Physical Activity, Bleedings and Quality of Life in Patients with Haemophilia a without Inhibitors - a Multicenter, Observational Italian Study with a Wearable Device

Introduction: Haemophilia A (HA) is characterized by spontaneous or traumatic recurrent bleedings, especially in joints and muscles, which can cause haemophilic arthropathy, impaired function, and in turn, reduce physical and social activities and negatively impact the quality of life (Franchini M at al., Semin Thromb Hemost, 2022 Nov; Mannucci PM et al., N Engl J Med, 2001 Jun). Despite regular physical activity (PA) being strongly recommended by guidelines as a key element to improve well-being and mental health, the perception of an associated increased risk of bleeding and bleed-related issues discourage people with hemophilia A (PWHA) (Makris M at al, Haemophilia, 2013 Jan; Matlary RED at al., Haemophilia, 2022 Nov; Srivastava A et al., Haemophilia, 2020 Aug 1)

Methods: This cohort study (NCT04165135 - POWER) is a multicenter study conducted in 18 investigational Italian sites aimed at gathering data on activity status, bleeding, QoL, and health status, through the use of a wearable device and an ePRO app, in individuals with moderate or severe HA without inhibitors receiving standard of care (SoC) treatment. This population was observed for 12 months or up to 18 months if the therapy with a newly approved product was initiated during the study. The study started in January 2020 and has been completed in April 2022 with the last data collection.

Results: A total of 103 male patients represented the Intention To Treat Population (ITT). Of them, 97 (94.2%) had severe (FVIII <1%) and 6 (5.8%) moderate (FVIII 1-2%) HA without inhibitors. They were aged 12-50 years (17, 16.5% aged 12-17 years [adolescents]; 46, 44.7% aged 18-30 years [young], and 40, 38.8% aged 31-50 years [adults]); 21 subjects switched to a newly approved agent for HA during the study and were followed for additional six months after the switch. Eighty-eight (85%) completed the study.

The primary outcome measures included the duration and type of PA, distance covered, calories burned, body weight, heart rate, sleep data, active minutes, metabolic equivalents for tasks (METs), and step counts. The secondary measurements included the documentation of PA by type and intensity, the description of the population in terms of adherence to WHO Guidelines, disease severity, and treatment regimen for HA, health status, joint health status, and BMI.

PA data were collected continuously through a fitness tracker worn by the patient. HRQoL questionnaires, joint health assessments, intensity of pain and bleeding episodes were recorded by the patient through an ePRO app (Petracca F. at al., JMIR Form Res 2021)

Only 54/103 subjects (52.4%), which represented the Evaluable Population (EVL), were using the fitness tracker for at least 10 hours in 50% of their days for a period of at least 6 months in the study; adolescents were the least compliant age group. The fitness tracker's analysis of the type of activity collected showed low weekly rates for all activities (no differences in the different physical activities). High-intensity physical activities were poorly represented in all the subgroups. Approximately 51% of the subjects (including all adolescents) had sedentary behavior (Figure1). The mean METs per day were lower in adults. The EQ-5D utility score did not change during the observational period. The mean EQ-5D VAS progressively worsened, indicating a situation of discomfort and pain during the study. The results of HRQoL showed that a sedentary condition was associated with a worse quality of life, a higher risk of hospitalization, and a worse joint status compared to active patients. At least one bleeding (mean 2.9; median 2.0) was reported in 43.7% of the subjects (Figure 2), with a higher proportion in sedentary than active subjects. The physical activity in the 2 days preceding the bleeding was comparable to the one observed in the overall observational period. Adherence to the treatment regimen was quite poor overall (mean 55%) and only 26.2% of the subjects had an adherence ≥ 80%.

Conclusion: The results from this study show that patients with HA without inhibitors have a lower-than-expected physical activity. Despite the poor PA, around half of the subjects reported bleeds, especially in the sedentary population. This suggests that other causes than PA, such as treatment adherence and type of treatment, might affect the number, frequency, and severity of bleedings.

This study has been sponsored and financially supported by Roche Italy.