Risk of common infections in people with inflammatory bowel disease in primary care: a population-based cohort study

Abstract

Objective: To evaluate the risk of common infections in individuals with inflammatory bowel disease (IBD) [ulcerative colitis and Crohn's disease] compared with matched controls in a contemporary UK primary care population.

Design: Matched cohort analysis (2014-2019) using the Royal College of General Practitioners Research and Surveillance Centre primary care database. Risk of common infections, viral infections and gastrointestinal infections (including a subset of culture-confirmed infections), and predictors of common infections, were evaluated using multivariable Cox proportional hazards models.

Results: 18 829 people with IBD were matched to 73 316 controls. People with IBD were more likely to present to primary care with a common infection over the study period (46% vs 37% of controls). Risks of common infections, viral infections and gastrointestinal infections (including stool culture-confirmed infections) were increased for people with ulcerative colitis and Crohn's disease compared with matched controls (HR range 1.12-1.83, all p<0.001). Treatment with oral glucocorticoid therapy, immunotherapies and biologic therapy, but not with aminosalicylates, was associated with increased infection risk in people with IBD. Despite mild lymphopenia and neutropenia being more common in people with IBD (18.4% and 1.9%, respectively) than in controls (6.5% and 1.5%, respectively), these factors were not associated with significantly increased infection risk in people with IBD.

Conclusion: People with IBD are more likely to present with a wide range of common infections. Health professionals and people with IBD should remain vigilant for infections, particularly when using systemic corticosteroids, immunotherapies or biologic agents.

Trial registration number: Clinicaltrials.gov (NCT03835780).

Keywords: Crohn's disease; inflammatory bowel disease; primary care; ulcerative colitis.

Conflict of interest statement

Competing interests: KB has received honoraria from Tillots, Thermo Fisher Scientific, Boehringer Ingelheim, Pfizer, and Yakult. SdeL is director of the RCGP RSC, he has received funding through his universities from Eli Lilly, GSK, Astra Zeneca, MSD, Sanofi, Seqirus, and Takeda. DT and MN are employees of Pfizer. PMI has received lecture fees from AbbVie, Celgene, Falk Pharma, Ferring, MSD, Janssen, Pfizer, Takeda, Tillotts, Sapphire Medical, Sandoz, Shire, and Warner Chilcott; financial support for research from MSD, Pfizer, and Takeda; advisory fees from AbbVie, Arena, Genentech, Gilead, Hospira, Janssen, Lilly, MSD, Pfizer, Pharmacosmos, Prometheus, Roche, Sandoz, Samsung Bioepis, Takeda, Topivert, VH2, Vifor Pharma, and Warner Chilcott.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Adjusted HRs for associations between ulcerative colitis and Crohn’s disease and (A) primary infection outcomes; (B) ssub-infection outcomes. A HR greater than 1 represents an increase in the risk in individuals with IBD compared with matched controls without IBD. Models adjusted for age, sex, IMD quintile, white ethnicity, BMI category, smoking status, alcohol category, hypertension, hyperlipidaemia, type 2 diabetes, peripheral arterial disease, atrial fibrillation, angina, myocardial infarction, stroke, heart failure, chronic kidney disease stage 3–5, chronic obstructive pulmonary disorder, chronic liver disease, malignancy, dementia, rheumatoid arthritis, fracture history, depression and medication use (rectal 5-ASA, rectal glucocorticoids, oral 5-ASA, oral glucocorticoids, immunotherapies and biologic therapies). *Composite of organism specific infection with Clostridium difficile, Salmonella, Shigella or Campylobacter infections. ASA, aminosalicylic acid; BMI, body mass index; GI, gastrointestinal;IBD, inflammatory bowel disease; IMD, index of multiple deprivation; UTI, urinarytract infection.

Figure 2

Adjusted hazard ratios for associations between baseline medication use and subsequent risk of presentation of common infection in individuals with ulcerative colitis and Crohn’s disease. A HR greater than 1 represents an increase in the risk of presentation of infection in individuals using the medication of interest compared with individuals not using that medication. Models adjusted for age, sex, IMD quintile, white ethnicity, BMI category, smoking status, alcohol category, hypertension, hyperlipidaemia, type 2 diabetes, peripheral arterial disease, atrial fibrillation, angina, myocardial infarction, stroke, heart failure, chronic kidney disease stage 3–5, chronic obstructive pulmonary disorder, chronic liver disease, malignancy, dementia, rheumatoid arthritis, fracture history, depression and concomitant medication use (from rectal 5-ASA, rectal glucocorticoids, oral 5-ASA, oral glucocorticoids, immunotherapies and biologic therapies). ASA, aminosalicylic acid; BMI, body mass index; GI, gastrointestinal; IBD, inflammatory bowel disease; IMD, index of multiple deprivation.

Figure 3

Association of continuous time-varying lymphocyte and neutrophil count with risk of presentation of common infection in individuals with and without inflammatory bowel disease. Lymphocyte and neutrophil counts each modelled a restricted cubic spline with three knots in a multivariable model*. Associations are shown relative to the mean count in individuals with IBD (lymphocyte count 1.7×109 cells/L; neutrophil count 4.4×109 cells/L), up to the 99.5th centile of each count variable. Grey shading represents 95% CIs. *Models adjusted for age, sex, IMD quintile, white ethnicity, BMI category, smoking status, alcohol category, hypertension, hyperlipidaemia, type 2 diabetes, peripheral arterial disease, atrial fibrillation, angina, myocardial infarction, stroke, heart failure, chronic kidney disease stage 3–5, chronic obstructive pulmonary disorder, chronic liver disease, malignancy, dementia, rheumatoid arthritis, fracture history, depression and medication use (rectal 5-ASA, rectal glucocorticoids, oral 5-ASA, oral glucocorticoids, immunotherapies and biologic therapies. With IBD (n=15 290, infection events=6692), (A) lymphocyte count and (B) neutrophil count. Controls (n=44 324, infection events=16 332), (C) lymphocyte count and (D) neutrophil count. ASA, aminosalicylic acid; BMI, body mass index; IBD, inflammatory bowel disease; IMD, index of multiple deprivation.