Risk of serious infections in patients with inflammatory bowel disease treated with biologic and small molecule therapies: A nationwide cohort study

Abstract Background We aimed to assess the risk of serious infections in patients with inflammatory bowel disease (IBD) exposed to different advanced therapies. Methods We linked nationwide registers and compared rates of incident serious infections in patients with Crohn’s disease (CD) and ulcerative colitis (UC) exposed to medical therapies versus matched general population comparators during 2007 to 2023. We 1:1 propensity score-matched individuals with IBD to compare infection risk across therapies. Results We identified 55,866 patients with IBD naïve to immunomodulators (IMM) and advanced therapies, 20,392 exposed to IMM, 15,973 to anti-TNF, 9035 to IMM with anti-TNF, 3948 to vedolizumab, 2926 to ustekinumab, 659 to tofacitinib, 987 to upadacitinib, 262 to filgotinib, and 163 to risankizumab with 987,366 matched comparators with up to 18 years of follow-up. Compared to the general population [incidence rate range 0.39-1.13 per 100 person-years (PY)], patients with IBD had a higher incidence of serious infections [naïve 2.31 per 100 PY; adjusted hazard ratio (aHR) 1.89, 95% Confidence Interval (CI) 1.84-1.94], IMM 3.27 per 100 PY (aHR 4.45 95% CI 4.24-4.66), advanced therapies range 3.14-8.10 per 100 PY (aHRs range 3.45-10.55, 95% CI range 3.04-26.65). Relative risks were elevated in the pediatric population, and for opportunistic and gastrointestinal infections. No differences in infection rates were observed in propensity score-matched comparisons of different advanced therapies. Conclusion Patients with IBD were at an increased risk of infections, even among those naïve to IMM and advanced therapies. There was no significant difference in risk of infections across advanced therapy exposures.