Imlifidase therapy: exploring its clinical uses. (22nd January 2023)

• Record Type: Journal Article
• Authors: Rostaing, Lionel; Noble, Johan; Malvezzi, Paolo; Jouve, Thomas
• Is Part Of: Expert opinion on pharmacotherapy. Volume 24:Number 2(2023)
• Page Start: 259
• Page End: 265
• Publication Date: 2023-01-22
• Subjects: Antibody-mediated rejection -- anti-GBM disease -- desensitization -- donor-specific alloantibody -- IgG -- imlifidase -- IdeS -- kidney transplantation -- positive crossmatch -- Streptococcus pyogenes; Chemotherapy -- Periodicals; 615.5805
• DOI: 10.1080/14656566.2022.2150965
• Languages: English
• ISSNs: 1465-6566

Abstract

ABSTRACT: Introduction: 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 m 2 . 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%.