Clinical trial NCT03835780: The Risk of Venous Thromboembolism in Systemic Inflammatory Disorders: a United Kingdom (UK) Matched Cohort Study
Official title: The Risk of Venous Thromboembolism in Systemic Inflammatory Disorders: a UK Matched Cohort Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Venous Thromboses
Venous Thromboembolism
Deep Vein Thrombosis
Pulmonary Embolism
Rheumatoid Arthritis
Inflammatory Bowel Diseases
Ulcerative Colitis
Crohn Disease
Psoriatic Arthritis
Lead sponsor: Momentum Data
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
name: University of Surrey
First posted: 2019-02-11
Enrollment: 266890
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The exposed cohort includes all individuals with an existing or incident diagnosis of IBD, RA or PsA (systemic inflammatory diseases) in the RCGP RSC over the study period. IBD, RA or PsA will be identified using Read diagnostic codes previously validated in UK primary care studies.

The matched unexposed cohort will be defined by matching individuals in the exposed cohort with individuals never diagnosed with a systemic inflammatory disease either prior to or during the study period by age and sex. Unexposed individuals require at least 1 year of follow-up when matched to minimize the risk they had a non-recorded existing diagnosis of a systemic inflammatory disease of interest. Follow-up for each matched individual will begin at the start of follow-up of their matched counterpart.

Brief summary: Blood clots occurring in the legs and in the lungs are relatively common; they occur in around 3 in a 1000 people per year. They can cause disability and are also potentially life threatening. When a clot occurs in the legs it is called a deep vein thrombosis or DVT. When they occur in the lungs they are called a pulmonary embolism or PE. The risk for DVT and PE is higher in people with conditions which cause inflammation. The most common of these are inflammatory bowel disease (ulcerative colitis and Crohn's disease), rheumatoid arthritis, and psoriatic arthritis (a condition comprised of psoriasis and joint inflammation).

What is not known is how much higher the risk of DVT and PE is in these groups compared with people without inflammatory disease, and what causes the excess risk in these people. This study aims to assess the measure the exact increase in risk for DVT and PE in people with these inflammatory conditions and to identify which risk factors are most strongly associated with the increased risk. These data should help with an understand the causes of blood clot risk in these inflammatory conditions and in identify targets for reducing risk.

Detailed description: Background

Venous thromboembolism (VTE), comprising pulmonary embolism (PE) and deep vein thrombosis (DVT), are common and associated with significant morbidity and mortality. VTE risk is higher in chronic inflammatory conditions including inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) compared to the general population. Evidence for differential VTE risk in other inflammatory diseases, notably psoriatic arthritis (PsA) and vasculitis, is more limited. Risk factors for VTE have been described in the general population, but there has been little interrogation of VTE risk factors for individuals with chronic inflammatory conditions and their association with subsequent VTE.

Objective

This study aims to describe the prevalence of VTE risk and risk factors in individuals with systemic inflammatory disorders in a contemporary real-world population, by disease type (IBD, RA, and PsA) and relative to a control population without systemic inflammatory disease. In the same cohorts a further comparison will be performed of the influence of VTE risk factors on risk of VTE events in individuals with systemic inflammatory disorders.

Method

A retrospective cohort study will be performed to compare VTE risk and VTE risk factors in adults with IBD, RA, and PsA and matched controls between January 1, 1998 and January 1, 2018, within the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) network. In the cohorts with and without inflammatory conditions estimate will be determined for the risk of VTE overall, and for PE and DVT separately, using unadjusted Cox proportional hazards models, stratified by matched set (exposed cohort versus unexposed cohort), to provide overall hazard ratios for the association with each outcome. Models will be subsequently adjusted for sociodemographic and clinical and VTE risk factors in multivariable analysis to explore potentially important associations with VTE. The same analyses for each autoimmune condition will be repeated separately. Prespecified sensitivity analyses will be performed to explore the robustness of any potential associations.

Eligibility criteria: Inclusion Criteria:

* Adult patients (aged ≥18) contributing to RCGP RCS primary care database between January 1, 1998 and January 1, 2018, will be eligible for inclusion

Exclusion Criteria:

* People with IBD which cannot be classified or is not ulcerative colitis or Crohn's disease will be excluded.

Primary outcomes:
measure: Risk of Venous Thromboembolism (VTE)
timeFrame: A 20 year analysis period (1999-2018 inclusive)
Secondary outcomes:
measure: Risk of Pulmonary Embolism (PE)
timeFrame: A 20 year analysis period (1999-2018 inclusive)
measure: Risk of Deep Vein Thrombosis (DVT)
timeFrame: A 20 year analysis period (1999-2018 inclusive)
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Momentum Data Ltd
Study officials:
affiliation: Momentum Data
name: Andrew McGovern, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Irving PM, de Lusignan S, Tang D, Nijher M, Barrett K. Risk of common infections in people with inflammatory bowel disease in primary care: a population-based cohort study. BMJ Open Gastroenterol. 2021 Feb;8(1):e000573. doi: 10.1136/bmjgast-2020-000573.
citation: Galloway J, Barrett K, Irving P, Khavandi K, Nijher M, Nicholson R, de Lusignan S, Buch MH. Risk of venous thromboembolism in immune-mediated inflammatory diseases: a UK matched cohort study. RMD Open. 2020 Sep;6(3):e001392. doi: 10.1136/rmdopen-2020-001392.