P1163 Treatment-based risk stratification of serious and opportunistic infections in IBD patients from an tertiary center in brazil: a comparison between advanced therapies and non-biologic exposure in real world setting

Abstract Background The risks of serious and opportunistic (OIs) infections associated with advanced therapies for IBD is one of the main concerns of both physicians and advanced practice clinicians in IBD care. We assessed the incidence and stratify the risk of serious infections or OIs in patients with IBD treated with advanced therapy. Methods We performed an ambispective observational study of adults patients with a diagnosis of IBD in a tertiary IBD center located in Brazil. We retrospectively analyzed the IBD patients from 2014 to 2017 and prospectively those from 2018 to 2022. Serious infections were defined as those requiring intravenous antibiotic therapy or hospitalization. The incidence (per 100 patient-years) and risks of serious and OIs associated with exposure to combination therapy (anti-TNF and thiopurines), monotherapies with anti-TNF, vedolizumab, ustekinumab or tofacitinib were compared with exposure to aminosalicylates using marginal structural Cox proportional hazard models adjusted for baseline characteristics and medications. Results Among the 504 patients, 75 serious infections and 35 OIs were observed, resulting in overall incidence rates of serious infections and OIs of 3.1 and 1.1 per 100 PY, respectively. Overall incidence rates of serious infections ranged from 0.1, 0.15, 0.13, 0.16, 1.2., and 3.1 per 100 PY in those exposed to aminosalicylates, ustekinumab, vedolizumab, tofacitinib, anti-TNF monotherapy, and combination therapy, respectively. Conversely, the overall incidence rates of OIs ranged from 0, 0.1, 0.1, 0.3, 0.9, and 2.1 per 100 PY in those exposed to aminosalicylates, ustekinumab, vedolizumab, tofacitinib, anti-TNF monotherapy, and combination therapy, respectively. OIs were mostly due to Mycobacterium tuberculosis (n=21) and herpes zoster (n=11). Compared with aminosalicylates, vedolizumab and ustekinumab therapy did not increase the risk of serious infections and OIs (HR, 0.93; 95% CI, 0.42-1.81). Conversely, tofacitinib, anti-TNF monotherapy and combination therapy were associated with increased risks of OIs (HR, 1.13; 95% CI, 1.05-2.01), HR, 2.13; 95% CI, 1.92-5.81 and HR, 32.3; 95% CI, 19.21-40.53, respectively). Conclusion Anti-TNF therapy and combotherapy were associated with an increased risk of serious infections and OIs, while vedolizumab and ustekinumab presented a insignificant risk of these infections. Tofacitinib was associated with a small increased risk of OIs. Tuberculosis was the main OI, and was associated exclusively with the use of anti-TNF monotherapy or combotherapy. In choosing advanced therapy for IBD, clinicians should consider, among other factors, the risk of serious infections and OIs and weighed against potential benefits of the various targeted therapies for IBD. References 1.José da Silva R, da Rocha Ribeiro TC, Chebli LA, Chebli JMF. An Unexpected Cause of Headache and Splenic Lesions During Anti-TNF Therapy in Crohn Disease. Inflamm Bowel Dis. 2021; 27(1):e1-e2. 2.Bonovas S, Fiorino G, Allocca M, Lytras T, Nikolopoulos GK, Peyrin-Biroulet L, Danese S. Biologic Therapies and Risk of Infection and Malignancy in Patients With Inflammatory Bowel Disease: A Systematic Review and Network Meta-analysis. Clin Gastroenterol Hepatol. 2016;14:1385-1397.e10. 3.Singh S, Facciorusso A, Dulai PS, Jairath V, Sandborn WJ. Comparative Risk of Serious Infections With Biologic and/or Immunosuppressive Therapy in Patients With Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis. Clin Gastroenterol Hepatol. 2020;18:69-81.e3. 4.Solitano V, Facciorusso A, Jess T, Ma C, Hassan C, Repici A, Jairath V, Armuzzi A, Singh S. Comparative Risk of Serious Infections With Biologic Agents and Oral Small Molecules in Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis. Clin Gastroenterol Hepatol. 2023;21(4):907-921.e2