Epidemiology, Natural History and Burden of Disease in Patients with Alpha-1 Antitrypsin Deficiency in the UK: A Real-World Retrospective Cohort Study

Date of Approval: 
2020-12-01 00:00:00
Lay Summary: 
Alpha-1 antitrypsin deficiency (AATD) is a rare condition involving the lack of a protein made by the liver. Individuals with AATD experience lung or liver disease. The condition is commonly identified in adults with lung disease, but has also been diagnosed in adults and children with liver disease. Patients may experience long delays before being diagnosed with AATD because early symptoms are similar to other common respiratory conditions, including asthma and chronic obstructive pulmonary disease (COPD). In the UK, studies suggest that new cases of AATD have increased between 1994 and 2013. However, there is limited data on disease burden in patients with AATD in the UK. The aim of this study is to determine how many people live with AATD in the UK, how many are diagnosed each year, and what frequency of other diseases may co-exist with AATD. We also plan to describe treatment patterns, referrals from general practitioners (GPs), and death rates based on patients seen in primary care. In addition, the study will describe health care use among AATD patients. Comparisons will be made with patients diagnosed with COPD. The public health benefit and importance of this study is highlighted by the lack of information regarding the burden of disease among patients with AATD in the UK. The study will offer a better understanding of the patient journey and how it has evolved over time.
Technical Summary: 
AATD is a rare inherited disorder and may cause serious lung disease, (i.e. emphysema or COPD), liver disease, or skin rashes. Limited data exists regarding disease burden in AATD patients. This study aims to evaluate the epidemiology, comorbidities, treatment patterns, testing and referrals, mortality and health care utilisation associated with AATD in the UK between 1990 and 2020. AATD patients will be selected using validated Read codes indicative of an AATD diagnosis or an ICD-10 diagnosis code in HES. A non-AATD COPD-control cohort will be selected for comparisons using 1:1 exact matching based on age at index, sex, general practice, and index year. Statistical analysis will be primarily descriptive, consisting of mean, median and standard deviation for continuous variables, and frequency counts and percentages for categorical variables. For comparative analyses, differences between AATD patients and COPD controls will be evaluated using a Wilcoxon signed rank test for continuous variables and McNemar’s tests for categorical variables. Treatment patterns will be described as frequencies in the first, second and third years following diagnosis. Health care utilisation will be evaluated as the proportion of patients with each type of resource use in primary and secondary care and utilisation rates per person year. Mortality rates will be estimated in a time-to-event framework using Kaplan-Meier survival analysis and comparisons between AATD and COPD cohorts will be made using a log-rank test. Hazard ratios will be estimated using a Cox proportional hazards model and the proportional hazards assumption will be tested. Epidemiological results will be stratified by age-group (e.g. <12 years, 13-17 years, <18 years, 18+ years), sex and time period (e.g. 1990-1999, 2000-2009, 2010-2019). The study will generate new evidence regarding the epidemiology and natural history of AATD, based on primary care data representative of the UK population.
Health Outcomes to be Measured: 
Study outcomes will include prevalence counts and incidence rates for AATD, demographics and background characteristics (e.g. age at index date, sex, smoking status, alcohol status), prevalence of comorbidities (e.g. COPD, bronchiectasis, asthma, emphysema, cirrhosis, jaundice, coronary heart disease, stroke, hypertensive diseases, diabetes mellitus, heart failure, depressive disorder, osteoporosis), tests and referrals from primary care. Additional study outcomes will include frequencies of different treatments (e.g. bronchodilators, mucolytics, corticosteroids, pulmonary rehabilitation, smoking cessation therapy) for AATD, and mortality rates. Through linking CPRD with HES Admitted Patient Care (APC), Outpatient (OP) and Accident & Emergency (A&E) data, frequency of lung/liver transplants, lung volume reduction surgery and health care utilisation will be measured.
Application Number: 

Zheng-Yi Zhou - Chief Investigator - Analysis Group, Inc.
Nisha Hazra - Corresponding Applicant - Analysis Group Ltd
Cassie Tang - Collaborator - Analysis Group, Inc.
Riley Taiji - Collaborator - Analysis Group, Inc.

HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation