Tocilizumab Treatment for Microvascular Inflammation and Chronic Active Antibody-mediated Rejection in Kidney Transplantation.

Background: Interleukin-6 (IL-6) is an important driver of humoral immunity and a target for treatment of antibody-mediated rejection (AMR) in kidney transplantation. Data on IL-6 inhibition for treatment of AMR are mixed and their efficacy remains inconclusive. In this retrospective observational study, we investigated the association of monthly tocilizumab infusions with the trajectory of estimated glomerular filtration rate (eGFR) among kidney transplant patients with histologic features of chronic active AMR. Methods: Through institutional database review, 85 adult kidney transplant patients with histologic features of chronic active AMR treated with monthly tocilizumab 8 mg/kg intravenous infusions were identified. Piecewise linear mixed effects models were fitted to compare eGFR trajectories 12 mo before and after tocilizumab initiation. Results: The eGFR declined at a rate of -0.70 mL/min/1.73 m2/mo (95% confidence interval, -1.03 to -0.36) preceding tocilizumab initiation and stabilized after treatment onset to a slope of -0.07 (-0.35 to 0.21) mL/min/1.73 m2/mo (slope difference: 0.59 [0.22-0.97] mL/min/1.73 m2/mo, P = 0.002).The distribution of the sum mean fluorescence intensity of donor specific antibodies (DSA) among 65 DSA+ patients remained unchanged from baseline to 1 y after treatment; however, 14 of 65 DSA+ patients (22%) no longer had DSA at 1 y. There was 1 graft loss and 2 deaths, both COVID-19-related, by 12 mo after treatment onset. Conclusions: This study suggests that monthly treatment with the anti-IL-6 receptor monoclonal antibody, tocilizumab, may stabilize allograft function among kidney transplant patients with chronic active AMR and that further studies to confirm its efficacy should be conducted.