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Prophylaxis with a recombinant factor VIII Fc in hemophilia A: long-term follow-up on joint health, efficacy, and safety from phase 3 studies in children and adults.

Research and practice in thrombosis and haemostasis

Authors: Barbara A Konkle, Johannes Oldenburg, John Pasi, Roshni Kulkarni, Beatrice Nolan, Johnny Mahlangu, Guy Young, Simon A Brown, Ingrid Pabinger, Amy Shapiro, Claude Négrier, Victor Blanchette, Margaret V Ragni, Jennifer Dumont, Stefan Lethagen

BACKGROUND: Recurrent joint bleeds are a major cause of morbidity in severe hemophilia. Prophylaxis with efmoroctocog alfa (a recombinant factor VIII Fc fusion protein, [rFVIIIFc]) has demonstrated benefits beyond bleed control, including joint health maintenance.

OBJECTIVES: To assess long-term efficacy and safety of rFVIIIFc prophylaxis in severe hemophilia A in phase 3 pivotal (A-LONG/Kids A-LONG) and extension (ASPIRE) studies.

METHODS: Longitudinal analysis included pooled data from A-LONG/Kids A-LONG and ASPIRE. Subgroup analyses investigated outcomes in modified Hemophilia Joint Health Score or Hemophilia Joint Health Score and target joints in subjects with 4 to 5 years follow-up on individualized prophylaxis (IP), and those with the highest annualized bleeding rate (ABR) quartile during Year 1 of IP.

RESULTS: Overall, rFVIIIFc consumption remained stable and low ABRs were maintained, with a median treatment duration of 4.2/3.4 years in subjects from A-LONG/Kids A-LONG, respectively. Median overall ABR also remained low (1.0-2.0) in subjects on IP for 4 to 5 years. Sustained improvements in modified Hemophilia Joint Health Score or Hemophilia Joint Health Score were demonstrated over a median follow-up of 3.7 years. In subjects from A-LONG/Kids A-LONG, 99.6% ( = 234)/100% ( = 9) of evaluable baseline target joints were resolved, with no recurrence in 95%/100% of target joints. In IP subjects within the highest ABR quartile in Year 1, continued improvements were observed over a median follow-up of 4.3 years in ABR and joint health, without increased factor consumption. No inhibitors or treatment-related serious adverse events were reported.

CONCLUSION: Previously treated subjects of all ages receiving long-term prophylaxis with rFVIIIFc had sustained clinical benefits, including improved joint health and low ABR.

© 2023 The Author(s).

PMID: 37753224

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