Stephen, Jenise

Introduction: Eculizumab is a monoclonal antibody that binds to complement protein C5, inhibiting complement-mediated thrombotic microangiopathy. It is approved for several indications including atypical hemolytic uremic syndrome. Additionally, eculizumab is used off-label for antibody-mediated rejection and C3 glomerulopathy in renal transplant recipients. Due to limited data available, the purpose of this study was to describe the use of eculizumab treatment in renal transplant recipients. Design: This retrospective single-center study evaluated the safety and efficacy of eculizumab for on- and off-label indications in renal transplant recipients. Adult renal transplant recipients receiving at least 1 dose of eculizumab posttransplant between October 2018 and September 2021 were included. The primary outcome evaluated was graft failure in patients treated with eculizumab. Results: Forty-seven patients were included in analysis. The median age at eculizumab initiation was 51 years [IQR 38-60], with 55% being female. Indications for eculizumab included atypical hemolytic uremic syndrome/thrombotic microangiopathy (63.8%), antibody-mediated rejection (27.7%), C3 glomerulopathy (4.3%), and other (4.3%). Graft failure occurred in 10 patients (21.3%) with a median of 2.4 weeks [IQR 0.5-23.3] from transplant to graft failure. At last follow-up (median 56.1 weeks), 44 (93.6%) patients were alive. After eculizumab initiation, renal function improved at 1 week, 1 month, and last follow-up. Conclusion: Eculizumab treatment demonstrated a benefit on graft and patient survival compared to reported incidence in thrombotic microangiopathy and antibody-mediated rejection. Due to the small sample size and retrospective design, further research is warranted to confirm these results.

Abstract Background Eculizumab, an inhibitor of terminal complement activation, has been utilized in pre-transplant desensitization, treatment of antibody-mediated rejection and thrombotic microangiopathy in solid organ transplant recipients (SOTR). Eculizumab is associated with meningococcal disease, leading to guidelines for vaccination against serogroups ACWY (menACWY) and B (menB) at least 2 weeks prior to eculizumab therapy. In persons requiring emergent use of eculizumab, prophylaxis for at least 2 weeks is recommended. SOTRs respond suboptimally to vaccination, raising consideration for pre-transplant vaccination and prolonged prophylaxis in those undergoing eculizumab therapy. We sought to describe meningococcal vaccination and prophylaxis practices among SOTRs receiving eculizumab. Methods We performed a retrospective chart review of meningococcal vaccination, including number and timing pre- or post-transplant, along with prophylaxis prescribing and duration in SOTRs receiving eculizumab across 3 distinct Mayo Clinic Enterprise sites (Rochester, Arizona, and Florida). Results 200 SOTRs receiving at least one dose of eculizumab between 1/1/2008 and 9/16/2021 were reviewed. Eculizumab indications included antibody mediated rejection (38%), desensitization (26%), and thrombotic microangiopathy (19%). 83% (166/200) of SOTRs received eculizumab for an unanticipated post-transplant complication. Vaccination rates were 82% (164/200) and 35.5% (71/200) for menACWY dose 1 and 2, respectively, and 54% (108/200) and 28.5% (57/200) for menB dose 1 and 2, respectively. The majority received their first vaccination post-transplant: menACWY 66.5% (133/200) and menB 2.5% (185/200). Among those without vaccination pre-eculizumab, 22.3% (41/184) were not prescribed prophylaxis. The median duration of prophylaxis was 62 (range 4-2651) days. Conclusion Most SOTRs underwent meningococcal vaccinations near the time of eculizumab administration post-transplant for an unanticipated complication. One-fifth of those meeting criteria were not provided meningococcal prophylaxis. These findings may support pre-transplant administration of meningococcal vaccinations and heightened awareness for meningococcal prophylaxis in SOTRs receiving eculizumab. Disclosures All Authors: No reported disclosures.