Use of the terminal complement inhibitor eculizumab in paediatric heart transplant recipients

Abstract

Antibody-mediated rejection is a major clinical challenge that limits graft survival. Various modalities of treatment have been reported in small studies in paediatric heart recipients. A novel approach is to use complement-inhibiting agents, such as eculizumab, which inhibits cleavage of C5 to C5a thereby limiting the formation of membrane attack complex and terminal complement-mediated injury of tissue-bound antibodies. This medical modality of treatment has theoretical advantages but the collective experience in its use in the solid organ transplant community remains small. We add to this experience by combining 14 cases from 6 paediatric heart centres in this descriptive study.

Complement blockade with eculizumab to treat acute symptomatic humoral rejection after heart transplantation

“…To our best knowledge, our case report is the first detailed description of the successful use of eculizumab to treat acute cardiac AMR. It contrasts with the series reported by Law et al, where six of the 11 eculizumab‐treated pediatric heart recipients with AMR expired at a median time of 21 days 16 . Although many similitudes can be found between their series and our patient (all with DSA, most with hemodynamic compromise), there was the main difference in the timing of eculizumab initiation: a couple of hours from diagnosis in our case versus 0–23 days in Law et al.…”

“…However, the experience with eculizumab for established AMR is still preliminary and mainly restricted to refractory AMR after plasmapheresis 15 . To our best knowledge, the only report about eculizumab use is a retrospective analysis of 14 pediatric heart recipients 16 . Only 11 of them had endomyocardial biopsy (EMB) proven AMR, the remaining three receiving eculizumab for AMR prevention after HTx with a positive crossmatch.…”

Management of the Sensitized Cardiac Transplantation Recipient

“…Other novel therapies have been used; Carfilzomib, another 26S proteasome inhibitor with lesser neuropathy compared to Bortezomib has been used in a single case study in a patient who had 100% CPRA leading to successful transplantation [56]. Eculizumab, a monoclonal antibody that binds complement C5 has been used in sensitized pediatric heart transplant recipients [57] and is being studied (NCT02013037) to evaluate the efficacy in preventing AMR and cell mediated rejection in highly sensitized adult heart transplant patients.…”

Eculizumab for antibody‐mediated rejection in heart transplantation: A case‐control study

“…A novel approach is the use of complement‐inhibiting agents, such as eculizumab, which inhibits cleavage of C5 to C5a thereby limiting formation of membrane attack complex and complement‐mediated injury of tissue‐bound antibodies. Eculizumab is used in kidney transplantation for both treatment of AMR 5 and prevention 6,7 in sensitized transplant recipients, but experience in heart transplantation is limited 8–10 …”

“…7 In heart transplant recipients, experience is also limited to case series for the treatment of rejection. 8,10 However, eculizumab is used as induction therapy for highly sensitized patients with panel reactive antibodies ≥70% and pre-formed DSA. 9 When compared to matched control patients, there was a significant 64% reduction in the risk of biopsy-proven AMR in patients treated with eculizumab.…”