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HISTOLOGICAL ACTIVITY IN INFLAMMATORY BOWEL DISEASE AND RISK OF SERIOUS INFECTIONS: A NATIONWIDE STUDY

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Introduction

Individuals with inflammatory bowel disease (IBD) are at increased risk of serious infections, but it is unclear if this risk varies by histological disease activity.

Aims & Methods

A nationwide study of 55,626 individuals diagnosed with IBD in 1990-2016 with longitudinal data on ileo-colorectal biopsies followed through 2016. Serious infections were defined as having an inpatient infectious disease diagnosis in the Swedish National Patient Register. We used Cox regression to estimate hazard ratios (HRs) for serious infections, sepsis and opportunistic infections during periods of histological inflammation (vs. periods of histological remission) adjusting for socio-demographics, comorbidities, prior IBD-related surgery, hospitalization, and in sensitivity analyses also for IBD-related medications.

Results

During periods with histological inflammation vs remission, there were 4.62 (95%CI=4.46-4.78) and 2.53 (95%CI=2.36-2.70) serious infections per 100 person-years of follow-up, respectively (adjusted [a]HR=1.59; 95%CI=1.48-1.72), or one extra serious infection per 50 IBD patients with histologic inflammation followed for 12 months. Periods of histological inflammation (vs remission) were associated with an increased risk of serious infections in both ulcerative colitis (UC, aHR=1.68; 95%CI=1.51-1.87) and Crohn’s disease (CD, aHR=1.59; 95%CI=1.40-1.80). The aHR of sepsis and opportunistic infections were 1.66 (95%CI=1.28-2.15) and 1.71 (95%CI=1.22-2.41), respectively. Results were consistent across age groups (Table 1), and remained robust after adjustment for IBD-related medications (aHR=1.47; 95%CI=1.34-1.61). Finally, among individuals with clinically quiescent IBD, defined as no prior IBD-related surgery, hospitalization or treatment escalation, histological inflammation (versus histological remission) was associated with an increased risk of serious infections (aHR=1.33; 95%CI=1.13-1.57).

Table 1 Risk of serious infection during periods of histological inflammation and histological remission of inflammatory bowel disease (IBD)

	N (% of total)		N infections (%)		Follow-up years		IR (95% CI) by 100 PY		HR (95% CI)
	Histological inflammation	Histological remission	Histological inflammation	Histological remission	Histological inflammation	Histological remission	Histological inflammation	Histological remission	HR (95% CI)
Overall	68 666 (100%)	34 680 (100%)	3 271 (4.8%)	853 (2.5%)	70 846	33 666	4.62 (4.46-4.78)	2.53 (2.36-2.70)	1.59 (1.48-1.72)
Age at index date
<18y	4 795 (7.0%)	1 871 (5.4%)	247 (5.2%)	60 (3.2%)	5 052	1 817	4.89 (4.28-5.50)	3.30 (2.47-4.14)	1.44 (1.08-1.92)
18 - <40y	26 282 (38.3%)	11 730 (33.8%)	1 115 (4.2%)	289 (2.5%)	27 319	11 376	4.08 (3.84-4.32)	2.54 (2.25-2.83)	1.47 (1.28-1.68)
40 - <50y	23 306 (33.9%)	13 448 (38.8%)	833 (3.6%)	231 (1.7%)	24 220	13 107	3.44 (3.21-3.67)	1.76 (1.54-1.99)	1.66 (1.43-1.93)
50 - <60y	14 283 (20.8%)	7 631 (22.0%)	1 076 (7.5%)	273 (3.6%)	14 254	7 364	7.55 (7.10-8.00)	3.71 (3.27-4.15)	1.51 (1.32-1.74)
≥60y	4 795 (7.0%)	1 871 (5.4%)	247 (5.2%)	60 (3.2%)	5 052	1 817	4.89 (4.28-5.50)	3.30 (2.47-4.14)	1.44 (1.08-1.92)

Hazard ratios (HR) adjusted for age at index date (i.e., start of exposure period), sex, calendar year, education level, country of birth, disease duration, any history of inpatient IBD care, IBD-related surgery, and comorbidity (diabetes, hypertension, chronic autoimmune disease and asthma).CD, Crohn’s disease; IR, Incidence rate; UC, Ulcerative colitis

Conclusion

Histological inflammation of IBD was an independent risk factor for serious infections, including sepsis, suggesting that achieving histological remission may reduce infections in IBD