Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2025 Jul;31(4):703-712.
doi: 10.1111/hae.70070. Epub 2025 Jun 18.

TSUBASA Study: Evaluating Association of Physical Activity and Bleeding Events in People With Haemophilia A Without Factor VIII Inhibitors Receiving Emicizumab

Kagehiro Amano  1 , Teruhisa Fujii  2 , Akihiro Sawada  3 , Azusa Nagao  4 , Chiai Nagae  5 , Masanori Nojima  6 , Nobuaki Suzuki  7 , Mika Kawano  8 , Tomomi Shimura  8 , Yoshimasa Sugao  8 , Naoto Hattori  8 , Keiji Nogami  9
Affiliations
Observational Study

TSUBASA Study: Evaluating Association of Physical Activity and Bleeding Events in People With Haemophilia A Without Factor VIII Inhibitors Receiving Emicizumab

Kagehiro Amano et al. Haemophilia. 2025 Jul.

Abstract

Background: Emicizumab is approved for routine prophylaxis, but limited data exist investigating the relationship between bleeds and exercise in people with haemophilia A (PwHA) receiving emicizumab.

Aim: To evaluate the relationship between physical activity and bleeding outcomes in Japanese PwHA receiving emicizumab prophylaxis.

Methods: This prospective, multicentre, observational study was conducted in Japanese PwHA initiating emicizumab between November 2019 and October 2021. Physical activity and bleeding events were reported using an electronic patient-reported outcomes application, while activity intensity was collected by a wearable activity tracker worn over five 8-day monitoring periods. Data on safety were recorded by investigators using electronic case report forms. Quality of life data were also collected and will be reported in a separate publication.

Results: Overall, 129 participants enrolled. Median age was 32 years (range 0-73), and 83.7% of participants had severe HA. Overall, 73 participants performed 968 exercise events, with 18.8% and 6.0% of events classified as moderate and high risk, respectively. Two (0.2%) exercise events were associated with bleeding: one basketball (moderate risk) and one fishing (low risk). In total, 137 adverse events (AEs) were reported in 62 participants. No serious AEs were emicizumab-related. The mean annualised treated bleed rate was 1.9 and 51 (39.5%) participants experienced zero bleeds during the study period (97 weeks).

Conclusion: This study suggests that PwHA receiving emicizumab prophylaxis can participate in a wide range of physical activities with minimal bleeding risk, which supports their access to the health benefits of exercise. Emicizumab remains well tolerated.

Keywords: Japan; emicizumab; exercise; haemophilia A; haemorrhage; physical activity; prospective studies.

