Granulomatous Opportunistic Infections in a Tertiary IBD Center Located in a Tuberculosis Hyperendemic Region in Brazil
AIBD 2023
Background:
The risk of granulomatous opportunistic infection associated with the various targeted therapies for inflammatory bowel disease (IBD) remains unclear. We assessed the incidence and risk of granulomatous infections in patients with IBD treated with advanced in a cohort of patients in tertiary IBD center located in a tuberculosis hyperendemic region in Brazil.
Methods:
We performed a retrospective cohort 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 collected data from February, 2014 until April 2022. The incidence (per 1000 patient-years) and risks of granulomatous infections associated with exposure to combination therapy (anti-TNF and thiopurines), monotherapies with anti-TNF, vedolizumab, ustekinumab or tofacitinib were compared using marginal structural Cox proportional hazard models adjusted for baseline and time-varying sociodemographic characteristics, and medications.
Results:
Among the 1,345 patients with IBD included in our analysis, 35 granulomatous opportunistic infections occurred, resulting in incidence rates of 3.3 per 1000 PY. Overall incidence rates of granulomatous infections ranged from 0.3, 6.7, and 12.1 per 1000 PY in those exposed to ustekinumab monotherapy, anti-TNF monotherapy, and combination therapy, respectively. There was no case of granulomatous infection in patients exposed to vedolizumab or tofacitinib. In incident patients, granulomatous infections occurred after a mean duration of 170 (SD, 143), and 125 (SD, 98) days of exposure to anti-TNF monotherapy and combination therapy, respectively. Granulomatous infections were mostly due to Mycobacterium tuberculosis (91.4%), and Histoplasma capsulatum (8.6%). One patient with granulomatous infection (2.8%) died within 1 month after infection onset due to pulmonary embolism. Compared with anti-TNF monotherapy and ustekinumab monotherapy, combination therapy was associated with increased risks of granulomatous infection (HR, 1.93; 95% CI, 1.42-4.81 and HR, 38.3; 95% CI, 19.21-40.53, respectively). Compared with ustekinumab monotherapy, anti-TNF monotherapy was associated with increased risk of granulomatous infection (HR, 21.51; 95% CI, 12.56-29.78) and, specifically, mycobacterial infection (HR, 19.58; 95% CI, 12.13-27.50).
Conclusions:
In a cohort study of patients with IBD in a tertiary center located in a tuberculosis hyperendemic region in Brazil, we found that anti-TNF therapy was associated with a higher incidence and risk of granulomatous infections, particularly tuberculosis compared with non-TNF blocking biological agents or with tofacitinib. The odds of developing tuberculosis were nearly 20 times greater for patients using anti-TNF agents compared with those on ustekinumab. Therapy with vedolizumab and/or tofacitinib appears present a very low risk of granulomatous infections. In choosing targeted therapy for IBD, clinicians should consider, among other factors, the risk of granulomatous opportunistic infections and weighed against potential benefits of the various advanced therapies for IBD management. *This study was partially funded by National Council for Scientific and Technological Development – CNPq.
