Mapi Publications

Impact of severe haemophilia A on patients’ health status: results from the guardian™ 1 clinical trial of turoctocog alfa (NovoEight®).

Haemophilia and its treatment interfere with patients' life and may affect adherence to treatment. This study explored the impact of severe haemophilia A on patients' health status, especially in young adults (YA), using data from guardian™ 1, a multinational, open-label, non-controlled phase 3 trial investigating safety and efficacy of turoctocog alfa (NovoEight®) in previously treated patients aged 12 years and older with severe haemophilia A (FVIII ≤ 1%). Health status was assessed using the EuroQoL-5 dimensions (EQ-5D-3L), covering 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort and anxiety/depression), and a visual analogue scale (VAS) measuring self-rated overall health status. EQ-5D was administered pretreatment (screening/baseline) and posttreatment (end-of-trial). Baseline responses to the EQ-5D dimensions and VAS were described overall and by age and compared to reference values from UK general population. Guardian™ 1 included 150 patients (16 adolescents, 83 YA aged 16–29 and 51 adults aged 30+). All five dimensions of patients' health status were impacted at baseline. The percentage of haemophilia patients reporting problems was consistently significantly greater than age-matched general population reference values. Likewise, for all age groups mean baseline EQ-5D VAS score was significantly lower for haemophilia patients (YA: 78.0) than for the general population (YA aged 18–29: 87.3). The health status of patients with severe haemophilia A entering guardian™ 1 was markedly poorer than that of the general population, particularly regarding mobility and pain. YA patients reported better health status than older patients, but considerably lower than that of the general YA population.

Haemophilia A is an X-linked hereditary bleeding disorder resulting from lack or deficiency of clotting factor VIII (FVIII), causing excessive bleeding and easy bruising. Bleeding episodes are primarily treated by replacement of the missing clotting factor with recombinant or plasma derived FVIII concentrate, either as they manifest or preventively (as a prophylaxis regimen). Since the introduction of factor replacement therapy, life expectancy and quality of life of haemophilia patients have greatly improved [1, 2]. However, treatment-related complications –including development of inhibitors to FVIII, venous access problems, infusion-related pain and interference with lifestyle associated with the time-consuming nature of the treatment – impact patients' lives and may affect adherence to treatment [3].

Despite continuing efforts to better understand the experience of patients with haemophilia [4-6], data regarding their health-related quality of life (HRQoL) and health status are still limited. Adolescence and early adulthood are critical transitional periods for patients with chronic diseases [7, 8], especially haemophilia [9, 10]. This period is a time of physical, psychological and social developmental changes, which naturally impact patients' attitudes towards their condition and its management. In addition, the functional deficits related to haemophilia may be particularly detrimental at an age when physical activity is of prime importance. Therefore, any opportunity to better understand the impact of haemophilia on patients, especially adolescents and young adults (YA), is valuable.

The objective of our analyses was to gain better insight into the impact of haemophilia on patients' health status, in particular YA, using EuroQol-5 Dimensions–3 Levels (EQ-5D-3L) data collected in guardian™ 1, a phase III trial conducted to investigate safety and efficacy of turoctocog alfa (NovoEight®, Novo Nordisk A/S, Bagsvaerd, Denmark), a new recombinant FVIII compound, in adolescent and adult patients with severe haemophilia A. The generic assessment of health status EQ-5D-3L was used in the trial to complement the findings of the haemophilia-specific HRQoL instruments (HAEMO-QOL and HEM-A-QOL) [11]. In particular, the EQ-5D-3L allows generating patient-reported outcomes data that can be compared across various populations. The first aim of these analyses was to characterize the health status of these patients and compare it with that from a sample of the general population, explore the relationship (if any) between health status and national economic wealth and investigate change in health status over the course of the trial. Secondly, we set out to explore how haemophilia A patients perceive their own health status in comparison with the societal perception of their health.

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