PubMed Disclaimer

Conflict of interest statement

Kagehiro Amano has received consultancy fees from Chugai Pharmaceutical Co., Ltd; research funding from KM Biologics Co., Ltd; speaker's bureau from Chugai Pharmaceutical Co., Ltd, Sanofi S.A., Bayer AG, Takeda Pharmaceuticals Co., Ltd, Novo Nordisk A/S, CSL Behring, KM Biologics Co., Ltd, Pfizer Inc., Japan Blood Products Organization, Fujimoto Pharmaceutical Co., Ltd and is listed as an entity's board of directors or advisory committee member for Chugai Pharmaceutical Co., Ltd and CSL Behring. Teruhisa Fujii has received consultancy fees from Chugai Pharmaceutical Co., Ltd, Novo Nordisk A/S, Sanofi S.A., Takeda Pharmaceuticals Co., Ltd; speaker's bureau from Chugai Pharmaceutical Co., Ltd, Novo Nordisk A/S, Sanofi S.A., Takeda Pharmaceuticals Co., Ltd, CSL Behring, Fujimoto Pharmaceutical Co., Ltd, Bayer AG, JB Pharma, JMB Pharmaceuticals, ViiV Healthcare, Gilead Sciences, Inc.; research funding from Chugai Pharmaceutical Co., Ltd and is listed as an entity's board of directors or advisory committee member for Novo Nordisk A/S. Akihiro Sawada honoraria: Chugai Pharmaceutical Co., Ltd, Takeda Pharmaceutical Co., Ltd, Sanofi K.K., Novo Nordisk A/S, CSL Behring K.K., Fujimoto Pharmaceutical Co., Ltd and KM Biologics Co., Ltd. Azusa Nagao has received consultancy fees from Chugai Pharmaceutical Co., Ltd and KM Biologics Co., Ltd; research funding from Bayer Yakuhin Ltd, Pfizer Japan Inc., Chugai Pharmaceutical Co., Ltd; honoraria from Sanofi K.K., Takeda Pharmaceuticals Co., Ltd, Chugai Pharmaceutical Co., Ltd, Bayer Yakuhin Ltd, Fujimoto Pharmaceutical Co., Ltd, KM Biologics Co., Ltd, Pfizer Japan Inc., Novo Nordisk A/S, CSL Behring and is listed as an entity's board of directors or advisory committee member for the Japanese Society of Thrombosis and Haemostasis and the International Society of Thrombosis and Haemostasis. Chiai Nagae has received honoraria from Chugai Pharmaceutical Co., Ltd, Novo Nordisk A/S, Sanofi S.A. and Takeda Pharmaceuticals Co., Ltd. Masanori Nojima has received consultancy fees from Chugai Pharmaceutical Co., Ltd and honoraria from EA Pharma Co., Ltd. Nobuaki Suzuki has received honoraria from Chugai Pharmaceutical Co., Ltd, Takeda Pharmaceuticals Co., Ltd, Sanofi S.A., Novo Nordisk A/S, CSL Behring, Bayer Yakuhin Ltd, Pfizer Inc., KM Biologics Co., Ltd and Japan Blood Products Organization. Mika Kawano, Tomomi Shimura, Yoshimasa Sugao and Naoto Hattori are employees and shareholders of Chugai Pharmaceutical Co., Ltd. Keiji Nogami has received research funding and honoraria from Chugai Pharmaceutical Co., Ltd, Sysmex Co., Takeda Pharmaceuticals Co., Ltd, Sanofi S.A., CSL Behring, KM Biologics Co., Ltd, Novo Nordisk A/S, Bayer AG, Fujimoto Pharmaceutical Co., Ltd and Sekisui Medical Co., Ltd.

Figures

FIGURE 1
FIGURE 1
Median activity intensity during exercise based on a wearable activity monitor, split by: (A) haemophilia severity, (B) target joint status and (C) emicizumab dosing regimen. The horizontal line inside each box reflects the median, and the top and bottom of each box represent Q3 and Q1, respectively. The outstretched vertical lines extend to the maximum and minimum values. HA, haemophilia A; METs, metabolic equivalent of task; Q2W, every 2 weeks; Q4W, every 4 weeks; QW, every week.
FIGURE 2
FIGURE 2
Proportion of participants receiving non‐emicizumab haemostatic agents and the reported purpose of these doses over the study duration.
FIGURE 3
FIGURE 3
Bleeding outcomes on study split by haemophilia severity, including (A) mean ABRs for treated bleeds and (B) proportion of participants with zero treated bleeds. ABR, annualised bleeding rate; HA, haemophilia A; SD, standard deviation.
See this image and copyright information in PMC

References

    1. Fromme A., Dreeskamp K., Pollmann H., Thorwesten L., Mooren F. C., and Völker K., “Participation in Sports and Physical Activity of Haemophilia Patients,” Haemophilia 13, no. 3 (2007): 323–327. - PubMed
    1. Souza J. C., Simoes H. G., Campbell C. S., Pontes F. L., Boullosa D. A., and Prestes J., “Haemophilia and Exercise,” International Journal of Sports Medicine 33, no. 2 (2012): 83–88. - PubMed
    1. Srivastava A., Santagostino E., Dougall A., et al., “WFH Guidelines for the Management of Hemophilia, 3rd Edition,” Haemophilia 26, no. suppl. 6 (2020): 1–158. - PubMed
    1. Wang M., Álvarez‐Román M. T., Chowdary P., Quon D. V., and Schafer K., “Physical Activity in Individuals With Haemophilia and Experience With Recombinant Factor VIII Fc Fusion Protein and Recombinant Factor IX Fc Fusion Protein for the Treatment of Active Patients: A Literature Review and Case Reports,” Blood Coagulation & Fibrinolysis 27, no. 7 (2016): 737–744. - PMC - PubMed
    1. Gualtierotti R., Solimeno L. P., and Peyvandi F., “Hemophilic Arthropathy: Current Knowledge and Future Perspectives,” Journal of Thrombosis and Haemostasis 19, no. 9 (2021): 2112–2121. - PMC - PubMed

Publication types

MeSH terms