Inflammatory bowel disease (IBD) is an umbrella term used to describe disorders that involve chronic inflammation of digestive tract. IBD consists of two major disorders, ulcerative colitis (UC) and Crohns disease (CD). Both UC and CD are chronic diseases that generally begin in young adulthood and last throughout life. The incidence of IBD, which is a measure of the probability of occurrence of IBD within a time-period, is increasing worldwide, and the diseases remain incurable. IBD patients are high-risk populations for opportunistic infections - a condition caused by pathogens (bacteria, viruses, fungi, or protozoa) that take advantage of an opportunity not normally available, such as a host with a weakened immune system.
In this study, we aim to determine the incidence rates of opportunistic infections in patients diagnosed with IBD. We will also determine whether the incidence of opportunistic infections differs by age, gender, year of IBD diagnosis, and comorbidity status (HIV, malignancy, CVD, depression, hypertension, diabetes, fractures/osteoporosis and autoimmune diseases).
This is a hypothesis generating retrospective cohort study to estimate the incidence rates of opportunistic infections in patients diagnosed with IBD, stratified by type of opportunistic infections, age group, gender, year of cohort entry and pre-existing of comorbid conditions. UC or CD or indeterminate IBD patients with at least one year of history/registration in CPRD will be included and followed from their initial diagnosis of UC or CD or indeterminate IBD to censor in the data, the censor date is the earliest of the following: 1) The occurrence of an opportunistic infection (separately for each event), 2) Loss of eligibility, 3) Death, 4) End of data collection. We will use Byars method or exact method to estimate IR and IRR between strata with 95% confidence intervals (CIs) for each type of opportunistic infection. We will provide cumulative incidence functions of the first infection for each study outcome at various time of follow-up using the Kaplan Meier method. Proportions will be compared using a chi-square test or, where cell sizes are less than 5, a Fishers exact test. Kaplan Meier curves will be compared using a log rank test. Statistical analyses will be carried out using SAS Release 9.4 (SAS Institute Inc., Cary NC, USA).
Study outcome events will be opportunistic infections occurring during the follow-up period. Opportunistic infections will be categorized as the following types:
Viral: CMV, EBV, HSV, varicella zoster, HBV, HCV
Fungal: histoplasmosis, candidiasis, and blastomycosis
Bacterial: tuberculosis and streptococcal
We will define a new infection as a diagnosis code for infection when no prior infection code of the same type is observed within at least the previous 6 months. Tuberculosis, HBV, and HCV are chronic infections; thus, patients with a prior diagnosis of HBV, HCV, and Tuberculosis at any time prior to a diagnosis of IBD will be excluded from these analyses. Only the first diagnosis of these infections after the diagnosis of IBD will be counted. The incidence rate of each specific opportunistic infection will be estimated and stratified by age category, gender, year of cohort entry and different comorbidity status (HIV, malignancy, CVD, depression, hypertension, diabetes, fractures/osteoporosis and autoimmune diseases).
Sally Lee - Chief Investigator - Celgene Ltd
Sally Lee - Corresponding Applicant - Celgene Ltd
Ran Gao - Collaborator - Boehringer-Ingelheim International GmbH
Steve Niemcryk - Collaborator - Celgene Ltd
Tongsheng Wang - Collaborator - Celgene Ltd