Efficacy, safety and surgical management with concizumab prophylaxis in three young patients affected by severe hemophilia with inhibitors

Background: concizumab is an anti-tissue factor inhibitor monoclonal antibody designed as a once-daily subcutaneous prophylactic treatment for all hemophilia patients. The efficacy and safety of concizumab have been documented in the Explorer research program. Objectives: we describe the management and clinical outcomes of 3 subjects treated with concizumab in the phase 3 Explorer 7 trial, in which patients with hemophilia A/B with inhibitors (HAPwI/HBPwI) were enrolled. Methods: in 3 subjects (1 HAPwI and 2 HBPwI) followed in our Centre and enrolled in Explorer 7 trial the following data were collected: diagnosis, age at switch to concizumab, pre-switch antihemorrhagic treatment, venous access, joint involvement, bleeding events in the 6 months before switch, comorbidity, medications, quality of life (QoL), physical activity, date of switch and following bleeding events, treatment with recombinant activated factor VII (rFVIIa), surgery, QoL, physical activity. Results: during the 5 years following the switch to concizumab all the patients had a drastic reduction in bleeding events and therefore of treatment with rFVIIa. A significant improvement in QoL, both in relation to pain reduction, movement ability and autonomy from caregivers, was achieved. No side effects were observed, and the management of 1 major and 14 minor surgeries did not present any bleeding or thrombotic complications. Conclusions: concizumab represents a unique opportunity for HBPwI, but it may be of extreme value also for HAPwI. In our cases concizumab demonstrates and confirms clinical efficacy, positive impact on QoL and safety even in surgical settings.