Hypersensitivity reactions to therapeutic monoclonal antibodies: Phenotypes and endotypes - 04/07/18
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.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Monoclonal antibody, hypersensitivity reaction, phenotype, endotype, biomarkers, tryptase, IL-6, skin testing, desensitization, precision medicine
Abbreviations used : HSR, IV
Plan
| L.d.l.V.S. is funded by a postresidency contract “Wenceslao Lopez-Albo” provided by Instituto de Investigacion Marques de Valdecilla (Santander, Spain). |
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| Disclosure of potential conflict of interest: M. Castells reports receiving consultant fees from Sanofi, Merck, Contrafect, Arete Discoveres, Bentham Science; speaking fees from the American College of Allergy, Asthma and Immunology Columbian Allergy Association; and royalties from two publications (“Up To Date”, Anaphylaxis Book). The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 142 - N° 1
P. 159 - juillet 2018 Retour au numéro
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