*Purpose: Chronic antibody mediated rejection (cAbMR) is a major cause of long-term kidney transplant (KT) loss. Traditional therapies for cAbMR have unclear efficacy with significant side effects. A recent single center case series suggested that IL-6 blockade with tocilizumab (Toci) in cABMR could stabilize renal function, improve microvascular inflammation (MVI) and reduce donor-specific antibodies. Here we report our findings with the use of toci in patients with cABMR.

*Methods: 10 adult KTs with acute allograft dysfunction and biopsy-proven cAbMR were treated with toci at ~8mg/kg/month (dose capped at 800mg). Patients were monitored for adverse events, and therapy was stopped in the setting of serious infections requiring hospitalization. 6 patients (60%) underwent post-treatment biopsies. Of these, 5 patients (50%) underwent transcriptome analysis using the molecular microscope (MMDx).

*Results: Patients (mean age: 43years) were initiated on toci at a median of 36 months post-KT. A majority of patients were African-American (70%), re-grafts (40%), and sensitized (mean cPRA=41%) at transplant. Eight (80%) patients had a history of prior acute ABMR. Patients received a median of 6 doses of toci (range=3-10). At a median follow-up of 12 months (range=8-24), renal function did not show improvement (mean eGFR: 42±18ml/min/1.73m2 to 37±24ml/min/1.73m2; p=0.274) and proteinuria (mean: 1.6±1.1 mg/mg to 1.9±2.3 mg/mg; p=0.70). The slope of decline in eGFR remained unchanged before and after treatment (-0.14±0.9 to -0.33±1.1; p=0.25). There was no improvement in histologic mean MVI (g+ptc) (4.8±1.4 to 4.2±2.0; p=0.39) scores or MMDx based rejection scores (0.83±0.15 to 0.79±0.15; p=0.51), and AbMR scores (0.79±0.17 to 0.78±0.26; p=0.86). There was a numerical worsening of histologic chronicity (CI+CT) scores (2.5±0.8 to 3.3±1.7; p=0.38) as well as MMDx atrophy-fibrosis scores (0.36±0.24 to 0.58±0.15; p=0.21). Patient survival was 90%, with one patient death due to complications from a hip infection. Overall death-censored graft survival was 80%, with two graft losses due to continued decline in kidney function. Both patients who lost their graft had recurrent infections requiring hospitalization. Two additional patients discontinued toci early (after 3 and 5 doses, respectively) due to infectious complications.

*Conclusions: In this early experience, we report a lack of efficacy and significant toxicity with the use of tocilizumab for cAbMR. The lack of effect could be due to patient selection, inadequate duration of therapy or increased allosensitization due to infections noted in our study. Further prospective clinical trials are needed to clarify the role of IL-6 blockade in the treatment of cAbMR.

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