Purpose Of Review: This review summarizes the current knowledge of the pathogenic mechanisms of biologics-induced anaphylaxis, and the diagnostic and prophylactic strategies in the management of potentially reactive patients, to improve the safety profile of biologics.
Recent Findings: The recent knowledge on the topic highlights the involvement of both effector and regulatory mechanisms in the immune response to biological agents. In addition, the impact of biological's immunogenicity on hypersensitivity reactions has been confirmed in a wider number of studies, defining some details about the kinetics of antidrug antibodies development, specifically immunoglobulin G (IgG) and immunoglobulin E (IgE).
Summary: Biological agents may induce anaphylaxis, mainly through the induction of antidrug antibodies. Biologics-related infusion reactions are often clinically consistent with type I hypersensitivity, but IgG antidrug antibodies may also be involved. The immune response toward biologicals is orchestrated by both effector and regulatory T cells. In addition, nonantibody-dependent mechanisms may occur. Among clinicians persists today again a low awareness, not only of the possibility to understand the immunological mechanisms behind anaphylaxis to biologicals but also the opportunity to apply potential strategies for the management of reactive patients aimed to guarantee a safe retreatment.
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http://dx.doi.org/10.1097/ACI.0000000000000666 | DOI Listing |
Dig Dis Sci
January 2025
INFINY Institute, Department of Gastroenterology, CHRU Nancy, INSERM NGERE, Université de Lorraine, 54500 , Vandœuvre-lès-Nancy, France.
Background: Therapeutic drug monitoring is important for optimizing anti-tumor necrosis factor-α (TNF-α) therapy in inflammatory bowel disease. However, the exposure-response relationship has never been assessed in pouchitis.
Aims: To explore associations between anti-TNF-α drug concentration and pouchitis disease activity in patients with a background of ulcerative colitis.
Pharmaceuticals (Basel)
January 2025
Department of Paediatrics, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania.
The introduction of anti-tumor necrosis factor-α (anti-TNF-α) agents, particularly infliximab (IFX) and adalimumab (ADA), has significantly expanded the therapeutic arsenal for inflammatory bowel disease (IBD). While these biologics have demonstrated substantial efficacy, they are associated with a spectrum of potential adverse events (AEs). This study aims to evaluate and document these AEs to facilitate optimal patient selection and monitoring strategies of patients undergoing these therapies.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Shimotsuke-shi 329-0498, Tochigi, Japan.
Aflibercept and brolucizumab, two anti-VEGF agents used as intravitreal injections in ophthalmology, differ significantly in molecular weight (aflibercept-115 kDa and brolucizumab-26 kDa). Using aqueous humor samples collected after drug administration, we measured and performed a comparative analysis of pharmacokinetics and half-lives of these drugs in the human eye. Since the quantification of monoclonal antibodies (mAbs) using antigen-antibody reactions, such as ELISA, is influenced by endogenous ligands or anti-drug antibodies, we employed nano-surface and molecular-orientation limited proteolysis (nSMOL), combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS), for accurate measurements.
View Article and Find Full Text PDFMedicina (Kaunas)
January 2025
Laboratory of Specialistic Pediatry, Department of Public Health and Pediatrics, School of Medicine, University of Turin, 10126 Turin, Italy.
: Over the past decade, TNF inhibitors such as Infliximab and Adalimumab have become central to Inflammatory Bowel Diseases treatment, greatly enhancing patient outcomes. However, immunogenicity-where anti-drug antibodies diminish effectiveness-remains an issue, often requiring dose changes or combination therapies. Pharmacogenomics is increasingly applied in IBD to personalise treatment, especially since genetic factors like the HLA-DQA1*05 variant heighten the immunogenicity risk with IFX.
View Article and Find Full Text PDFJ Pediatr Hematol Oncol
January 2025
Department of Paediatric Haematology, NHS Foundation Trust, Birmingham Children's Hospital, Birmingham, UK.
Objective: Emicizumab promotes efficacious hemostasis in persons with hemophilia A persons with hemophilia A with and without inhibitors. Primary analyses of real-world data and clinical trials have shown emicizumab efficacy and safety; however, long-term data are limited.
Methods: This retrospective study was conducted to assess real-world long-term outcomes of pediatric patients on emicizumab in our hemophilia center between the period of February 2018 and September 2023.
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