Introduction
Immunomodulators and biologicals play an essential role in current IBD management, but are associated with increased risk of infections. In light of the growing number of treatment options, the benefit-risk balance of drugs is becoming increasingly important in clinical decision making. Post-marketing surveillance studies are pivotal to assess infection risk, yet mainly focus on severe infections. As a result, data on mild and moderate infections are scarce. However, mild and moderate infections take longer to clear in immunosuppressed patients, have been reported to be the most burdensome adverse drug reaction according to patients, and can negatively influence drug adherence.
Aims & Methods
Aim: To assess the incidence of all infections and identify risk factors for the development of infections in IBD patients.
Methods: We previously developed and validated a Patient-Reported Infections Questionnaire (PRIQ), with excellent diagnostic accuracy, covering 15 infection categories with a 3-month recall period. [1] The current prospective, multicentre, observational cohort study was performed between Jun, 1 2020 and Jul, 1 2021, enrolling consecutive IBD patients and using the PRIQ which was implemented in myIBDcoach, an established telemedicine platform. Infection severity was defined as mild (self-limiting or topical treatment), moderate (oral antibiotics, antivirals or antifungals) or severe (hospitalization or IV treatment). Incidence rates (IR) were calculated for all infections, stratified for severity and subtype. Multivariable logistic regression, adjusting for relevant confounders, was performed to identify risk factors for infections.
Results
In total, 629 IBD patients (n=346 CD, n=283 UC, 58.3% female, mean age at cohort entry 48.3 years [SD 14.8], mean disease duration 12.4 years [SD 10.8]) were included which completed 2391 PRIQs during 572 person-years (PY) of follow-up. This resulted in 990 reported infections, corresponding to IRs of 17.3, 11.8, 5.1, and 0.4 per 10PY for all, mild, moderate, and severe infections, respectively. Upper respiratory tract (IR 26.9/100PY) and urinary tract infections (IR 14.8/100PY) were the most commonly reported mild and moderate infections types, respectively (Table 1). Compared to patients without treatment, patients on immunosuppressive treatment more frequently experienced infections of any severity (mild vs. no treatment: IR ratio (IRR) 1.57 [95%CI 1.21-2.06] p<0.001, moderate vs. no treatment: IRR 1.42 [95%CI 1.20-1.69] p<0.001). On multivariable logistic regression, female sex (mild adjusted odds ratio [aOR] 1.96 [95%CI 1.38-2.79]; moderate aOR 1.71 [95%CI 1.15-2.54]), smoking status (mild aOR 1.66 [95%CI 1.15-2.41]; moderate aOR 1.86 [95%CI 1.05-3.28]), higher BMI (moderate aOR 1.05 [95%CI 1.02-2.00]), and more comorbidities (mild aOR 2.41 [95%CI 1.46-3.98]; moderate aOR 1.82 [95%CI 1.07-3.11]) were all significantly associated with the development of mild and moderate infections.
Table 1. Incidence rates for all infections, and stratified for infection type and infection severity per 100 PY.
