Emicizumab treatment and monitoring in a paediatric cohort: real-world data

Br J Haematol. 2020 Oct;191(2):282-290. doi: 10.1111/bjh.16964. Epub 2020 Jul 12.

Abstract

Real-world data on emicizumab use and monitoring in paediatric severe haemophilia A (HA) patients are scarce. We therefore sought to evaluate safety, efficacy, and laboratory monitoring of emicizumab prophylaxis in a cohort of 40 children with severe HA, including 22 non-inhibitor patients and nine infants younger than one year. Bleeding, trauma, adverse events, and surgeries were documented during a median follow-up of 45 weeks. Emicizumab levels, activated partial thromboplastin time (aPTT) values, and thrombin generation were measured before and during therapy. Twenty patients experienced zero bleeds. All bleeding was trauma-related, and bleeding risk was positively correlated with the length of emicizumab prophylaxis. Sixteen surgical interventions were performed in 12 patients, with no thrombotic complications or thrombotic microangiopathy. Prolonged aPTT values normalised after emicizumab initiation, correlating with an increase in emicizumab plasma levels. Elevation in the thrombin generation was observed following emicizumab prophylaxis, with lower values recorded in younger infants. Emicizumab prophylaxis was safe and well tolerated. As all bleedings were trauma-related, laboratory monitoring could not predict bleeding risk. Our results do not support routine thrombin generation monitoring in children treated by emicizumab, yet further studies are warranted in the context of surgical procedures.

Keywords: children; emicizumab; haemophilia; monitoring; thrombin-generation.

MeSH terms

  • Adolescent
  • Antibodies, Bispecific* / administration & dosage
  • Antibodies, Bispecific* / pharmacokinetics
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / pharmacokinetics
  • Child
  • Child, Preschool
  • Drug Monitoring*
  • Female
  • Follow-Up Studies
  • Hemophilia A* / blood
  • Hemophilia A* / drug therapy
  • Hemorrhage* / blood
  • Hemorrhage* / prevention & control
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Partial Thromboplastin Time

Substances

  • Antibodies, Bispecific
  • Antibodies, Monoclonal, Humanized
  • emicizumab