Drug hypersensitivity reactions: review of the state of the science for prediction and diagnosis

Author:

Pallardy Marc1,Bechara Rami2,Whritenour Jessica3,Mitchell-Ryan Shermaine4,Herzyk Danuta5,Lebrec Herve6,Merk Hans7,Gourley Ian8,Komocsar Wendy J9,Piccotti Joseph R10,Balazs Mercedesz11,Sharma Amy12,Walker Dana B13,Weinstock Daniel14

Affiliation:

1. Université Paris-Saclay, INSERM, Inflammation Microbiome Immunosurveillance , Orsay, 91400, France

2. Université Paris-Saclay, INSERM, CEA, Center for Research in Immunology of Viral, Autoimmune, Hematological and Bacterial Diseases (IMVA-HB) , Le Kremlin Bicêtre, 94270, France

3. Pfizer Worldwide Research, Development and Medical , Groton, Connecticut 06340, USA

4. The Health and Environmental Science Institute, Immunosafety Technical Committee , Washington, District of Columbia 20005, USA

5. Merck & Co., Inc , West Point, Pennsylvania 19486, USA

6. Amgen Inc., Translational Safety and Bioanalytical Sciences , South San Francisco, California 94080, USA

7. Department of Dermatology and Allergology, RWTH Aachen University , Aachen, 52062, Germany

8. Janssen Research & Development, LLC, Immunology Clinical Development , Spring House, Pennsylvania 19002, USA

9. Immunology Business Unit, Eli Lilly and Company , Indianapolis, Indiana 46225, USA

10. Drug Discovery, Schrodinger, Inc , San Diego, California 92121, USA

11. Genentech, Biochemical and Cellular Pharmacology , South San Francisco, California 94080, USA

12. Pfizer, Drug Safety Research & Development , New York 10017, USA

13. Novartis Institute for Biomedical Research, Preclinical Safety-Translational Immunology and Clinical Pathology , Cambridge, Massachusetts 02139, USA

14. Janssen Research & Development, LLC, Preclinical Sciences Translational Safety , Spring House, Pennsylvania 19002, USA

Abstract

Abstract Drug hypersensitivity reactions (DHRs) are a type of adverse drug reaction that can occur with different classes of drugs and affect multiple organ systems and patient populations. DHRs can be classified as allergic or non-allergic based on the cellular mechanisms involved. Whereas nonallergic reactions rely mainly on the innate immune system, allergic reactions involve the generation of an adaptive immune response. Consequently, drug allergies are DHRs for which an immunological mechanism, with antibody and/or T cell, is demonstrated. Despite decades of research, methods to predict the potential for a new chemical entity to cause DHRs or to correctly attribute DHRs to a specific mechanism and a specific molecule are not well-established. This review will focus on allergic reactions induced by systemically administered low-molecular weight drugs with an emphasis on drug- and patient-specific factors that could influence the development of DHRs. Strategies for predicting and diagnosing DHRs, including potential tools based on the current state of the science, will also be discussed.

Publisher

Oxford University Press (OUP)

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