Plasma-derived C1 esterase inhibitor for acute antibody-mediated rejection following kidney transplantation: Results of a randomized double-blind placebo-controlled pilot study
Antibody-mediated rejection (AMR) is typically treated with plasmapheresis (PP) and intravenous immunoglobulin (standard of care; SOC); however, there is an unmet need for more effective therapy. We report a phase 2b, multicenter double-blind randomized placebo-controlled pilot study to evaluate the...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
09 May 2016
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| In: |
American journal of transplantation
Year: 2016, Volume: 16, Issue: 12, Pages: 3468-3478 |
| ISSN: | 1600-6143 |
| DOI: | 10.1111/ajt.13871 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1111/ajt.13871 Verlag, Volltext: http://onlinelibrary.wiley.com/doi/10.1111/ajt.13871/abstract 
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| Author Notes: | R.A. Montgomery, B.J. Orandi, L. Racusen, A.M. Jackson, J.M. Garonzik-Wang, T. Shah, E.S. Woodle, C. Sommerer, D. Fitts, K. Rockich, P. Zhang and M.E. Uknis |
| Summary: | Antibody-mediated rejection (AMR) is typically treated with plasmapheresis (PP) and intravenous immunoglobulin (standard of care; SOC); however, there is an unmet need for more effective therapy. We report a phase 2b, multicenter double-blind randomized placebo-controlled pilot study to evaluate the use of human plasma-derived C1 esterase inhibitor (C1 INH) as add-on therapy to SOC for AMR. Eighteen patients received 20 000 units of C1 INH or placebo (C1 INH n = 9, placebo n = 9) in divided doses every other day for 2 weeks. No discontinuations, graft losses, deaths, or study drug-related serious adverse events occurred. While the study's primary end point, a difference between groups in day 20 pathology or graft survival, was not achieved, the C1 INH group demonstrated a trend toward sustained improvement in renal function. Six-month biopsies performed in 14 subjects (C1 INH = 7, placebo = 7) showed no transplant glomerulopathy (TG) (PTC+cg≥1b) in the C1 INH group, whereas 3 of 7 placebo subjects had TG. Endogenous C1 INH measured before and after PP demonstrated decreased functional C1 INH serum concentration by 43.3% (p < 0.05) for both cohorts (C1 INH and placebo) associated with PP, although exogenous C1 INH-treated patients achieved supraphysiological levels throughout. This new finding suggests that C1 INH replacement may be useful in the treatment of AMR. |
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| Item Description: | Gesehen am 14.11.2017 |
| Physical Description: | Online Resource |
| ISSN: | 1600-6143 |
| DOI: | 10.1111/ajt.13871 |