Introduction: The incidence of immune-related adverse events (irAEs) is increasing due to the rapid expansion of immune-checkpoints inhibitors (ICIs) use. Recent studies showed that immune-related colitis (IRC) is the most common high-grade irAE. However, limited data are available regarding the clinical course and outcomes of severe and life-threatening (CTCAE grade ≥3) IRC. Therefore, we conducted a retrospective cohort study exploring the characteristics, treatment course, and outcomes of high-grade IRC.
Methods: At our tertiary care hospital, we established the ITOX service; one of the first inpatient services in the country devoted to mitigating irAEs. We then incorporated a novel platform into the electronic medical record (Epic) to triage patients admitted with irAEs to the ITOX service. We reviewed the charts of patients admitted to the ITOX service with high-grade IRC within the last year and collected clinical, endoscopic, and histopathological data.
Results: A total of 59 patients admitted to the hospital with CTCAE grade≥3 colitis since the ITOX service inception. A 59% of the cohort received ICI monotherapy; 14% received a combined ICI therapy, and 27% received a combination of ICIs and non-ICIs. Thirteen patients (22%) had multiple irAEs and 78% had IRC only at the time of presentation. Imaging studies showed wall thickening, mucosal hyperemia, and air-fluid level. Endoscopy findings range from normal to severe inflammation with deep mucosal ulcerations. The biopsy results showed regenerative changes, increased epithelial cell apoptosis, and intraepithelial lymphocytosis. Most patients 90% had a sustained response to steroids and deemed steroid-sensitive; 1mg/kg/day (74%), >1mg/kg/day (7%), and < 1mg/kg/day (9%). Only 10% of the patients had steroids-refractory IRC and needed other immunosuppressants. The presence of deep ulcerations and erosions associated with steroids-refractory IRC. Most patients (93%) were discharged on steroids. The average length of hospital stay was 15 days, with a readmission rate of 71% within a year with relapsed IRC. One-third (33%) of the patients resumed ICIs after the resolution of high-grade IRC as maintenance therapy or a rechallenge due to disease progression.
Discussion: High-grade IRC is associated with high-risk endoscopic and histopathological features and high rates of hospital readmission. These features could represent markers of disease severity and can be utilized to guide the use of high-dose steroids and other immunosuppressants.
