Ghislaine Annie C Isabwe1, Marlene Garcia Neuer2, Leticia de Las Vecillas Sanchez3, Donna-Marie Lynch2, Kathleen Marquis2, Mariana Castells4. 1. Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; Division of Allergy and Immunology, Department of Pediatrics, Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, Quebec, Canada. 2. Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass. 3. Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; Department of Allergy, Marqués de Valdecilla University Hospital-Instituto de Investigacion Marques de Valdecilla, Santander, Spain. 4. Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass. Electronic address: mcastells@bwh.harvard.edu.
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.
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.
Authors: Timothy E Dribin; David Schnadower; Julie Wang; Carlos A Camargo; Kenneth A Michelson; Marcus Shaker; Susan A Rudders; David Vyles; David B K Golden; Jonathan M Spergel; Ronna L Campbell; Mark I Neuman; Peter S Capucilli; Michael Pistiner; Mariana Castells; Juhee Lee; David C Brousseau; Lynda C Schneider; Amal H Assa'ad; Kimberly A Risma; Rakesh D Mistry; Dianne E Campbell; Margitta Worm; Paul J Turner; John K Witry; Yin Zhang; Brad Sobolewski; Hugh A Sampson Journal: J Allergy Clin Immunol Date: 2021-08-12 Impact factor: 10.793
Authors: Simbarashe Takuva; Shelly T Karuna; Michal Juraska; Erika Rudnicki; Srilatha Edupuganti; Maija Anderson; Robert De La Grecca; Martin R Gaudinski; Alice Sehurutshi; Catherine Orrell; Logashvari Naidoo; Javier Valencia; Larissa M Villela; Stephen R Walsh; Philip Andrew; Carissa Karg; April Randhawa; John Hural; Margarita M Gomez Lorenzo; David N Burns; Julie Ledgerwood; John R Mascola; Myron Cohen; Lawrence Corey; Kathy Mngadi; Nyaradzo M Mgodi Journal: J Acquir Immune Defic Syndr Date: 2022-04-01 Impact factor: 3.771