Tocilizumab and desensitization in kidney transplant candidates: Personal experience and literature review

Abstract

Desensitization (DES) allows kidney transplantation for highly HLA‐sensitized subjects. Due to the central role of IL‐6 in the immunological response, tocilizumab may improve DES efficacy. Thus, we conducted a PubMed systematic review using the MeSH terms tocilizumab, interleukin‐6, kidney transplantation, and desensitization. Tocilizumab (TCZ) was first studied for DES as the second‐line treatment after failure of a standard DES protocol (SP) (apheresis, rituximab +/‐ IVIg). Although TCZ (as a monotherapy) attenuated anti‐HLA antibody rates, it did not permit transplantation. However, lymphocyte immuno‐phenotyping has shown that TCZ hinders B‐cell maturation and thus could improve the long‐term efficacy of DES by limiting anti‐HLA rebound and so avoid antibody‐mediated rejection. This hypothesis is supported by a recent study where clazakizumab, a monoclonal antibody directed against IL‐6, was continued after kidney transplantation in association with an SP. Nine out of ten patients were then eligible for transplantation, and there were no donor‐specific antibodies at 6 months post‐transplantation. In association with an SP, tocilizumab does not seem to significantly improve kidney‐allograft access (short‐term efficacy) vs. a SP only. However, it could improve the long‐term prognosis of HLA-incompatible transplantation by hindering B‐cell maturation and, thereby, avoiding donor‐specific antibody rebounds post‐transplantation.