Measuring the impact of changing from standard half‐life (SHL) to extended half‐life (EHL) FVIII prophylaxis on health‐related quality of life (HRQoL) in boys with moderate/severe haemophilia A: Lessons learned with the CHO‐KLAT tool

Abstract

Introduction: In many countries, there is a shift from standard half-life (SHL) to extended half-life (EHL) clotting factor concentrates (CFCs).Aim: To describe the experience of switching from SHL to an EHL FVIII CFC and the impact of this on frequency of infusions, factor consumption, bleeding rates and HRQoL using the Canadian Hemophilia Kids' Life Assessment Tool (CHO-KLAT).Methods: A retrospective chart review was conducted at a single haemophilia treatment centre in 2018 that included boys (ages: 4-18 years) with moderate/severe haemophilia A, without inhibitors, who switched from a SHL to an EHL FVIII CFC in the previous 2 years and for whom HRQoL data were available. Results:The study cohort comprised 38 boys [mean (SD) age: 11.0 (3.4) years] with moderate (n = 5)/severe (n = 33) haemophilia A. The switch was associated with a 33% reduction in the number of weekly infusions from a median of 3.5 to 2.3 (P < .0001) and a 17% reduction in median FVIII consumption from 103 IU/kg/wk to 85.5 IU/kg/wk (P = .004).There was no significant change in annualized joint bleed rates or in CHO-KLAT scores. Conclusions:Despite documenting several benefits of switching to EHL FVIII (less infusions, lower factor consumption with no increase in bleeding), our study did not demonstrate any improvement in HRQoL. We conclude that either the current CHO-KLAT tool is not optimized to measure burden of treatment administration in boys with low bleed rates switching from SHL to EHL FVIII CFCs or that a reduction of 1.2 infusions/week does not result in a meaningful change in HRQoL. K E Y W O R D SCanadian Hemophilia Outcomes Kids' Life Assessment Tool (CHO-KLAT), EHL FVIII, healthrelated quality of life, pediatrics, prophylaxis, severe haemophilia A | INTRODUC TI ONRecent advances in haemophilia care include the availability of extended half-life (EHL) factor (F)VIII or FIX clotting factor concentrates (CFCs) prepared using pegylation or fusion technologies. 1,2 These new CFCs show an extension of half-life of 1.4-to 1.6-fold for EHL FVIII products and 3->5-fold for EHL FIX products.EHL CFCs were designed to allow persons with haemophilia (PWH)

Factor product utilization and health outcomes in patients with haemophilia A and B on extended half‐life concentrates: A Canadian observational study of real‐world outcomes

“…However, EHL utilization was estimated based on the initial prescribed EHL regimen, and the majority of data was derived from a single paediatric centre. Similarly, in a Canadian paediatric single‐centre retrospective study, Carcao and colleagues reported a 17% reduction in the median FVIII utilization following switching to rFVIIIFc, while maintaining a low stable ABR (1.2 vs. 1.0 pre‐ and post‐switch) 6 …”

Real-Life Pharmacokinetics of rFVIII-Fc and rFIX-Fc

“…1,2 Several studies demonstrated a reduced infusion frequency, lower clotting factor consumption (CFC), and slightly lower annual bleeding rates (ABR). [3][4][5] The objective of this study was to evaluate the impact of switching from standard half-life (SHL) products to rFVIII-Fc (Efmoroctocog alfa, Elocta) and rFIX-Fc (Eftrenonacog alfa, Alprolix) on pharmacokinetics (PK), CFC, prophylactic infusion frequency, and ABR.…”

Updating the Canadian Hemophilia Outcomes–Kids’ Life Assessment Tool (CHO‐KLAT) in the era of extended half‐life clotting factor concentrates

“…In our experience, the CHO‐KLAT v2.0 was unable able to detect significant changes in HRQoL scores in groups of boys with hemophilia on long‐term prophylaxis who switched from a SHL to an EHL FC and who had very low spontaneous bleeding rates 20 . However, improvements in HRQoL have been reported using other HRQoL tools in populations of boys who switched from SHL to EHL FCs and who had high bleeding rates at the time of the switch in product 21 .…”

“…In our experience, the CHO-KLAT v2.0 was unable able to detect significant changes in HRQoL scores in groups of boys with hemophilia on long-term prophylaxis who switched from a SHL to an EHL FC and who had very low spontaneous bleeding rates. 20 However, improvements in HRQoL have been reported using other HRQoL tools in populations of boys who switched from SHL to EHL FCs and who had high bleeding rates at the time of the switch in product. 21 To the best of our knowledge, no existing disease-specific HRQoL tools have been able to demonstrate improvement in total scores TA B L E 4 Baseline scores with domain breakdown for matched pairs of child-parent scores and comparison between those using standard half-life (SHL)and extended half-life (EHL) clotting factor replacement therapies in the absence of high bleeding rates before the switch.…”