Advanced IBD Treatments and Serious Infection Risk
Advanced IBD Treatments and Serious Infection Risk
April 7, 2026
Issue 07
Clinical Question
What is the risk of serious infections with biologics and advanced small molecules?
Editor’s Bottom Line
Patients with IBD are at increased risk of serious infection, even when naïve to therapy. Among treated patients, the infection risk did not differ by class of IBD therapy.
Reference
Axelrad J, Forss A, Söderling J, et al. Risk of serious infections in patients with inflammatory bowel disease treated with biologic and small molecule therapies: a nationwide cohort study. J Crohns Colitis. 2026;20(2):jjaf229. https://doi.org/10.1093/ecco-jcc/jjaf229
Synopsis
The researchers linked nationwide Swedish registries to quantify absolute and relative risks of serious infections across inflammatory bowel disease (IBD) treatment exposures compared to individually matched general population comparators, and to compare infection risk across advanced therapies in propensity score-matched IBD cohorts.
The study population included 110,211 patients with Crohn’s disease or ulcerative colitis identified via the Swedish National Patient Register between 2007 and 2023, matched 1:10 to 987,366 general population comparators by age, sex and place of residence.
Therapy groups included patients naïve to immunomodulators (IMM) and advanced therapies (n=55,866), as well as those exposed to IMM (n=20,392), anti-TNF monotherapy (n=15,973), IMM/anti-TNF combination therapy (n=9,035), vedolizumab (n=3,948), ustekinumab (n=2,926), tofacitinib (n=659), upadacitinib (n=987), filgotinib (n=262) and risankizumab (n=163), contributing 146,264 IBD exposure periods with up to 18 years of follow-up.
The primary outcome was first serious infection, defined as hospitalization with an infection as the primary or contributory diagnosis. Secondary outcomes included infection by type. For head-to-head comparisons, 1:1 nearest-neighbor propensity score matching was performed, incorporating sex, age, disease duration, education level, comorbidities, prior hospitalizations, IBD outpatient visits, prescription drug burden, prior serious infection, corticosteroid use and prior IMM or advanced therapy exposure.
Analysis showed that IBD patients naïve to IMM and advanced therapies had an incidence of serious infections significantly higher than the general population (2.31 vs. 1.13 per 100 person-years [PY]; adjusted hazard ratio [aHR]: 1.89; 95% Confidence Interval [CI], 1.84–1.94; number needed to harm [NNH] 85). Infection rates increased with treatment exposure: IMM use was associated with an infection rate of 3.27/100 PY (aHR: 4.45; 95% CI, 4.24–4.66; NNH 40), anti-TNF monotherapy was linked with a rate of 3.14/100 PY (aHR: 4.82; 95% CI, 4.54–5.12; NNH 40), while combination IMM/anti-TNF was associated with a rate of 3.41/100 PY (aHR: 5.69; 95% CI, 5.14–6.29; NNH 35).
Parsing the data by medications, serious infection rates were 3.36/100 PY for vedolizumab (aHR: 3.45; 95% CI, 3.04–3.92; NNH 40), 3.62/100 PY for ustekinumab (aHR: 4.78; 95% CI, 4.03–5.66; NNH 35), 3.61/100 PY for tofacitinib (aHR: 4.55; 95% CI, 3.09–6.70; NNH 35), 4.93/100 PY for upadacitinib (aHR: 5.40; 95% CI, 3.68–7.94; NNH 25), 3.67/100 PY for filgotinib (aHR: 9.98; 95% CI, 2.77–26.42; NNH 30) and 8.10/100 PY for risankizumab (aHR: 10.55; 95% CI, 4.17–26.65; NNH 13).
Pediatric patients younger than 18 years of age had particularly elevated relative risks compared to matched general population comparators, notably for combination IMM/anti-TNF (aHR: 9.97; 95% CI, 7.69–12.93), vedolizumab (aHR: 10.02; 95% CI, 5.04–19.93), and ustekinumab (aHR: 14.79; 95% CI, 6.34–34.52). Absolute incidence rate differences and NNHs, however, were broadly similar across pediatric and elderly patients exposed to advanced therapies.
Stratifying by infection type, the highest relative risks were for opportunistic infections (aHR range: 2.13–11.47) and gastrointestinal infections (aHR range: 3.78–14.97), while the largest absolute incidence rate differences were observed for pneumonia (NNH range: 400–163) and gastrointestinal infections (NNH range: 227–64).
In propensity score-matched head-to-head analyses, serious infection rates did not differ significantly across advanced therapy comparisons and results were consistent when stratified by CD and UC subgroups.
Details
Study Design: Nationwide population-based cohort study
Funding: Crohn’s and Colitis Foundation; National Institutes of Health; Judith & Stewart Colton Center for Autoimmunity; Swedish Research Council; Region Stockholm/Karolinska Institutet ALF grant; Bengt Ihre Fellowship
Allocation: No randomization. Propensity score matching for within-IBD treatment comparisons
Setting: Multicenter
Level of Evidence: 2b