Does tocilizumab improve clinical outcomes and demonstrate safety in adult heart transplant recipients with chronic, treatment-refractory antibody-mediated rejection?
Tocilizumab appears safe and well-tolerated in a very small case series of heart transplant recipients with refractory chronic antibody-mediated rejection, with potential signals of clinical improvement requiring further study.
BACKGROUND Chronic antibody-mediated rejection (AMR) after heart transplantation is associated with progressive graft dysfunction and increased mortality, and effective treatment options remain limited. Interleukin-6 (IL-6) inhibition with tocilizumab has emerged as a potential therapeutic strategy, although evidence in cardiac transplantation is scarce and limited to small case series. OBJECTIVE To describe the safety and clinical course of heart transplant recipients with chronic, treatment-refractory AMR treated with tocilizumab. METHODS This retrospective case series included 2 adult heart transplant recipients with biopsy-proven chronic AMR refractory to plasmapheresis, intravenous immunoglobulin, and rituximab. Tocilizumab was administered intravenously at a dose of 8 mg/kg monthly for 6 months. Clinical outcomes, laboratory parameters, immunologic data, and echocardiographic findings were assessed before and after treatment (March-September 2024). RESULTS Both patients completed 6 doses of tocilizumab. No serious adverse events occurred; 1 patient developed a single episode of transient febrile neutropenia. No infections, bleeding events, or clinically significant hepatic enzyme elevations were observed. Unplanned hospitalizations for heart failure decreased during treatment, and both patients reported subjective improvement in functional status (NYHA class III-II). No consistent reduction in donor-specific HLA antibody mean fluorescence intensity was observed. Left ventricular ejection fraction remained stable, while global longitudinal strain improved in 1 patient. CONCLUSION In this small case series, tocilizumab was safe and well tolerated in heart transplant recipients with chronic refractory AMR. Although clinical improvement was observed, the extremely limited sample size precludes conclusions regarding efficacy. Larger, prospective studies are required to clarify the role of IL-6 inhibition in chronic cardiac AMR.
Sánchez et al. (Sun,) studied this question.