Patients with Acute Severe Ulcerative Colitis Treated with IV Cyclosporine Who Require Colectomy Within 3 Months of Discharge Have Lower Serum Cyclosporine Levels

Abstract

Abstract Background: Cyclosporine (CYS) is a calcineurin inhibitor commonly used as induction therapy in steroid-refractory patients with acute severe ulcerative colitis (ASUC) during hospitalization. Aim: To identify the relationship between post-hospitalization CYS serum levels and adverse clinical outcomes. Methods: Electronic medical records of patients with established diagnosis of UC hospitalized for ASUC discharged on oral CYS following IV CYS induction between May 2013 to December 2017 were retrospectively analyzed. Results: Of thirty-nine patients, five patients underwent colectomy during initial hospitalization; thirty-four remaining patients were analyzed. Twenty patients experienced CYS-related adverse events (AEs); five patients were dose-reduced and three patients were discontinued. CYS dose-reduced or discontinued patients were significantly more likely to have undergone colectomy within three months (62.5% vs 11.5%, p=0.009). Fifteen (44%) total patients who underwent colectomy within one year post-hospitalization; eight (23.5%) patients underwent colectomy within three months. Logistic regression analysis adjusting for age, sex, weight, albumin, CRP and AEs demonstrated subtherapeutic serum CYS level (<200 ng/mL) was independently associated with increased risk of three-month colectomy (aHR 20.95, 95% CI 1.5-284, p=0.02). Adjusting the model for selective inclusion of AEs requiring dose adjustment or discontinuation, subtherapeutic CYS levels remained independently associated with three-month colectomy (aHR 14.9, 95% CI 1.12-198.9, p=0.02). No significant differences in CYS levels or clinical characteristics in patients who underwent one-year colectomy were observed. Conclusions: We demonstrate independent association of subtherapeutic serum CYS levels following conversion to oral therapy with an increased risk of three-month colectomy, but not with one-year colectomy.