Clinical Response and Complications Are Not Associated with Level of Cyclosporine in Patients with Severe Ulcerative Colitis

Abstract

Introduction: Cylclosporine (CyA) salvage therapy is effective in patients with steroid refractory ulcerative colitis (UC). The optimal drug level to achieve response and minimize complications during induction therapy, however, is not known. Methods: We conducted a retrospective analysis of consecutive hospitalized patients with steroid refractory UC treated with CyA in a single tertiary care center from 5/2008 to 6/2015. Data was collected on baseline demographics, previous medication usage, and laboratory values during hospitalization. Outcomes of colectomy within 90 days and post-operative complications (infectious and non-infectious) for patients who had surgery during their initial hospitalization were compared by first, mean, and peak CyA level while in the hospital both as continuous variables and grouped by quartile. Results: A total of 81 patients with severe UC started on IV CyA were included in the analysis. Median age of cohort was 34 years. 47 patients (58%) required a colectomy within 90 days of starting CyA. Patients who responded to CyA and did not require surgery within 90 days had significantly lower C-Reactive Peptide levels (2.0 mg/L vs 3.8 mg/L, p= 0.01), higher serum albumin (3.7g/dL vs. 3.4 g/dL, p=0.03) at baseline and were more likely to have been treated with anti-TNF agents previously (33.4% vs 4.3%, p=0.0001). There were no differences between initial, mean and peak CyA levels among responders and non-responders. 37 patients (45.6 %) underwent surgery of which 10 patients (27%) had post operative complications. There was also no association with response or post-operative complications in an interquartile analysis of first ( <177, 177-263, 264-330, >331) mean ( < 237,237-277, 278-354, >355), and peak ( < 347,347-418,419-490, >490) CyA (ng/mL) levels. Conclusion: In this single center analysis, clinical response and post-operative complications were not associated with level of cyclosporine during IV induction therapy. As there were few patients in the cohort with a mean level less than 200ng/mL during IV therapy, this analysis was limited in assessing response and safety in a population with targeted dosing of low levels of cyclosporine.Table 1: Risk of Colectomy and Complications by Inter-quartile Cyclosporine Levels