Imlifidase desensitization in crossmatch-positive, highly-sensitized kidney transplant recipients: Results of an international phase 2 trial (Highdes)
| العنوان: | Imlifidase desensitization in crossmatch-positive, highly-sensitized kidney transplant recipients: Results of an international phase 2 trial (Highdes) |
|---|---|
| المؤلفون: | Jordan, Stanley C., Legendre, Christophe, Desai, Niraj M., Lorant, Tomas, 1975, Bengtsson, Mats, Lonze, Bonnie E., Vo, Ashley A., Runström, Anna, Laxmyr, Lena, Sjöholm, Kristoffer, Schiött, Åsa, Sonesson, Elisabeth, Wood, Kathryn, Winstedt, Lena, Kjellman, Christian, Montgomery, Robert A. |
| المصدر: | Transplantation. 105(8):1808-1817 |
| الوصف: | BACKGROUND: Highly-HLA sensitized patients have limited access to life-saving kidney transplantation due to 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 five transplant centers, evaluated the ability of imlifidase to create a negative crossmatch test within 24 hours. Secondary endpoints included post-imlifidase DSA levels compared to pre-dose levels, renal function, and pharmacokinetic/pharmacodynamic profiles. Safety endpoints included adverse events and immunogenicity profile.RESULTS: 89.5% of the transplanted patients demonstrated conversion of baseline positive crossmatch to negative within 24 hours after imlifidase treatment. DSA most often rebounded 3-14 days post-imlifidase dose, with substantial interpatient variability. Patient survival was 100% with graft survival of 88.9% at 6 months. 38.9% had early biopsy proven antibody mediated rejection with onset 2-19 days post-transplantation. Serum IgG levels began to normalize after ~3-7 days post-transplantation. Anti-drug antibody levels were consistent with previous studies. Seven adverse events in six 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 cPRA of 99.83% to undergo kidney transplantation resulting in good kidney function and graft survival at 6 months. |
| وصف الملف: | electronic |
| URL الوصول: | https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-428870 https://doi.org/10.1097/TP.0000000000003496 https://uu.diva-portal.org/smash/get/diva2:1510849/FULLTEXT01.pdf |
| قاعدة البيانات: | SwePub |
| تدمد: | 00411337 15346080 |
|---|---|
| DOI: | 10.1097/TP.0000000000003496 |