This study focuses on autoimmune disorders, which are very serious conditions affecting over 1 million patients in the UK. Among others, they include diseases like multiple sclerosis and rheumatoid arthritis. Over time, these conditions often result in heart diseases, strokes or blood clots. This study seeks both to assess how often these complications occur, and to determine the impact of specific pharmaceutical treatments on the frequency of such complications. Understanding how certain medications can trigger cardiovascular conditions in patients with autoimmune disorders will help reduce, and in some cases even prevent, the development of such life-threatening side effects. We estimate that it could benefit thousands of patients in the UK and throughout the world.
More specifically, this study will focus on the following autoimmune disorders: Addison's disease, ankylosing spondylitis, coeliac disease, type 1 diabetes, inflammatory bowel diseases, myasthenia gravis, multiple sclerosis, pernicious anemia, polymyalgia rheumatica psoriasis, primary biliary cirrhosis, rheumatoid arthritis, Sjögren's syndrome, systemic sclerosis, systemic lupus erythematosus, thyroid diseases, vasculitis, and vitiligo.
A recent CPRD study of Conrad et al. (2022) showed an elevation of the incidence of a dozen cardiovascular (CV) events in 19 autoimmune diseases (AIDs) and showed a decline in the relative risk associated to AIDs from 1.6 in 2000-2004 to 1.24 in 2015-2019 [1]. The contribution of different AIDs-targeted medications on this CV risk and its decline is still unknown and under investigated. The objective of this study is to assess whether the recommended lower use of non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids (CS) in AID patients occurred and translated into a decline of CV risk in the UK in 2000-2022. We will also evaluate the contribution of the following groups of AIDs targeted drugs to the CV risk and its decline: synthetic antimalarial drugs, methotrexate, classical immunosuppressants, and biotherapies. For that purpose, a cohort of incident patients with the 19 main AIDs will be followed from 2000 to 2022 in CPRD Aurum and GOLD linked to HES datasets.
The relative risk of CV events according to the amount of CS and NSAIDs use over time will be assessed in a logistic regression controlling for age, sex, comorbidities, and socioeconomic status, also controlling for other treatments and risk factors use. To study the CV risk linked to the use of different type of AID treatment, new drug users of hydroxychloroquine, methotrexate, classical immunosuppressive drugs (all) and biotherapies (all) will be matched to patients from the AIDs cohort without the use of these drugs at the same period. Matching will be done on individual disease, sex, age, high dimensional propensity scores, and stage of the disease. A Cox proportional hazards model adjusted for socioeconomic status and time-varying non CV comorbidities will assess the hazard rate of CV events for each group of AIDs-targeted drug users as compared to non-users.
Primary outcome
Any of the following CV events leading to hospitalization or emergency management:
A. Inflammatory CV events: pericarditis (of non-infectious origin), myocarditis, and endocarditis.
B. Thromboembolic events: myocardial infarction, acute coronary syndrome, stroke (ischemic and hemorrhagic) or transient ischemic attack (TIA), and venous thromboembolism or pulmonary embolism.
C. Arrhythmias: atrial fibrillation and flutter, and supraventricular arrhythmias or conduction system disease.
D. Other CV disorders: aortic aneurysm, peripheral arterial disease, valve disorders (excluding congenital and rheumatic), and heart failure.
Key secondary outcomes
- Immunologic CV events, thromboembolic events, arrhythmias or other cardiac diseases (A, B, C or D CV events above) will be studied separately;
- Use of CS will be studied as an outcome in a secondary analysis.
billy amzal - Chief Investigator - RE-MED France SAS
Tom Duchemin - Corresponding Applicant - RE-MED France SAS
Yann Hamon - Collaborator - RE-MED France SAS
Yola Moride - Collaborator - RE-MED France SAS
billy amzal - Collaborator - RE-MED France SAS
Médéa Locquet - Collaborator - RE-MED France SAS
HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data