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Inflammatory Bowel Disease Patients Are at Increased Risk of Invasive Pneumococcal Disease: A Nationwide Danish Cohort Study 1977–2013

Kantsø, Bjørn MSc1; Simonsen, Jacob MSc, PhD2; Hoffmann, Steen MD3; Valentiner-Branth, Palle MD, PhD4; Petersen, Andreas Munk MD, PhD5,6; Jess, Tine MD, DMSc2,7

American Journal of Gastroenterology: November 2015 - Volume 110 - Issue 11 - p 1582–1587
doi: 10.1038/ajg.2015.284

OBJECTIVES: Inflammatory bowel disease (IBD), Crohn’s disease (CD), and ulcerative colitis (UC) are chronic diseases characterized by an inappropriate immune response, which may also increase the risk of infections. We investigated the risk of invasive pneumococcal disease (IPD) before and after diagnosis of IBD in a population-based cohort study.

METHODS: In a cohort of 74,156 IBD patients and 1,482,363 non-IBD controls included and followed during 1977–2013, hazard rate ratios (HRs) for IPD in IBD patients vs. controls were calculated by Cox regression. Within the IBD group, we also calculated the risk according to ever use of specific IBD medications. Next, using conditional logistic regression, we evaluated the odds of IPDpriorto IBD diagnosis.

RESULTS: The HRs for IPD within the first 6 months after IBD diagnosis were significantly and more than threefold increased and then decreased to a constant level, which for CD was significantly increased (approximately twofold, HR, 1.99; 95% confidence interval (CI), 1.59–2.49) and for UC non-significantly just above 1. IBD medication use including tumor necrosis factor alpha antagonists had limited impact on the risk of IPD, although having ever used azathioprine increased the risk of IPD in patients with UC (HR, 2.38; 95% CI, 1.00–5.67). Up to 4 years prior to IBD diagnosis, the odds ratio for IPD was significantly increased (UC HR, 1.51, 95% CI, 1.05–2.17; CD HR, 1.79, 95% CI, 1.05–3.03).

CONCLUSIONS: The risk of IPD is significantly increased both before and after diagnosis of IBD, with limited impact of IBD medications. This suggests that the risk of IPD in patients with IBD is related to the underlying altered immune response in these patients.

1Department of Microbiological Diagnostics and Virology, Statens Serum Institut, Copenhagen, Denmark

2Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark

3Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark

4Department of Infectious Disease Epidemiology, Statens Serum Institut, Copenhagen, Denmark

5Department of Gastroenterology, Hvidovre University Hospital, Hvidovre, Denmark

6Department of Clinical Microbiology, Hvidovre University Hospital, Hvidovre, Denmark

7Department of Clinical Epidemiology, University of Aalborg, Aalborg, Denmark

Correspondence: Bjørn Kantsø, MSc, Department of Microbiological Diagnostics and Virology, Statens Serum Institut, Artillerivej 5, Copenhagen DK-2300, Denmark. E-mail:

SUPPLEMENTARY MATERIAL accompanies this paper at

Received 26 February 2015; accepted 28 July 2015

Guarantor of the article: Bjørn Kantsø, MSc.

Specific author contributions: B.K. initiated the study. J.S. performed statistical analyses, designed the study, and collected data. S.H. provided data on IPD. All authors were involved in planning the study and in the interpretation of findings. B.K. drafted the manuscript, which was critically revised by all co-authors. All authors contributed to the final manuscript.

Financial support: The A.P. Møller Foundation for the Advancement of Medical Science kindly supported this study.

Potential competing interests: None.

© The American College of Gastroenterology 2015. All Rights Reserved.
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