BACKGROUND: Antibody mediated rejection (ABMR) accounts for 20-30% of acute rejection episodes and can affect long-term renal allograft survival. The complement system plays an active role in ABMR. Eculizumab is a humanized monoclonal antibody that selectively targets the complement cascade, inhibiting the conversion of C5 to C5b, thereby decreasing the formation of membrane attack complex. We report the largest case-series to date, evaluating eculizumab for the treatment of ABMR.

METHODS: A total of 10 adult kidney transplant recipients (4 deceased donors, 6 living donors) received eculizumab for the treatment of ABMR between January 1, 2012 and Septemper 30, 2016. Medical record data was collected on allograft function at baseline, upon receipt of each dose of eculizumab, and roughly 7-, 30-, and 90-days post treatment. Outcomes assessed included change in allograft function as measured by serum creatinine (Scr), kidney biopsy pathology, donor specific antibody changes, allograft survival, and adverse events.

RESULTS: The average time from transplant to histologic diagnosis was 121 days. Nine of 10 patients (90%) had positivity for C4d staining. Each patient received an average total eculizumab dose of 2610±1281 mg, over approximately 2.7±1.4 doses. The average baseline Scr at the time of diagnosis was 5.62±3.98 mg/dL, and decreased to 2.23±1.0 mg/dL (p=0.018), 2.06±0.95 mg/dL (p=0.013), and 1.69±0.58 mg/dL (p=0.006) at 7-, 30-, and 90-days post-treatment respectively. Clinical resolution of ABMR (defined as a decrease in the post-treatment Scr to within 25% of the lowest post-transplant Scr) or lack of ABMR on subsequent biopsy was seen in 10 out of 10 (100%) patients who received eculizumab. It took an average of 25.3±15.7 days for the Scr to decrease to within 25% of the lowest baseline reading. All patients received meningococcal vaccination at least 2 weeks before or were vaccinated and started on oral antibiotic prophylaxis just prior to initiation of eculizumab. No patients developed meningococcal infection post-treatment.

CONCLUSION: Eculizumab was effective in the treatment of 10 patients with ABMR based on clinical and/or histologic response. Meningococcal infection was prevented with vaccination and/or antibiotic prophylaxis. Larger studies are needed to further assess the place for eculizumab therapy amongst alternative ABMR treatment modalities.

CITATION INFORMATION: Chi A., Phillips J., Quan D. Eculizumab for the Treatment of Antibody Mediated Rejection in Kidney Transplant Recipients: A Single Center Experience Am J Transplant. 2017;17 (suppl 3).

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