Risk of Serious and Opportunistic Infections Associated With Advanced Therapy in Inflammatory Bowel Disease Patients from an Academic Center in Brazil

Background:
The risks of serious and opportunistic infection associated with the various targeted therapies for inflammatory bowel disease (IBD) is one of the main concerns of clinicians whose practices are focused on IBD management. We assessed the incidence and risk factors of serious or opportunistic infections in patients with IBD treated with advanced therapy in a cohort of patients in tertiary IBD center located in Brazil.
Methods:
We performed an ambispective observational study of patients (18 years or older) with a diagnosis of IBD in the University Hospital of Federal University of Juiz de Fora, Brazil. We retrospectively analyzed all the IBD patients from February, 2014 to December 2017 and prospectively analyzed those with IBD from January 2018 to April 2022. Serious infections were defined as those requiring intravenous antibiotic therapy or hospitalization; opportunistic infections (OIs) were defined as infections that normally do not cause a disease, but become pathogenic when the body’s defense system is impaired. 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 and time-varying sociodemographic characteristics, and medications.
Results:
Among the 504 patients with IBD included in our analysis, 75 serious infections and 35 OIs occurred, 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), herpes zoster (n=11), cytomegalovirus (n=2), and Histoplasma capsulatum (n=1). Compared with aminosalicylates, vedolizumab and ustekinumab therapy did not increase the risk of serious and OIs infections (HR, 0.93; 95% CI, 0.42-1.81). Conversely, compared with aminosalicylates, tofacitinib, anti-TNF monotherapy, 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).
Conclusions:
Anti-TNF therapy and combination therapy were associated with an increased risk of serious and OIs compared to non-immunosuppressed patients. Therapy with vedolizumab and ustekinumab appears to present a very low risk of serious and OIs while tofacitinib was associated with a small increased risk of OIs, particularly herpes zoster. Tuberculosis was the main opportunistic infection observed, being a characteristic of countries hyperendemic for this infection, 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 and OIs and weighed against potential benefits of the various targeted therapies for IBD management. *This study was partially funded by National Council for Scientific and Technological Development – CNPq.