S879 Risk of Opportunistic Infections Among Inflammatory Bowel Disease Patients on Biologics: A Nationwide Database Study

Introduction: Biological therapy in IBD, particularly TNF-alpha inhibitor, has been associated with an increased risk of serious infections such as pneumonia, zoster, tuberculosis, and opportunistic infection. However available data regarding some opportunistic infections are conflicting as some of these studies are small and confounded by the simultaneous use of several immunosuppressive agents. Our study aimed to assess the risk of various opportunistic infections among IBD patients treated with biologics, utilizing a large database. Methods: We conducted a retrospective cohort study using the TrinNetX database, a multi-institutional database, that included all adult patients (18 years and older) diagnosed with IBD (CD or UC) on biological therapy (infliximab, adalimumab, golimumab, certolizumab, vedolizumab, natalizumab, or ustekinumab), as well as patients not treated with biological therapy. The aim was to compare the risk of selected infectious diseases between the 2 groups, at least 1 month after therapy initiation. To minimize confounding and ensure balanced groups, we employed 1:1 propensity score matching for factors such as age, gender, race, tobacco use, alcohol use, diabetes, HIV, organ transplant, and medications including azathioprine, mercaptopurine, methotrexate, 5-ASA medications, and steroids. Results: After matching, there were 79,960 IBD patients in each cohort. Patients on biologics had a higher risk of Legionella (OR 2.85, 95% CI 1.55-5.25, P 0.0004), Tuberculosis (OR 1.98, 95% CI 1.60-2.45, P < 0.0001), Clostridioides difficile (OR 1.85, 95% CI 1.75-1.95, P < 0.0001), sepsis (OR 1.11, 95% CI 1.05-1.16, P < 0.0001), Histoplasmosis (OR 2.66, 95% CI 1.81-3.91, P < 0.0001), Candidiasis (OR 1.22, 95% CI 1.17-1.28, P < 0.0001), CMV (OR 1.21, 95% CI 1.05-1.40, P 0.0062), HSV (OR 1.11, 95% CI 1.03-1.20, P 0.0040), and VZV (OR 1.28, 95% CI 1.195-1.38, P < 0.0001) infections compared to those not on biologics. The risk of Streptococcus pneumoniae pneumonia, Actinomycosis, Nocardiosis, Cryptococcosis, Aspergillosis, Pneumocystis, influenza, and HPV was not significantly different between the 2 cohorts (Table 1). Conclusion: Our study revealed that IBD patients on biologics are at a higher risk of certain opportunistic infections compared to those not treated with biologics. This study underscores the importance of close monitoring for infections in IBD patients on biologics, particularly for those at high risk. Table 1. - Risk of Selected Opportunistic Infections in IBD Patients on Biologics vs No Biologics Outcome IBD on biologicsN=79,960 IBD not on biologicsN=79,960 OR 95% CI P-value Bacterial Legionella 40 (0.05%) 14 (0.02%) 2.858 (1.555,5.253) 0.0004 Streptococcus pneumoniae pneumonia 77 (0.1%) 81 (0.1%) 0.951 (0.696,1.299) 0.6691 Tuberculosis 256 (0.32%) 129 (0.16%) 1.988 (1.608,2.457) < 0.0001 Nocardiosis 20 (0.03%) 19 (0.02%) 1.053 (0.562,1.972) 0.8728 Actinomycosis 52 (0.06%) 38 (0.05%) 1.369 (0.901,2.08) 0.1399 Clostridioides difficile 3,704 (4.63%) 2,045 (2.56%) 1.851 (1.752,1.955) < 0.0001 Sepsis 3,583 (4.48%) 3,245 (4.06%) 1.109 (1.056,1.164) < 0.0001 Fungal Histoplasmosis 96 (0.12%) 36 (0.05%) 2.669 (1.819,3.915) < 0.0001 Cryptococcosis 16 (0.02%) 19 (0.02%) 0.842 (0.433,1.638) 0.6121 Aspergillosis 89 (0.11%) 88 (0.11%) 1.011 (0.753,1.358) 0.9401 Candidiasis 4,329 (5.41%) 3,563 (4.46%) 1.227 (1.173,1.284) < 0.0001 Pneumocystis 48 (0.06%) 41 (0.05%) 1.171 (0.772,1.776) 0.4580 Viral Human Papillomavirus (HPV) 460 (0.58%) 465 (0.58%) 0.989 (0.869,1.126) 0.8690 Influenza 1,446 (1.81%) 1,518 (1.9%) 0.952 (0.885,1.023) 0.1819 Cytomegalovirus (CMV) 426 (0.53%) 349 (0.47%) 1.219 ((1.058,1.405)) 0.0062 Herpes Simplex Virus (HSV) 1,436 (1.79%) 1,286 (1.61%) 1.118 (1.036,1.202) 0.0040 Varicella-Zoster Virus (VZV) 1,680 (2.1%) 1,313 (1.64%) 1.286 (1.195,1.383) < 0.0001