Prophylaxis with recombinant factor IX Fc fusion protein reduces the risk of bleeding and delays time to first spontaneous bleed event in previously untreated patients with haemophilia B: A post hoc analysis of the PUPs B‐LONG study

• Published in: European journal of haematology Vol. 113; no. 4; pp. 485 - 492
• Main Authors: Nolan, Beatrice, Recht, Michael, Rendo, Pablo, Falk, Aletta, Foster, Meredith, Casiano, Sandra, Rauch, Antoine, Shapiro, Amy
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.10.2024
• Subjects: Adolescent; Bleeding; Child; Child, Preschool; Coagulation factors; Disease prevention; Factor IX - administration & dosage; Factor IX - therapeutic use; Factor IX deficiency; factor IX Fc fusion protein; Fc receptors; Female; Fusion protein; haemophilia B; Hemophilia; Hemophilia B - complications; Hemophilia B - drug therapy; Hemorrhage - etiology; Hemorrhage - prevention & control; Humans; Immunoglobulin Fc Fragments - administration & dosage; Immunoglobulin Fc Fragments - therapeutic use; Infant; Juveniles; Male; paediatric; Patients; Pediatrics; Prophylaxis; Recombinant Fusion Proteins - administration & dosage; Recombinant Fusion Proteins - therapeutic use; Treatment Outcome; haemophilia B; factor IX Fc fusion protein; factor IX deficiency; prophylaxis; paediatric
• ISSN: 0902-4441; 1600-0609; 1600-0609
• DOI: 10.1111/ejh.14252

Objectives Haemophilia B (HB), characterised by deficient factor IX (FIX), leads to spontaneous bleeds. Severe cases require prophylactic FIX replacement. This post hoc analysis assessed the first spontaneous bleeds among previously untreated patients (PUPs) with HB treated with recombinant FIX Fc fusion protein (rFIXFc) (NCT02234310) to identify factors influencing bleeds. Methods Subjects included paediatric PUPs with HB (≤2 IU/dL endogenous FIX). Analyses described treatment patterns (on demand [OD] vs. prophylaxis) and prophylaxis type (started on vs. switched to prophylaxis). Kaplan–Meier analyses assessed the time to first spontaneous bleed, including median time to event and fitting models with predictors for treatment regimen and/or baseline age. Results PUPs B‐LONG enrolled 33 subjects. Baseline age did not influence the time to first spontaneous bleed for any rFIXFc regimen. Those who started on prophylaxis with rFIXFc (n = 11), compared with those treated OD (n = 22), had an extended time to first spontaneous bleed. Starting prophylaxis afforded a 93% reduced risk of first spontaneous bleed versus starting OD (hazard ratio [95% confidence interval]: 0.071 [0.009–0.592]) (p = .015). Conclusion rFIXFc prophylaxis, particularly starting early, reduced the risk of bleeding and delayed time to first spontaneous bleed compared with rFIXFc OD. Hence, initial treatment regimens impact bleed patterns in paediatric PUPs.