The use of a National Database and patient reporting tool (Haemtrack) to determine the "real-world" outcomes of UK patients with haemophilia A treated using factor VIII replacement

Abstract

Congenital haemophilia A (HA) is an x-linked recessive disorder associated with a deficiency of clotting factor VIII (FVIII), which manifests as a propensity to bleed. Individuals with severe HA (SHA) and moderate HA (MHA) of severe phenotype, bleed spontaneously, typically into joints and muscle and develop significant musculoskeletal morbidity if not treated adequately. The standard of care for this group of patients is to use prophylactic FVIII therapy to prevent bleeding, but there is considerable variability in treatment patterns. Few large-scale, high-quality studies exist to describe this practice and the associated outcomes accurately. Haemtrack (HT) is an electronic diary, that is used by UK patients with HA to record bleeding events and treatment. The research potential of HT has not been widely explored. This investigation describes the validation and application of HT as a tool to investigate current treatment practices and outcomes for HA in the UK. Haemtrack was used by 90% of haemophilia Treatment Centres (HTCs) in 2015; registrants included 68% of all UK patients with SHA. Age distribution and treatment intensity were similar in HT users/non-users for patients with SHA treated prophylactically. Prophylaxis was used in 94.9% of HT-compliant children 40 years. Median ABR increased with age (1.0, 40 years). Prophylaxis was used by 68.8% of HT-compliant MHA patients, associated with a median ABR of 3.0. Median haemophilia joint health score increased with age in SHA and MHA. 80.4% of patients with SHA and 60.1% with MHA reported prophylaxis > 3 times/week. Only a minority of patients treated prophylactically were bleed free (40% SHA, 19% MHA). Between 2016 and 2019, 210 patients switched treatment to extended half-life FVIII, rFVIIIFc. This was associated with a significant reduction in treatment intensity and bleeding; the proportion of bleed-free patients increasing from 36% to 53%. The data collated by HT is representative of the UK SHA and severe phenotype MHA population, using prophylactic FVIII treatment. Prophylaxis is used by a high proportion of patients, but there is inter-personal variability in practice and outcome. Patients with MHA of severe phenotype are treated less intensively and have comparable outcomes to those with SHA. In selected patients, EHL-FVIII can be used to improve bleeding outcomes, whilst reducing treatment burden.

Date of Award	1 Aug 2021
Original language	English
Awarding Institution	The University of Manchester
Supervisor	John Burthem (Supervisor) & Charles Hay (Supervisor)