Eculizumab is Associated With Increased Infection Rates and Infection Related Mortality in Children With Thrombotic Microangiopathy After HCT

Abstract

Complement C5 inhibition can be used to treat hematopoietic cell transplant-associated thrombotic microangiopathy (TA-TMA) but may impact infectious organism clearance, impeding opsonization and lysis. The infectious risks of eculizumab exposure after hematopoietic cell transplant (HCT) are unknown. In this single center, retrospective case–control study, we included allogeneic HCT recipients transplanted from January 2019 to January 2023. All patients with TA-TMA treated with eculizumab from day 14–180 post HCT were identified as cases. Controls were matched using an exact matching procedure on maximum grade 3–4 acute GVHD and intensive care unit admission. Cases and controls were matched on index date (first day of eculizumab therapy), and infections from 1 year of index date were captured. Among 31 pairs (62 patients), the rate of bacteremia was 8.49 times higher (95% CI 4.4, 16.4), tissue specific bacterial infections 6.22 times higher (95% CI 2.28, 17.17), and viral infections 3.16 times higher (95% CI 1.90, 5.25) in eculizumab exposed children compared to matched controls. After adjusting for the number of immune suppressive medications, steroid days exposed, and steroid refractory GVHD, all infection rates remained significantly higher among eculizumab exposed patients. In sensitivity models excluding an outlier and altering the study follow up time to 3 and 6 months, rates of infections remained significantly higher in the eculizumab cohort. Infection related mortality was significantly higher in the eculizumab exposed patients than controls; 1-yr mortality was 45% vs 19% respectively. This study suggests infectious complications are increased with eculizumab treatment in the HCT setting, though additional studies are needed to validate these findings.