Rostaing L.Noble J.Malvezzi P.Jouve T.Mahidol University2023-05-192023-05-192023-01-01Expert Opinion on Pharmacotherapy Vol.24 No.2 (2023) , 259-26514656566https://repository.li.mahidol.ac.th/handle/20.500.14594/81524Introduction: Imlifidase, the IgG-degrading enzyme derived from Streptococcus pyogenes, can cleave all four human IgG subclasses with precise specificity. All IgG molecules can be inactivated for ~1-to-2 weeks, until new IgG synthesis is detected. Areas covered: Imlifidase was first studied for the desensitization of highly HLA-sensitized patients to enable kidney transplantation. It is currently being evaluated for kidney transplant recipients who have antibody-mediated rejection (AMR), those with acute kidney injury in the setting of anti-glomerular basement membrane disease, and those with Guillain–Barré syndrome. In 2020, imlifidase received conditional approval from the European Medicines Agency for use to desensitize deceased-donor kidney transplant recipients with a positive crossmatch. Literature search through PubMed revealed that so far, 39 crossmatched-positive patients, i.e. in the presence of donor-specific alloantibodies (DSA) on the transplantation day, have received imlifidase prior to kidney transplantation in four single-arm, open-label, phase II studies. Results at 3-year follow-up are good, i.e. allograft survival is 84%, despite 38% of patients presenting with acute AMR. Mean estimated glomerular filtration rate at 3 years was 55 mL/min/1.73 m2. Expert opinion: The major hurdle now is how to prevent/avoid DSA rebound within days 5–15 post-transplantation. Thus, imlifidase represents a major breakthrough for highly HLA-sensitized kidney transplant candidates, particularly those that have calculated panel-reactive alloantibodies of ≥90%.Pharmacology, Toxicology and PharmaceuticsReviewSCOPUS10.1080/14656566.2022.21509652-s2.0-851426670501744766636404277