TY - JOUR
T1 - Hypersensitivity and immunologic reactions to biologics
T2 - opportunities for the allergist
AU - Khan, David A.
N1 - Publisher Copyright:
© 2016 American College of Allergy, Asthma & Immunology
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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, including omalizumab, rituximab, TGN1412, biologic agent, anaphylaxis, hypogammaglobulinemia, desensitization, and cytokine 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.
AB - 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, including omalizumab, rituximab, TGN1412, biologic agent, anaphylaxis, hypogammaglobulinemia, desensitization, and cytokine 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.
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U2 - 10.1016/j.anai.2016.05.013
DO - 10.1016/j.anai.2016.05.013
M3 - Review article
C2 - 27499538
AN - SCOPUS:84991738442
SN - 1081-1206
VL - 117
SP - 115
EP - 120
JO - Annals of Allergy, Asthma and Immunology
JF - Annals of Allergy, Asthma and Immunology
IS - 2
ER -