Marginal Impact of Tocilizumab Monotherapy on Anti-HLA Alloantibodies in Highly Sensitized Kidney Transplant Candidates

Abstract

Background. Highly HLA–sensitized kidney transplant candidates are difficult to desensitize, which reduces their chances of receiving a transplant. Methods. We administered tocilizumab as a monotherapy (8 mg/kg once a mo) to 14 highly sensitized kidney transplant candidates. Highest mean fluorescence intensities of anti-HLA antibodies obtained before and after tocilizumab administration were compared from raw and diluted sera. Results. The administration of tocilizumab significantly reduced dominant anti-HLA antibody sensitization. However, this decrease in mean fluorescence intensities was minor compared with the initial values. Conclusions. Tocilizumab as a monotherapy was not sufficient to allow highly sensitized kidney–transplant candidates to undergo transplantation and, therefore, was not an effective desensitization method.

Tocilizumab and Desensitization in Kidney Transplant Candidates: Personal Experience and Literature Review

“…In order to assess the efficacy and safety of a DES protocol based exclusively on tocilizumab Daligault and our team conducted a single-center, non-randomized study in 14 highly sensitized candidates awaiting kidney transplantation who had not previously received any other DES treatment [ 46 ]. While having a favorable safety profile (only one serious adverse event of an infectious nature), there was also a significant decrease in the MFI of the immunodominant anti-HLA antibody and in the number of antibodies with MFI > 10,000.…”

Tocilizumab Trough Levels Variability in Kidney-Transplant Candidates Undergoing Desensitization

“…In addition, our results must be weighed up against the modest overall effect of TCZ as the single desensitization strategy [ 9 , 10 ]. Previous studies have suggested that the response to TCZ in rheumatoid arthritis is greater when sIL-6R levels are low [ 23 ].…”

“…The number of TCZ infusions could be extended beyond 6 months, as decided by the attending clinician. When TCZ cycles were completed, following our standard-of-care, patients received two infusions of rituximab and underwent apheresis for antibody removal until transplantation [ 9 ].…”

“…HLA antibodies were evaluated for each TCZ sample using a Single Antigen test (Immucor ® ) on a Luminex ® platform, which enabled detection of immunoglobulin G (IgG) antibodies directed against class 1 or class 2 HLA antigens [ 9 ]. The results are expressed as MFI, with a positivity threshold for clinically significant antibodies at a MFI of 3000 [ 9 ].…”

“…However, only half of these patients were able to receive a transplant (5/10 patients) and one patient developed antibody-mediated rejection after transplantation [ 5 ]. In our recently published experience, TCZ as a desensitization therapy failed to induce a clinically significant reduction in anti-HLA antibody mean fluorescent intensity (MFI) [ 9 ], but limited B-cell maturation [ 10 ].…”