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5.
J Allergy Clin Immunol ; 142(1): 159-170.e2, 2018 07.
Article in English | MEDLINE | ID: mdl-29518427

ABSTRACT

BACKGROUND: The increasing use of mAbs has led to a rise in hypersensitivity reactions (HSRs), which prevent their use as first-line therapy. HSRs' symptoms, diagnostic tools, and directed management approaches have not been standardized. OBJECTIVE: We propose a novel evidence-based classification of HSRs to mAbs, based on the clinical phenotypes, underlying endotypes and biomarkers, as well as their management with desensitization. METHODS: Phenotypes, endotypes, and biomarkers of HSRs to 16 mAbs for 104 patients were described and compared with the outcomes of 526 subcutaneous and intravenous desensitizations. RESULTS: Initial reactions presented with 4 patterns: type I-like reactions (63%), cytokine-release reactions (13%), mixed reactions (21%), and delayed type IV reactions (3%). In contrast, of the 23% breakthrough HSRs during desensitization, 52% were cytokine-release reactions, 32% were type 1, 12% were mixed, and 4% were type I with delayed type IV. Skin testing to 10 mAbs in 58 patients was positive in 41% of patients. Serum tryptase was elevated in 1 patient and IL-6 was elevated in 8 patients during desensitization and was associated with a cytokine-release phenotype. CONCLUSIONS: HSRs to mAbs can be defined as type I, cytokine-release, mixed (type I/cytokine-release), and type IV reactions, which are identified by biomarkers such as skin test, tryptase, and IL-6. These phenotypes can be used to improve personalized and precision medicine when diagnosing HSRs to mAbs and providing management recommendations with desensitization. Desensitization provides a safe and effective retreatment option to remain on culprit mAbs as first-line therapy.


Subject(s)
Antibodies, Monoclonal/adverse effects , Desensitization, Immunologic/methods , Drug Hypersensitivity/classification , Drug Hypersensitivity/prevention & control , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/immunology , Female , Humans , Male , Middle Aged , Phenotype , Retrospective Studies , Young Adult
6.
Allergy Asthma Proc ; 38(6): 409-418, 2017 Nov 01.
Article in English | MEDLINE | ID: mdl-29046192

ABSTRACT

Hypersensitivity reactions (HSR) to targeted biologic agents present as immediate reactions during infusion or as delayed reactions (after one or more exposures). The new classification includes phenotypes, endotypes, and biomarkers. Phenotypes include immediate type I (immunoglobulin E [IgE] or non-IgE mediated), cytokine release, mixed (type I/cytokine), and immune complexes type III (IgG mediated) reactions as well as delayed type IV reactions. Endotypes include IgE or non-IgE mediated mast cells/basophils activation with elevated serum tryptase and T cells values as well as macrophages, which lead to cytokine production, e.g., interleukin 6. A skin test is a valuable tool in evaluating HSRs to biologics; however, its predictive value depends on the type of reaction and the monoclonal antibody. Desensitization is a new approach to safely reintroduce biologics when they are first-line therapies, and it is available for immediate and delayed reactions. Research is needed to further understand the mechanisms of reactions to monoclonal antibodies and their management.


Subject(s)
Biological Factors/adverse effects , Desensitization, Immunologic/methods , Drug Hypersensitivity/therapy , Biological Factors/immunology , Biological Factors/therapeutic use , Biomarkers , Humans , Phenotype
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