Rare diseases are individually rare but collectively common with 1 in 17 individuals affected during their lifetime. Patients with rare diseases frequently describe a long path to diagnosis. Antinuclear antibody (ANA)- associated diseases are a group of rare diseases that affect different parts of the body. Diagnosing these patients is difficult, the ANA blood test used to help diagnose these patients, does not always give a clear answer. It may be positive in those who do not appear to have disease (at least at the time of testing). We suspect that these ANA-positive patients may have higher rates of other problems compared to the general population, and there may be features that can help to distinguish those who will later develop disease.
We aim to describe what happens to patients with an ANA-positive test in primary care and identify features that may predict who will develop disease.
We will start by reviewing what is known about the problems ANA-positive patients suffer.
Then, using the findings of step 1, we will use CPRD a research database of GP records to look at patients who have had an ANA test comparing those with a positive test to those without. We hope that we will find risk factors that help predict which of these patients will later develop disease. These risk factors could be used to alert doctors to those patients at greater risk of developing active disease, shortening the time to diagnosis, and ultimately improving patients’ lives.
Objective
To investigate the natural history and subsequent diagnoses of patients who have had an Antinuclear antibody (ANA) test performed and identify features that suggest those who may later develop ANA-associated diseases.
Outcome
A composite outcome of ANA-associated diseases (autoimmune connective tissue disease, systemic lupus erythematosus (SLE), myositis, Sjogren’s syndrome, scleroderma, mixed connective tissue disease, autoimmune hepatitis, interstitial pneumonia with autoimmune features (IPAF) and autoimmune thyroid disease).
Methods
CPRD Aurum will be used to conduct a cohort study of patients who have had an ANA test performed (the exposure), with each case matched to a single control. A further cohort study will be performed matching each ANA positive case with up to 10 controls, for this analysis cases and controls this second cohort will be linked to secondary care and mortality data to enhance outcome capture.
Analysis
Descriptive statistics of the exposure and control groups, including the prevalence of patients who have had an ANA test. Poisson regression will be performed to identify baseline factors associated with testing.
The incidence of proposed factors associated with subsequent ANA-associated diseases, will be compared, between ANA positive patients and controls. Cox-proportional hazard models will be performed from the time of testing (or equivalent for controls) to assess the impact of proposed predictors for developing ANA-associated disease.
A composite analysis of the first diagnosis of ANA associated diseases: AI-CTD (Autoimmune connective diseases); systemic lupus erythematosus (SLE); myositis, Sjogren’s syndrome, scleroderma, mixed connective tissue disease, autoimmune hepatitis, interstitial pneumonia with autoimmune features (IPAF) and autoimmune thyroid disease.
All cause and cardiovascular mortality will also be captured.
CPRD Aurum and HES APC will be used to identify the composite outcome.
ONS will be used to identify mortality.
William Evans - Chief Investigator - University of Nottingham
William Evans - Corresponding Applicant - University of Nottingham
Fiona Pearce - Collaborator - University of Nottingham
Nadeem Qureshi - Collaborator - University of Nottingham
Peter Lanyon - Collaborator - Nottingham University Hospitals
Yana Vinogradova - Collaborator - University of Nottingham
HES Admitted Patient Care;ONS Death Registration Data;Practice Level Index of Multiple Deprivation