Tocilizumab Evaluation in HLA-Desensitization before Kidney Transplantation as an Add-On Therapy to Apheresis: The TETRA Study

Abstract

Background: Desensitization strategies improve access to transplantation in highly sensitized kidney transplant candidates. Tocilizumab could be a valuable addition to more traditional desensitization regimens. We investigated the effect of tocilizumab as an add-on therapy to our standard of care (SoC) desensitization strategy based on rituximab and apheresis. Methods: In this study, we prospectively included highly sensitized patients to receive monthly tocilizumab infusions for 6 months before our SoC regimen (Toci + SoC group). We compared the reductions in the mean fluorescent intensity (MFI) rebound at post-transplantation and kidney function at 1-year post-transplantation to patients treated by SoC (based on apheresis and two doses of rituximab). Results: Twenty-six patients were included in the SoC group; seven in the Toci + SoC group. Reductions in pre-transplantation MFI were similar between groups. At 1-year post-transplantation, there was no absolute difference in overall MFI rebounds, including donor-specific antibodies. Toci + SoC helped lower the rebound of antibodies with more elevated baseline MFIs. Graft function and survival rates were similar at one-year post-transplantation (median eGFR 62.8 vs. 65.6 mL/min/1.73 m2 for SoC and Toci + SoC, respectively). Conclusions: Tocilizumab as an add-on to SoC desensitization may help control the post-transplantation rebound of antibodies with elevated baseline MFIs. However, reductions in pre-transplantation MFIs were similar with or without tocilizumab. Further studies are needed to validate this pilot study.

Granulomatous Tubulointerstitial Nephritis in a Kidney Allograft: Treatment with Interleukin-6 Receptor Antagonist Stabilises Kidney Function

“…A more recent study of TCZ monotherapy for HLA-desensitisation showed discordant results; anti-HLA antibody level MFI (mean-fluorescence intensity measured by Luminex assay) values were not reduced sufficiently to allow donor-matching to proceed [ 19 ]. More recently, Jouve and colleagues found no difference in the rate of graft survival at one year for patients desensitised with TCZ in addition to IVIg and rituximab [ 21 ].…”

Preventing Rejection of the Kidney Transplant

“…Marks et al examined the use of eculizumab versus standard of care (plasmapheresis +/− IVIG) and found no significant difference in treatment failure between the two groups at 9 weeks post transplantation (9.8% vs. 13.7%, p = 0.760). A French study looked at tocilizumab (IL-6 inhibitor) in comparison to standard therapy (apheresis and Rituximab) and found no difference in reduction of pre-transplant MFIs between the groups [ 35 ].…”

Advances in desensitization for human leukocyte antigen incompatible kidney transplantation

“…MFI decrease was minor compared with the initial values; this was insufficient to allow compatible kidney transplant, with only one patient transplanted. Jouve et al [38] conducted the TETRA study where monthly TCZ × 6 months was given before SOC regimen (TCZ + SOC group) and found that TCZ added to SOC may help limit posttransplant HLA antibody rebound, but reductions in pretransplant MFIs were not clinically significant compared to SOC.…”