Gene expression changes associated with resistance to intravenous corticosteroid therapy in children with severe ulcerative colitis

Although corticosteroids remain a mainstay of therapy for UC, a meta-regression of cohort studies in acute severe ulcerative colitis (UC) showed that 29% of patients fail corticosteroid therapy and require escalation of medical management or colectomy. We aimed to determine whether genes expressed in whole blood early following initiation of intravenous corticosteroid treatment can be associated with response. 20 corticosteroid responsive (PUCAI < 35 by day 5) and 20 corticosteroid resistant patients (PUCAI ≥ 35 by day 5 and need for 2nd line medical therapy or colectomy by hospital discharge) were selected from a prospectively accrued cohort of patients hospitalized for intravenous corticosteroid treatment of severe UC. Total RNA was extracted from blood samples collected on day 3 of intravenous corticosteroid therapy. The eluted transcriptomes were quantified on Affymetrix Human Gene 1.0 ST arrays. The data was analysed by the local-pooled error method for discovery of differential gene expression and false discovery rate correction was applied to adjust for multiple comparisons. P-values less than 0.05 after correction were considered significant.