Surgical outcomes in patients with haemophilia A or B receiving extended half‐life recombinant factor VIII and IX Fc fusion proteins: Real‐world experience in the Nordic countries

Abstract

Introduction Perioperative dosing recommendations vary across Nordic haemophilia treatment centres (HTCs) for extended half‐life (EHL) factor concentrates in haemophilia A/B (HA/HB) patients. Aim To summarise Nordic real‐world surgical experiences with EHL recombinant factor VIII/IX Fc (rFVIIIFc/rFIXFc) fusion proteins using retrospective data from clinical records at four HTCs in Finland, Sweden and Norway. Methods Factor dosing and surgical outcomes were recorded from HA/HB patients who underwent surgery and were treated with rFVIIIFc/rFIXFc. Perioperative factor dosing regimens were clinician‐determined based on local practises. Results Twenty five surgeries were performed on 20 patients, all covered by bolus injections except one minor HA surgery; eight minor surgeries were in paediatric patients. Median preoperative rFVIIIFc dose for major HA surgeries (n = 8) was 48 IU/kg (range: 35–57), with total consumption up to Day 14 of 427 IU/kg (196–568). For the two major HB surgeries (in one patient), preoperative rFIXFc doses were 50 IU/kg and 20 IU/kg; total consumption up to Day 14 was 130 IU/kg and 40 IU/kg. Median preoperative rFVIIIFc/rFIXFc bolus doses for minor HA (n = 10) and HB (n = 4) surgeries were 50 IU/kg (24–79) and 47 IU/kg (40–71), with total consumption up to Day 5 of 138 IU/kg (49–404) and 100 IU/kg (43–125), respectively. Intraoperative and postoperative haemostatic responses were rated as at least good/excellent for 24/25 surgeries, with bleeding episodes reported in only three surgeries. Conclusion Nordic real‐world experiences suggest that EHL products can be used safely and effectively for peri‐operative haemostasis. Further research is required to develop local dosing guidelines for optimised treatment schedules.

Managing surgery in hemophilia with recombinant factor VIII Fc and factor IX Fc: Data on safety and effectiveness from phase 3 pivotal studies

“…Real‐world surveillance data from more than 7 years post‐marketing experience 10,11 confirms the risk–benefit profile of rFVIIIFc and rFIXFc established during clinical studies and further underlines the potential for their perioperative use 7,58–64 . An intraindividual comparison of FIX products for orthopedic surgery showed a reduction in number of injections and total factor consumption with rFIXFc versus plasma‐derived FIX 7 .…”

“…[35][36][37][38][39][40] Real-world surveillance data from more than 7 years postmarketing experience 10,11 confirms the risk-benefit profile of rFVIIIFc and rFIXFc established during clinical studies and further underlines the potential for their perioperative use. 7,[58][59][60][61][62][63][64] An intraindividual comparison of FIX products for orthopedic surgery showed a reduction in number of injections and total factor consumption with rFIXFc versus plasma-derived FIX. 7 Similarly, an analysis of 21 subjects with hemophilia A who underwent major surgery with rFVIIIFc at a single center (provided through the WFH humanitarian aid program) demonstrated a lower median total factor consumption with rFVIIIFc during the surgical period than previously reported for SHL products.…”

Real‐world evidence on efmoroctocog alfa in patients with haemophilia A: A systematic literature review of treatment experience in Europe

“…Among the 46 identified publications, 38 were only available as abstracts, 11–48 and eight were published as full articles 49–56 . The two publications by Van der Sluijs et al 36,55 .…”

“…Study populations ranged from 3 to 290 patients. Thirty three of the identified publications did not specify whether the study population included children, adolescents or adults 11–13,15–22,25,26,30,31,33–37,39,41–48,53–56 . Of the remaining, three publications only included children, 32,40,51 one publication only included adolescents, 14 three publications only included adults, 38,49,52 and six publications included a combination of children, adolescents and adults 23,24,27–29,50 .…”

“…Of the remaining, three publications only included children, 32,40,51 one publication only included adolescents, 14 three publications only included adults, 38,49,52 and six publications included a combination of children, adolescents and adults 23,24,27–29,50 . Most publications included previously treated patients 11–14,17–19,22–25,27,28,30–37,41–43,45,46,48–55 and patients with severe haemophilia A 11,14,15,17,18,20–23,25–27,29,31,33–35,40,41,43,45–47,49–54,56 . If most of the patient population had severe haemophilia A (set to ≥80%), the study was considered a subgroup analysis of severe haemophilia A patients in the current literature review.…”