Lack of Efficacy and Safety of Eculizumab for Treatment of Antibody-Mediated Rejection Following Renal Transplantation
We evaluated the efficacy and safety of eculizumab in comparison with plasmapheresis and intravenous immunoglobulin therapy in renal transplant recipients diagnosed with antibody-mediated rejection (AMR).
METHODS:This was a multicenter, open-label, prospective, randomized analysis. The patients were randomized by therapy type (eg, eculizumab infusions or standard of care [SOC]: plasmapheresis/intravenous immunoglobulin). The patients (ie, eculizumab arm: 7 patients, SOC arm: 4 patients) were evaluated for the continued presence of donor-specific antibodies (DSAs) and C4d (staining on biopsy), as well as histologic evidence, using repeat renal biopsy after treatment.
RESULTS:The allograft biopsies revealed that eculizumab did not prevent the progression to transplant glomerulopathy. Only 2 patients in the SOC arm experienced rejection reversal, and no graft losses occurred in either group. After AMR treatment, the DSA titers generally decreased compared to titers taken at the time of AMR diagnosis. There were no serious adverse effects in the eculizumab arm.
CONCLUSIONS:Eculizumab alone cannot treat AMR effectively and does not prevent acute AMR from progressing to chronic AMR or transplant glomerulopathy. However, it should be considered as a potential alternative therapy because it may be associated with decreased DSA levels.
| Reviewer: | Mr John O'Callaghan, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford |
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| Conclusion: | This is a small randomised controlled trial in Antibody Mediated Rejection (AMR) of renal transplants. Patients with confirmed AMR were randomised to standard care (plasmapheresis and IVI Ig as prescribed by clinicians) or to eculizimab infusion. There were 11 patients included, so a relatively small number, but this would have been dependent on a low number of potential patients to include. The study commenced in 2013 and has only just come to publication. It is not clear that the study was adequately randomised, and there was also the possibility for patients to cross over to the other arm if treatment failed, which further confuses the results and interpretation. There was also considerable variation in additional treatments, such as the use of Campath, Basiliximab, Rituximab and ATG. The main conclusion to draw from this small study is that eculizumab alone did not reverse rejection in any case, prevent progression to chronic AMR or transplant glomerulopathy. |
| Jadad score | 1 |
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| Allocation concealment | NO |
| Data analysis | PER PROTOCOL |
| Aims: | This study aimed to compare the efficacy and safety of eculizumab versus plasmapheresis (PP) and intravenous immunoglobulin therapy (IVIG) in kidney transplant patients with antibody-mediated rejection (AMR). |
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| Interventions: | Participants were randomly assigned to receive either eculizumab or standard of care (PP combined with IVIG). |
| Participants: | 11 kidney transplant recipients between 18 and 75 years of age. |
| Outcomes: | The main outcomes of interest were as follows: mean serum creatinine, rejection reversal, graft loss and serious adverse events. |
| Follow Up: | 12 months |
| Funding: | Industry funding |
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| Publication type: | Randomized Controlled Trial, Multicenter Study, Randomised Controlled Trial |
| Organ: | Kidney |
| Language: | English |
| Author email: | 67920@naver.com |
| MeSH terms: | Humans; Kidney Transplantation; Immunoglobulins, Intravenous; Prospective Studies; Antibodies, Monoclonal, Humanized; A3 Ulp0 F556 (Eculizumab); 0 (Immunoglobulins, Intravenous); 0 (Antibodies, Monoclonal, Humanized) |