exp Rheumatol 1999; 17 (Suppl. 18): S121 - S124.
© Copyright Clinical and Experimental Rheumatology 1999.