Background: Rapid desensitization, a procedure for graded drug administration, allows for the safe readministration of a medication after certain types of hypersensitivity reactions (HSRs) and is indicated in cases in which there are no reasonable therapeutic alternatives. The use of rapid desensitization for HSRs to mAbs has not been validated.
Objective: We sought to describe our experience with rapid desensitization to mAbs, including rituximab, infliximab, and trastuzumab.
Methods: One hundred five rapid desensitizations were performed in 23 patients with a standardized 12-step, 6-hour protocol. Our approach to patient evaluation before desensitization is described. The severity, characteristics, and timing of both initial HSRs and HSRs during desensitization were determined by means of retrospective review of medical records. After a reaction during desensitization, patient-specific protocol modifications were made before each subsequent desensitization.
Results: 104 of 105 desensitizations undertaken were successfully completed. We observed HSRs during 29% of desensitizations, including 27 mild reactions, 1 moderate reaction, and 2 severe reactions. Overall, reactions during desensitization were markedly less severe than initial HSRs, but reactions did recur in a minority of successive desensitizations.
Conclusions: Rapid desensitization is a promising method for the delivery of monoclonal therapeutics after an HSR, but the possibility of a reaction remains with each desensitization.
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http://dx.doi.org/10.1016/j.jaci.2009.09.009 | DOI Listing |
Orphanet J Rare Dis
December 2024
Post Graduate School in Allergology and Internal Medicine "Guido Baccelli", Department of Precision and Regenerative Medicine and Ionian Area-(DiMePRe-J), School of Medicine, Aldo Moro University of Bari, Bari, 70124, Italy.
Background: Mucopolysaccharidosis (MPS) type 1 S and type 2 are rare lysosomal storage disorders characterized by impaired enzyme production, resulting in glycosaminoglycans accumulation within lysosomes. Enzyme Replacement Therapy (ERT) with laronidase and idursulfase are first line treatments, respectively. However, infusion-related hypersensitivity reactions (HR) may lead to ERT discontinuation.
View Article and Find Full Text PDFFront Allergy
December 2024
Allergy Department, Castellon University General Hospital, Castellon de la Plana, Spain.
Background: Hypersensitivity reactions to chemotherapy disrupt treatment schedules and compromise patient outcomes. Rapid Drug Desensitization (RDD) enables patients to tolerate future treatments after an allergy workup. However, Same-Day Desensitization (SDD) is a novel approach that capitalizes on RDD to allow the continuation of chemotherapy on the same day as the index reaction, preventing treatment delays.
View Article and Find Full Text PDFbioRxiv
December 2024
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA.
Calcium (Ca) ions affect nearly all aspects of biology. Excessive Ca entry is cytotoxic and Ca-mobilizing receptors have evolved diverse mechanisms for tight regulation that often include Calmodulin (CaM). TRPA1, an essential Ca-permeable ion channel involved in pain signaling and inflammation, exhibits complex Ca regulation with initial channel potentiation followed by rapid desensitization.
View Article and Find Full Text PDFJ Investig Allergol Clin Immunol
December 2024
Biochemistry-Research Department, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.
Sci Adv
December 2024
Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712, USA.
The nucleus is at the nexus of mechanotransduction and the final barrier for most first line chemotherapeutics. Here, we study the intersection between nuclear-cytoskeletal coupling and chemotherapy nuclear internalization. We find that chronic and acute modulation of intracellular filaments changes nuclear influx of doxorubicin (DOX).
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