|
|---|
| All infections | Mild infections | Moderate infections | Severe infections |
| Infection type† | n | IR [95% CI] | n | IR [95% CI] | n | IR [95% CI] | n | IR [95% CI] |
All
Influenza
URTI
LRTI
COVID-19
Eye
Oral
Cold sore
Gastrointestinal
Urinary tract
Genital
Skin
Shingles
Warts
Tuberculosis
Meningitis
Hepatitis
Other | 990
131
205
48
46
58
76
102
18
95
33
80
10
68
0
0
3
17 | 173.0 [162.4-184.0]
22.9 [19.2-27.1]
35.8 [31.2-41.0]
8.4 [6.3-11.0]
8.0 [6.0-10.6]
10.1 [7.8-13.0]
13.3 [10.5-16.5]
17.8 [14.6-21.5]
3.1 [1.9-4.9]
16.6 [13.5-20.2]
5.8 [4.0-8.0]
14.0 [11.2-17.3]
1.7 [0.9-3.1]
11.9 [9.3-15.0]
N/A
N/A
0.5 [0.1-1.4]
3.0 [1.8-4.7] | 673
102
154
14
38
53
58
98
2
8
19
50
1
68
0
0
0
8 | 118.0 [108.9-126.7]
17.8 [14.6-21.5]
26.9 [22.9-31.4]
2.4 [1.4-4.0]
6.6 [4.8-9.0]
9.3 [7.0-12.0]
10.1 [7.8-13.0]
17.0 [14.0-20.8]
0.3 [0.06-1.2]
1.4 [0.6-2.7]
3.3 [2.0-5.1]
8.7 [6.6-11.4]
0.2 [0.009-0.9]
11.9 [9.3-15.0]
N/A
N/A
N/A
1.4 [0.6-2.6] | 292
25
48
31
6
5
17
4
8
85
14
30
9
0
0
0
2
8 | 51.0 [45.4-57.1]
4.4 [2.9-6.4]
8.4 [6.3-11.0]
5.4 [3.7-7.6]
1.0 [0.4-2.2]
0.9 [0.3-1.9]
3.0 [1.8-4.7]
0.7 [0.2-1.7]
1.4 [0.6-2.6]
14.8 [12.0-18.3]
2.4 [1.4-4.0]
5.2 [3.6-7.4]
1.6 [0.8-2.9]
N/A
N/A
N/A
0.3 [0.06-1.2]
1.4 [0.6-2.7] | 25
4
3
3
2
0
1
0
8
2
0
0
0
0
0
0
1
1 | 4.0 [2.9-6.4]
0.7 [0.2-1.7]
0.5 [0.1-1.4]
0.5 [0.1-1.4]
0.3 [0.06-1.2]
N/A
0.2 [0.009-0.9]
N/A
1.4 [0.6-2.6]
0.3 [0.06-1.2]
N/A
N/A
N/A
N/A
N/A
N/A
0.2 [0.009-0.9]
0.2 [0.009-0.9] |
n, number of infectious events; IR, incidence rate; PY, person-years; CI, confidence interval; URTI, upper respiratory tract infection; LRTI, lower respiratory tract infection. 95%CI calculated using Mid-P exact test
†Elaboration on infection types: URTI includes nasal cold, laryngitis, tonsillitis, sinus infection, ear infection and ‘common’ cold. LRTI includes pneumonia and bronchitis.
Time at risk (572.5 PY) based on follow up of 629 IBD patients during 1 year. |
Conclusion
In this real-world prospective study, immune suppressive therapy was associated with mild and moderate infections of any kind in IBD patients. These infections particularly occur in females, smokers, patients with higher BMI and more comorbidities. This information should be considered in personalised treatment selection.
References
[1] Rezazadeh Ardabili A, van Esser D, Wintjens D, et al. Development and validation of a remote monitoring tool for assessment of mild, moderate, and severe infections in Inflammatory Bowel Disease [published online ahead of print, 2023 Feb 16]. J Crohns Colitis. 2023;jjad023. doi:10.1093/ecco-jcc/jjad023
Disclosure
M.P. reports grants and non-financial support from Falk Pharma, grants from European commission, grants from ZonMw (Dutch national research fund), grants and non-financial support from Takeda, grants and non-financial support from Johnson and Johnson, grants and non-financial support from Abbvie, non-financial support from Ferring, non-financial support from Immunodiagnostics, non-financial support from MSD, all outside the submitted work. D.J. reports grants from Top Knowledge Institute (Well on Wheat), grants from Horizon 2020 DISCOvERIE, grants from NWO-CCC Partnership program (Carbokinetics), all outside the submitted work. Z.M. reports grants form MLDS, Niels Stensen Fellowship and Galapagos. A.v.B. has served as speaker, adviser and/or principal investigator for AbbVie, Arandal, Arena, Celgene, Ferring, Galapagos, Janssen, MSD, Pfizer, Roche, Takeda, TEVA, and received research grants from Pfizer, TEVA, Eurostars funding, ZonMw, all outside the submitted work.
The other authors have nothing to disclose relevant to this publication.
