Abstract

During the past decade biologic therapies such as monoclonal antibodies and fusion proteins have revolutionized the management of rheumatic disease. By targeting key cytokines and immune cells biologics have provided more specific therapeutic interventions with less immunosuppression. Clinical use, however, has revealed that their theoretical simplicity hides a more complex reality. Efficacy, toxicity and even pharmacodynamic effects can deviate from those predicted, as poignantly illustrated by the catastrophic effects witnessed during the first-into-human administration of TGN1412. This review summarizes lessons gleaned from practical experience and discusses how these can inform future discovery and development of new biologic therapies for rheumatology.

Author affiliations

1. Division of Immunology/Rheumatology, Stanford University, 306 Ramona Road, Portola Valley, California 94028, USA.
2. Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, 172 Shelby Interdisciplinary Biomedical Science Building, 1825 University Boulevard, Birmingham, Alabama 35294, USA.
3. Wilson Horne Immunotherapy Centre, Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK

Correspondence to: John D. Isaacs³ Email: J.D.Isaacs@ncl.ac.uk

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