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

Abstract

Background: This study aimed to gather data on physical activity (PA), bleeding, health-related quality of life, and health status, using a wearable device and an electronic patient-reported outcome (ePRO) app, in individuals with moderate or severe hemophilia A (HA) without inhibitors receiving treatment according to the clinical practice. Methods: This is a 12-month multicenter cohort study conducted in Italy. The primary outcomes included the description of PA by type and intensity, adherence to World Health Organization guidelines, bleeding, and health-related quality of life by EQ-5D questionnaire. PA data were collected continuously through a fitness tracker worn by the patient; all the other variables were collected through ePRO questionnaires. Results: Only 54 of the 103 enrolled subjects (52.4%) used their fitness tracker for the defined valid period; adolescents were the least compliant age group. PA was performed at low rates and intensity. Approximately 52% of the subjects had sedentary behavior. The mean EQ-5D values did not change over time. At least one bleeding was reported in 43.7% of the subjects, mostly with sedentary behavior. The PA in the 2 days preceding the bleeding was comparable to the one observed in the overall observational period. Conclusions: The systematic recording of data through a fitness tracker and ePRO app shows that subjects with HA without inhibitors have lower-than-expected PA and that they still experience issues related to bleeding.

Keywords: activity; bleeding; cohort studies; congenital; factor VIII deficiency; hemophilia A; pain; patient outcome; physical; quality of life.

Figure A1

Legend—N is the number of subjects in the ITT population at each time point; n is the number of subjects in the ITT population for which the value is collected at each time point. Percentages are calculated on the number of subjects for which the value is collected at each time point.

Figure A1

Legend—N is the number of subjects in the ITT population at each time point; n is the number of subjects in the ITT population for which the value is collected at each time point. Percentages are calculated on the number of subjects for which the value is collected at each time point.

Figure A2

Legend—The joint health status was collected every 6 months. For subjects who switched to any newly approved drug for hemophilia during the observational period, data were also collected 6 months after the start of the administration of the new drug. N is the number of subjects in the ITT population who completed the specific observational visit; n is the number of subjects in the ITT population for which the value was collected.

Figure A3

Legend—N is the number of subjects in each period; n is the number of subjects for which the value is collected at each time point. The vertical dashed lines define the two lockdown periods: the first period from 1 March 2020 to 4 May 2020, and the second period from 13 October 2020 to 31 December 2020. Data are summarized within each month by using the mean (blue markers in the graph). Data collected from 1 May 2020 to 4 May 2020 are summarized under April 2020. The blue line connects the means observed each month. The red line represents the estimated trend by using the Loess regression.

Figure A3

Legend—N is the number of subjects in each period; n is the number of subjects for which the value is collected at each time point. The vertical dashed lines define the two lockdown periods: the first period from 1 March 2020 to 4 May 2020, and the second period from 13 October 2020 to 31 December 2020. Data are summarized within each month by using the mean (blue markers in the graph). Data collected from 1 May 2020 to 4 May 2020 are summarized under April 2020. The blue line connects the means observed each month. The red line represents the estimated trend by using the Loess regression.

Figure 1

Patient flowchart and distribution by age group.

Figure 2

Physical activity: comparison by age group—EVL population. ° are outliers. Legend—EVL population includes ITT subjects with an exposure of at least 6 months and compliance of at least 50% within the period’s first–last valid day. MVPA = moderate to vigorous physical activity. p values are calculated by comparing age groups with a Kruskal–Wallis test.

Figure 3

Metabolic equivalent of task (MET)—EVL population. ° are outliers. Legend—EVL population includes ITT subjects with an exposure of at least 6 months and compliance of at least 50% within the period’s first–last valid day. p values are calculated by comparing age groups with a Kruskal–Wallis test.

Figure 4

EQ-5D utility score by visit—ITT population. ° are outliers. Legend—N is the number of subjects in the ITT population at each time point; n is the number of subjects in the ITT population for which the value is collected at each time point. The line joins the medians. The diamonds represent the mean.

Figure 5

EQ-EQ VAS Score by visit—ITT population. ° are outliers. Legend—N is the number of subjects in the ITT population at each time point; n is the number of subjects in the ITT population for which the value is collected at each time point. The line joins the medians. The diamonds represent the mean.

Figure 6

Adherence to the WHO guidelines for physical activity—EVL population. Legend—EVL population includes ITT subjects with an exposure of at least 6 months and compliance of at least 50% within the period’s first–last valid day. A subject was defined as “adherent” to WHO guidelines according to the following algorithm: 12–17 years old: MVPA (moderate to vigorous physical activity) minutes per day ≥ 60 min; 18–50 years old: fairly active (moderate) minutes per week ≥ 150 min OR very active (vigorous) minutes per week ≥ 75 min OR an equivalent combination of fairly and very active minutes (i.e., considering 1 fairly active minute as 0.5 very active minutes). p values are calculated by comparing age groups with a Kruskal–Wallis test.