Hereditary angioedema (HAE) is a rare condition which causes recurrent swelling of parts of the body such as the tongue, throat, skin and gastrointestinal tract. Swelling attacks can be disabling and life-threatening. Treatments can be preventative to stop any attacks or given at the time of an actual attack. In the United Kingdom (UK), a particular medication known as androgen is commonly used as treatment but there is very limited scientific evidence available on how widely it is used in the care of HAE patients and what are their side effects (especially long-term), including development of male physical characteristics such as body hair in females), cardiac complications and growths in the liver. The aim of this feasibility study is to assess whether it is possible use the Clinical Practice Research DataLink (CPRD) database linked to the Hospital Episodes Statistics datasets (Inpatient, Outpatient and Accident & Emergency) to describe potential side effects associated with clinical management that included androgen against those that did not. The feasibility studies will determine how to accurately identify HAE patients using CPRD (AURUM and GOLD) and HES and assess completeness of androgen prescriptions and potential side effects. The potential length of follow up following use of androgen, including the duration of use, will be assessed to inform whether long-term side-effects can be described in a future study. The information that this study will provide assist clinicians and patients on choosing the best treatments and how to manage potential side-effects.
Hereditary angioedema (HAE) is a rare condition which causes recurrent swelling of the upper respiratory track, skin and gastrointestinal tract that can be disabling and life-threatening. Treatments can be prophylactic or on demand during angioedema attacks. Androgens have been used in HAE management but the treatment can lead to virilization and cardiac and liver complications. The aim of this feasibility study is to assess whether the Clinical Practice Research DataLink linked to Hospital Episodes Statistics datasets can be used to accurately identify HAE patients, including determining appropriateness of using ICD 10 code 84.1 for Defects in the complement system [C1 esterase inhibitor deficiency] in combination with care specialty code (for allergist/immunologist). It will also assess the completeness of androgens use (danazol and stanozolol) and other treatments (e.g. c1-esterase inhibitor both plasma derived and recombinant, tranexamic acid) as well as potential length of follow-up post androgen therapy for estimating long-term outcomes and adverse effects (from HES inpatient, outpatient, Accident & Emergency datasets, and Death Registry). This information will be used to plan a future retrospective cohort study to describe and compare the rate of adverse events and health resource utilisation for patient who received androgen therapy compared to those who did not. Adverse events of interest will include myocardial infarction, diabetes, renal disease, liver cancer, psychological disorders, thyroid disorders. Basic summary statistics (including counts, proportions, mean and, standard deviations, medians and interquartile ranges, etc) will be obtained. Rates in person-time will be calculated wherever appropriate. Mitigation measures will be applied during analysis to suppress any finding on less than five patients to prevent any likelihood of their identification. The findings of this study on the beneficial and adverse effects of androgen will be disseminated in the public domain to assist clinicians and patients on their choice of best treatment strategies.
Age; sex; smoking history; alcohol consumption; Hypertensive diseases; ischaemic heart diseases; other forms of heart disease; cerebral infarction; acne; obesity; diabetes mellitus; hypercholesterolaemia; hyperlipidaemia; mental and behavioural disorders; benign neoplasm of the liver; other diseases of liver; disorders of thyroid gland
Mortality (cause-specific, overall; number, and proportions)
Survival (feasibility of defining and estimating disease-free or progression-free, overall)
Hospitalisation, outpatient visits and general practice consultation (cause-specific and overall)
Indraraj Umesh Doobaree - Chief Investigator - Takeda UK Limited
Indraraj Umesh Doobaree - Corresponding Applicant - Takeda UK Limited
Ananya Roy Chowdhury - Collaborator - Takeda Development Center Americas, Inc.
Ning (Julia) Zhu - Collaborator - Takeda Development Center Americas, Inc.
SUDHAKAR MANNE - Collaborator - Takeda Development Center Americas, Inc.
CPRD Aurum Pregnancy Register;CPRD GOLD Pregnancy Register;CPRD GOLD Mother-Baby Link;HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;CPRD Aurum Mother-Baby Link;Practice Level Index of Multiple Deprivation (Standard)