Imlifidase Desensitization in Crossmatch-positive, Highly Sensitized Kidney Transplant Recipients: Results of an International Phase 2 Trial (Highdes)

Autor: Lena Winstedt, Christian Kjellman, Elisabeth Sonesson, Tomas Lorant, Mats Bengtsson, Anna Runström, Bonnie E. Lonze, Christophe Legendre, Robert A. Montgomery, Stanley C. Jordan, Åsa Schiött, Lena Laxmyr, Kathryn J. Wood, Niraj M. Desai, Kristoffer Sjöholm, Ashley Vo
Rok vydání: 2020
Předmět:
Adult
Graft Rejection
Male
medicine.medical_specialty
medicine.medical_treatment
Renal function
030230 surgery
Gastroenterology
Vulnerable Populations
03 medical and health sciences
Young Adult
0302 clinical medicine
Pharmacokinetics
Bacterial Proteins
Isoantibodies
Internal medicine
Biopsy
medicine
Humans
Adverse effect
Kidney transplantation
Desensitization (medicine)
Transplantation
medicine.diagnostic_test
biology
business.industry
Kirurgi
Histocompatibility Testing
Graft Survival
Immunology in the medical area
Original Clinical Science—General
Middle Aged
medicine.disease
Kidney Transplantation
Tissue Donors
Desensitization
Immunologic
Pharmacodynamics
Immunologi inom det medicinska området
biology.protein
ComputingMethodologies_DOCUMENTANDTEXTPROCESSING
030211 gastroenterology & hepatology
Surgery
Female
Antibody
business
Zdroj: Transplantation
ISSN: 1534-6080
Popis: Supplemental Digital Content is available in the text.
Background. Highly HLA sensitized patients have limited access to life-saving kidney transplantation because of a paucity of immunologically suitable donors. Imlifidase is a cysteine protease that cleaves IgG leading to a rapid decrease in antibody level and inhibition of IgG-mediated injury. This study investigates the efficacy and safety of imlifidase in converting a positive crossmatch test to negative, allowing highly sensitized patients to be transplanted with a living or deceased donor kidney. Methods. This open-label, single-arm, phase 2 trial conducted at 5 transplant centers, evaluated the ability of imlifidase to create a negative crossmatch test within 24 h. Secondary endpoints included postimlifidase donor-specific antibody levels compared with predose levels, renal function, and pharmacokinetic/pharmacodynamic profiles. Safety endpoints included adverse events and immunogenicity profile. Results. Of the transplanted patients, 89.5% demonstrated conversion of baseline positive crossmatch to negative within 24 h after imlifidase treatment. Donor-specific antibodies most often rebounded 3–14 d postimlifidase dose, with substantial interpatient variability. Patient survival was 100% with graft survival of 88.9% at 6 mo. With this, 38.9% had early biopsy proven antibody–mediated rejection with onset 2–19 d posttransplantation. Serum IgG levels began to normalize after ~3–7 d posttransplantation. Antidrug antibody levels were consistent with previous studies. Seven adverse events in 6 patients were classified as possibly or probably related to treatment and were mild-moderate in severity. Conclusions. Imlifidase was well tolerated, converted positive crossmatches to negative, and enabled patients with a median calculated panel-reactive antibody of 99.83% to undergo kidney transplantation resulting in good kidney function and graft survival at 6 mo.
Databáze: OpenAIRE
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