Hypersensitivity and immunologic reactions to biologics: opportunities for the allergist

David A. Khan, MDPress enter key for correspondence informationPress enter key to Email the author

Department of Internal Medicine, Division of Allergy and Immunology, University of Texas Southwestern Medical Center, Dallas, Texas

DOI: http://dx.doi.org/10.1016/j.anai.2016.05.013

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• Abstract

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Article Outline

1. Introduction
2. High Cytokine (Cytokine Release and Storm) Reactions
3. Common Acute Infusion Reactions
4. Hypersensitivity Reactions
5. Omalizumab
   1. Anaphylaxis to Omalizumab
   2. Proposed Mechanisms of Omalizumab Anaphylaxis
   3. Omalizumab Skin Testing
   4. Omalizumab Desensitization
   5. Omalizumab Serum Sickness-Like Reactions
6. Rituximab
   1. Immunodeficiency
   2. Serum Sickness-Like Reactions
   3. Anaphylaxis and Skin Testing
   4. Rapid Desensitization
7. Conclusions
8. References

Abstract

Jump to SectionIntroductionHigh Cytokine (Cytokine Release and Storm) ReactionsCommon Acute Infusion ReactionsHypersensitivity ReactionsOmalizumab  Anaphylaxis to Omalizumab  Proposed Mechanisms of Omalizumab Anaphylaxis  Omalizumab Skin Testing  Omalizumab Desensitization  Omalizumab Serum Sickness-Like ReactionsRituximab  Immunodeficiency  Serum Sickness-Like Reactions  Anaphylaxis and Skin Testing  Rapid DesensitizationConclusionsReferences

Objective

There has been a great expanse in the use of biological agents during the past decade. However, there are significant differences between biologics and typical pharmaceutical drugs. This review focuses on 3 separate types of adverse reactions to biologics, namely high cytokine reactions, hypersensitivity reactions, and secondary immunodeficiency.

Data Sources

A PubMed literature search restricted to the previous 10 years using combinations of search terms, includingomalizumab, rituximab, TGN1412, biologic agent, anaphylaxis, hypogammaglobulinemia, desensitization, andcytokine storm, was performed. The results were manually filtered to identify relevant articles with additional references identified from bibliographies.

Study Selection

Reports were selected for TGN1412 cytokine storm, omalizumab anaphylaxis and desensitization, rituximab-induced hypogammaglobulinemia, rituximab anaphylaxis and serum sickness, and monoclonal antibody desensitization.

Results

A phase 1 clinical trial using a humanized anti-CD28 monoclonal antibody (TGN1412) caused severe cytokine storm reactions in all 6 subjects, resulting in multiorgan failure. Omalizumab has been reported to cause anaphylaxis in fewer than 0.1% of patients, many with delayed reactions. The mechanism for this anaphylactic reaction is unclear. Rituximab has been associated with hypogammaglobulinemia, serum sickness-like reactions, and anaphylaxis. Rapid drug desensitizations to monoclonal antibodies, including rituximab, suspected of causing immunoglobulin E-mediated reactions have been found to be generally safe and effective.

Conclusion

Hypersensitivity reactions and immune dysregulation from biologic agents are not rare. The allergist and immunologist should be involved in managing these patients for optimal care.