Safety, immunogenicity, pharmacokinetics, and efficacy of degradation of anti-HLA antibodies by IdeS (imlifidase) in chronic kidney disease patients.

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Lorant T, Bengtsson M, Eich T, Eriksson BM, Winstedt L, Jarnum S, Stenberg Y, Robertson AK, Mosen K, Bjorck L, Backman L, Larsson E, Wood K, Tufveson G, Kjellman C

Safety, immunogenicity, pharmacokinetics, and efficacy of degradation of anti-HLA antibodies by IdeS (imlifidase) in chronic kidney disease patients.

Am J Transplant. 2018 Nov;18(11):2752-2762. doi: 10.1111/ajt.14733. Epub 2018 Apr 17.

PubMed ID
29561066 [ View in PubMed
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Abstract

Safety, immunogenicity, pharmacokinetics, and efficacy of the IgG-degrading enzyme of Streptococcus pyogenes (IdeS [imlifidase]) were assessed in a single-center, open-label ascending-dose study in highly sensitized patients with chronic kidney disease. Eight patients with cytotoxic PRAs (median cytotoxic PRAs of 64%) at enrollment received 1 or 2 intravenous infusions of IdeS on consecutive days (0.12 mg/kg body weight x2 [n = 3]; 0.25 mg/kg x1 [n = 3], or 0.25 mg/kg x2 [n = 2]). IgG degradation was observed in all subjects after IdeS treatment, with <1% plasma IgG remaining within 48 hours and remaining low up to 7 days. Mean fluorescence intensity values of HLA class I and II reactivity were substantially reduced in all patients, and C1q binding to anti-HLA was abolished. IdeS also cleaved the IgG-type B cell receptor on CD19(+) memory B cells. Anti-IdeS antibodies developed 1 week after treatment, peaking at 2 weeks. A few hours after the second IdeS infusion, 1 patient received a deceased donor kidney offer. At enrollment, the patient had a positive serum crossmatch (HLA-B7), detected by complement-dependent cytotoxicity, flow cytometry, and multiplex bead assays. After IdeS infusion (0.12 mg/kg x2) and when the HLA-incompatible donor (HLA-B7(+) ) kidney was offered, the HLA antibody profile was negative. The kidney was transplanted successfully.

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