Paediatric Subanalysis of TSUBASA, Assessing Physical Activity, Bleeding, Quality of Life and Safety in People with Haemophilia A Receiving Emicizumab

TL;DR

This study shows that children with hemophilia A on emicizumab can safely engage in physical activity with low bleeding risk and maintained quality of life.

Contribution

Provides real-world insights into physical activity safety and quality of life in pediatric hemophilia A patients on emicizumab.

Findings

Children on emicizumab had a low annualized bleed rate of 0.86 and could safely participate in diverse physical activities.

Most caregivers reported no change or improvement in child activity levels and reduced anxiety about bleeding.

Quality of life scores remained stable over two years of emicizumab use with no new safety concerns.

Abstract

Limited data are available on the relationship between bleeding outcomes and physical activity, and the quality of daily life (QoL), in children with haemophilia A (HA) receiving emicizumab prophylaxis.

TSUBASA evaluated physical activity, bleeding events, safety, and QoL in Japanese people with HA initiating emicizumab prophylaxis. This paper reports the results from the final analysis, focusing on children and adolescents with HA without factor VIII inhibitors, and their caregivers.

TSUBASA was a prospective, multicentre, observational study conducted across 50 medical institutions in Japan. Participants received emicizumab for 97 weeks. Bleeding events and physical activity data were obtained using an electronic patient-reported outcomes application; activity intensity was collected by wearable activity trackers worn over five 8-day monitoring periods. Adverse events (AEs) were documented on the electronic case report form and QoL was assessed using questionnaires.

A total of 46 participants aged <18 years were enrolled; most (84.8%) had severe HA. Over a median observation period of 674 days (quartile 1–quartile 3: 665–690), the mean annualized bleed rate was 0.86 (standard deviation: 1.26). In all Twenty-six participants experienced 66 AEs, of which 2 were injection-site reactions deemed related to emicizumab. J-KIDSCREEN-52 questionnaire scores were maintained from baseline onwards. Of the completed caregiver questionnaires (
n
 = 32), 43.8% reported increased activity and 56.3% reported unchanged activity. Additionally, 56.3% reported decreased anxiety about bleeding and 37.5% reported unchanged anxiety about bleeding. A total of 172 events of physical activity were recorded by 19 participants; 44 were high risk, 70 were moderate risk, and 42 were low risk. One activity-related traumatic bleed resulting from the impact of a basketball occurred, and more than 25 different types of physical activity were performed without bleeding.

Children and adolescents with HA who receive prophylaxis with emicizumab may be able to engage in consistent physical activity, with a low risk of experiencing bleeds. Additionally, the questionnaire responses from caregivers on physical activity and caregiver experience provide rare insights into the real-world impact of emicizumab prophylaxis. These findings present a more comprehensive view of the benefits of emicizumab. No new safety signals were observed and QoL was maintained for 2 years after emicizumab initiation.

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