This is a request for initial feasibility counts to determine the number of patients in CPRD Gold & Aurum that have a diagnosis with Fabry disease. Furthermore, we would like to determine how many of these patients have received enzyme replacement therapy (ERT) since 2001.
Fabry disease is a rare genetic disorder which results in a deficiency of a specific enzyme involved in fat metabolism. The disease affects many parts of the body such as the skin, eyes, heart, kidneys and brain. Fabry disease only affects a very small group of patients which makes it harder for researchers to understand more about the disease and the medicines used to treat it.
Enzyme replacement therapies or ERTs for short are one of the only medicines that treat the underlying cause of Fabry disease. There are only two ERTs available to treat patients and these have been used since 2001 in the United Kingdom.
As part of this study, we would like to explore if Clinical Practice Research Datalink (CPRD) linked with Hospital Episode Statistics (HES) data can be used to assess outcomes of patients diagnosed with Fabry disease who were also treated with an ERT. We also want see if we can determine a cohort of patients who did not receive an ERT and what their long-term outcomes were.
There is a paucity of real-world evidence of the outcomes associated with the use of ERTs in the UK and information generated as part of this study will look to fill some of these evidence gaps.
This is a request for initial feasibility counts to determine the number of patients in CPRD Gold & Aurum that have a diagnosis with Fabry disease. Furthermore, we would like to determine how many of these patients have received enzyme replacement therapy (ERT) since 2001.
Fabry disease (FD) is a rare, X-linked lysosomal storage disorder caused by a mutation in the α-galactosidase A gene on the X-chromosome that results in a deficiency of α-galactosidase A (α-Gal A). Enzyme replacement therapy (ERT) is the main treatment option for FD, with both agalsidase alfa (Replagal®, Takeda) and agalsidase beta (Fabrazyme®, Sanofi Genzyme) being the only approved ERTs for the condition since 2001. Due to the rarity of this disease, there is limited literature available on the real-world effectiveness and safety of ERTs as a treatment option for Fabry disease.
The aim of this study is to generate real-world evidence (RWE) on the outcomes of patients with FD who are treated with ERT and to explore the treatment patterns in FD, in order to support the continued use of Replagal in the UK.
This is a retrospective cohort design, using electronic health care records in CPRD linked to episodic claims data available in HES. Due to the rarity of FD, it is expected that the use of secondary data that includes all general practice patients from a large geographical area of England, will enable as many FD patients to be included as possible.
Outcomes:
- Survival: The proportion of patients who died during the study period. We will also report the amount of available follow-up for these patients.
- HCRU: the number of hospital admissions, outpatient visits and A&E visits for all-causes.
- Immunogenic Outcomes: a combination of laboratory values (IgG increased) and clinical codes suggesting development of antibodies, immunogenic reaction. This will inform the full study and the final list to be defined in association with a KOL and after feasibility analysis.
- Clinical outcomes including renal, cardiovascular and cerebrovascular manifestations
Exposures:
The majority of patients diagnosed with Fabry disease are expected to be treated with one or more of the following disease modifying therapies, with or without supportive therapy for complications of the condition. Treatment will be identified by any prescription of:
- Agalsidase alfa (ATC code A16AB03) in CPRD
- Agalsidase beta (ATC code A16AB04) in CPRD
This feasibility analysis will also aim to determine how many FD patients are not treated with ERTs and are, instead, treated with migalastat, supportive therapies only or are completely untreated. It is expected that this number will be very low.
It is likely to be able to differentiate between agalsidase alfa and agalsidase beta only in a small number of patients. Where possible, objectives will be further assessed among the sub-group of patients who have a record of receiving either agalsidase alfa or agalsidase beta in CPRD. Within this sub-group, objectives will be stratified by ERT type. At least 30 patients in each group are needed for the stratification to be possible.
For most of the objectives, except the descriptive one and treatment patterns, exposure will be treated as a time-dependent variable if indicated from the feasibility analysis that this is necessary.
Linkage to the HES datasets is of particular importance for capturing both HCRU and treatments. HCRU will incorporate the number of patient visits to secondary care as an inpatient, outpatient and through A&E. ERTs are often prescribed in hospital and, therefore, may not be well recorded in CPRD. HES data is needed to ensure all treatment data is captured if this is not wel- recorded within CPRD. HES data will also help us to ensure we capture as many FD patients as possible which is important considering the rarity of the condition. Since ERTs were approved for use in 2001, there has been very little research completed looking at their use in the Fabry population. With the introduction of migalastat, this study could provide up-to-date real-world evidence on the treatment patterns and outcomes of FD patients in England and potentially inform future treatment recommendations and identify any unmet need in this population.
The full study, pending feasibility results, will aim describe and assess overall survival, HCRU, clinical manifestations and outcomes of patients with Fabry disease. Where possible, this will be described in patients who receive ERTs, migalastat, and/or who are untreated. The feasibility study will inform which sub-groupings are appropriate for the size of the study population and confirm the data availability for a variety of outcomes such as death and other clinical outcomes.
Other covariates:
- Demographic variables (e.g. age, sex, BMI)
- Supportive therapies for FD (e.g. ACE inhibitors, beta blockers, pain management)
- Migalastat exposure
- Comorbidities/relevant manifestations of FD (e.g. cardiovascular, renal, gastrointestinal)
- Estimated Glomerular Filtration Rate (eGFR)
- Disease phenotype (e.g. classical or non-classical)
- Others
As Fabry disease is a rare condition, it is likely that some patient groups will be small. In order to protect against potential patient re-identification, all study outputs will suppress any patient numbers where N<5 and any corresponding results that could allow for back-calculation. Further, the feasibility analysis will inform which (if any) sub-groups for analysis will be possible in order to avoid potential re-identification of patients.
Sarah Jenner - Chief Investigator - IQVIA Ltd ( UK )
Zainab Mohamoud - Corresponding Applicant - IQVIA Ltd ( UK )
Clare Flach - Collaborator - IQVIA Ltd ( UK )
HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient