The Journal of Allergy and Clinical Immunology: In Practice
Review and Feature ArticleA Review of Adverse Reactions to Biologics Used in Allergy-Immunology Practice
Section snippets
Overview of Biologics
Biologic therapies encompass a diverse range of products including vaccines, blood components, allergenic extract, somatic cells, gene therapy, cytokines, monoclonal antibodies, and fusion proteins.1 These therapies have revolutionized the treatment of conditions throughout the field of allergy and immunology. Widespread use has resulted in increased understanding of adverse reactions associated with these therapies including underlying mechanisms, classification, diagnostics, and management.
Classification of Adverse Reactions
Although various definitions of biologic therapies exist, biologics are derived from microorganisms or mammalian cells and are typically large complex molecules such as proteins or polypeptides.1 This contrasts with most drugs that are chemically synthesized, well-characterized small molecules, often with molecular weights less than 1 kDa. Furthermore, monoclonal antibodies and fusion receptor proteins have inherent immune-mediated effects that underlie their intended activity, whereas for most
Diagnostic Strategies
Careful clinical history is essential for determining subsequent diagnostic strategies. As discussed above, certain clinical features may suggest an underlying endotype to which targeted testing may be helpful; however, there is often a significant overlap of clinical symptoms across different endotypes, and diagnostic and management protocols have not yet been standardized.
Management
The proposed classification of infusion-related reactions (cytokine release reactions, type 1 reactions, mixed reactions, and delayed reactions) can help to direct the management approach. An example of 1 management algorithm is listed in Figure 1.
Injection site reactions can be treated with optimizing administration through rotating injection sites, avoiding sensitive locations, and if allowed, placing the biologic at room temperature before injection; furthermore, cold compresses, analgesics,
Omalizumab
Omalizumab was the first biologic agent approved for the treatment of allergic disease. First approved in 2003 for the treatment of moderate-to-severe asthma, further approvals have included indications for chronic spontaneous urticaria in 2014 and for adults with nasal polyps in 2020. Omalizumab is a chimeric human-mouse recombinant antibody that binds to the domain at which IgE binds to FϲεRI on mast cells and basophils.23,24 Its primary mechanism of action is binding of free IgE in the
Conclusion
As the use of biologic agents continues to rise across medicine especially within the field of allergy and immunology, adverse reactions will likely continue to be encountered with increasing frequency. Additional research is needed to better understand the utility of available testing, improved testing methods, and determine genetic factors that may increase the risk of AEs. Despite this, management tools such as rapid drug desensitizations can be used to safely administer biologics in many
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Cited by (1)
Research Advances in Mast Cell Biology and Their Translation Into Novel Therapies for Anaphylaxis
2023, Journal of Allergy and Clinical Immunology: In Practice
No funding was received for this work.
Conflicts of interest: S. R. Joshi has participated on advisory boards for Biocryst, Sanofi, Noho Allergy, Takeda, and Leo Pharma, and declares that he is a consultant and owns stock in Nectar Allergy. J. Oppenheimer declares that he is on the data and safety monitoring board for AstraZeneca, Amgen, GlaxoSmithKline, Sanofi/Regeneron, and Abbvie. He is a consultant for GlaxoSmithKline, Aquestive, Aimmune, and Amgen; and is an executive editor for Annals of Allergy, Asthma, and Immunology, UpToDate reviewer, and section editor for Medscape. T. G. Chow declares that he received the Allergists’ Foundation Community Grant (ACAAI) and was ACAAI Fellow-in-Training representative to the Board of Regents 2019-2021.