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Secondary immunodeficiency induced by biologic therapies

Mark Ballow, MD
Thomas A Fleisher, MD
Section Editor
E Richard Stiehm, MD
Deputy Editor
Anna M Feldweg, MD


Biologic therapies typically do not cause the global immunosuppression that is characteristic of traditional immunosuppressive drugs, such as glucocorticoids, cyclosporine, methotrexate, and azathioprine. However, biologics can have unintended effects on immune function that can compromise host defenses and lead to serious infections. Other manifestations of immunosuppression, such as the development of autoimmune diseases or malignancies, may also occur with some of these therapies. Biologics that cause immunosuppression, either as the primary therapeutic goal or as an unintended side effect, and the immunologic mechanisms through which this occurs, will be reviewed here. This topic is not comprehensive. Only representative examples of biologics resulting in a consistent and marked impairment in immune function are discussed. In addition, many new biologics targeting the immune system are under development with varying degrees of infectious complications [1-3].

The management of drug-induced immunodeficiency may include regimens of prophylactic antibiotics or antivirals or immune globulin for the treatment of hypogammaglobulinemia. These issues are discussed elsewhere in the program in relation to specific diseases, and links are provided throughout this topic.


Biologic therapies that can increase the risk of infectious diseases include antithymocyte globulin (ATG), monoclonal antibodies to T and B cells, anticytokine therapies, and agents that disrupt T cell costimulation signals. These agents selectively target cells and pathways of the immune system to achieve specific therapeutic effects and are used primarily in the treatment of rheumatic, inflammatory, and malignant diseases. An overview of the use of these agents in rheumatic disorders is found elsewhere. (See "Overview of biologic agents and kinase inhibitors in the rheumatic diseases".)

Factors that increase the risk of infectious complications — With any biologic agent, the likelihood of clinically significant infection primarily depends upon the actions of the drug in question, its dose, and the duration of treatment. In addition, there are other patient-specific factors that contribute to the risk. The most important are:

The nature of the underlying disease process – For example, a patient who is given an immunosuppressive drug shortly after undergoing hematopoietic cell transplantation (HCT) for malignancy may be at greater risk than a patient receiving the same drug for chronic, stable rheumatologic disease.

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Literature review current through: Nov 2017. | This topic last updated: Jun 30, 2016.
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