Histology grade has the strongest association with the risk of clinical relapse in patients with UC who are in clinical remission. Consideration should be given to including this end point in evaluating therapy for UC.

Background & Aims Mucosal healing, based on histologic analysis, is an endpoint of maintenance therapy for patients with ulcerative colitis (UC). There are few data on how histologic signs of inflammation correlate with endoscopic and peripheral blood measures of inflammation in these patients. We investigated patterns of histologic features of inflammation in patients with UC in clinical remission, and correlated these with endoscopic and biochemical measures of inflammation. Methods We performed a prospective observational study of 103 patients with UC in clinical remission undergoing surveillance colonoscopy while receiving maintenance therapy with mesalamine or thiopurines; 2674 biopsies were collected from 708 colonic segments. Each colonic segment was evaluated based on the Mayo endoscopic sub-score and the Geboes histology score (0–5.4). Biomarkers were measured in peripheral blood samples. Results Histologic features of inflammation were found in 54% of patients receiving maintenance therapy; 37% had at least moderate inflammation, based on histology scores. Of the 52 patients with endoscopic evidence only of left-sided colitis, 34% had histologic features of inflammation in their proximal colon. Histology scores correlated with endoscopic scores for per-segment inflammation (Spearman’s ρ=0.65; P<.001). Patients with histology scores >3.1 had a significantly higher mean level of C-reactive protein (CRP) than those with scores <3.1. There were no differences among treatment groups in percentages of patients with histologic scores >3.1. Conclusions Patients in clinical remission from UC still frequently have histologic features of inflammation, which correlate with endoscopic appearance. Patients with at least moderate levels of inflammation, based on histologic grading (score >3.1), have higher serum levels of CRP, which could be used as a surrogate marker of histologic inflammation.

Objectives Patients with ulcerative colitis (UC) who are in clinical remission may still have underlying endoscopic inflammation, which is associated with inferior clinical outcomes. The goal of this study was to determine the prevalence of, and factors associated with, active endoscopic disease in patients with UC who are in clinical remission. Design Prospective observational study in a single center. Patients with UC in clinical remission (by SCCAI) were enrolled prospectively at time of surveillance colonoscopy. Disease phenotype, endoscopic activity (Mayo sub-score) and histological score (Geboes) were recorded, and blood was drawn for peripheral blood biomarkers. Results 149 patients in clinical remission were prospectively enrolled in this cohort; 81% had been in clinical remission for > 6 months, and 86% were currently prescribed maintenance medications. At endoscopy 45% of patients in clinical remission had any endoscopic inflammation (Mayo endoscopy sub-score >0) and 13% had scores >1. In a multivariate model, variables independently associated with a Mayo endoscopic score >1 were remission for < 6 months (p=.001), WBC (p=0.01) and CRP (p=0.009). A model combining these three variables had a sensitivity of 94% and a specificity of 73% for predicting moderate-severe endoscopic activity in patients in clinical remission (AUC 0.86). In an unselected sub-group of patients who had peripheral blood mononuclear cell mRNA profiling, GATA3 mRNA levels were significantly higher in patients with endoscopic activity. Conclusions Duration of clinical remission, WCC and CRP can predict the probability of on-going endoscopic activity despite clinical remission in patients with UC. These parameters could be used to identify patients who require intensification of treatment to achieve mucosal healing.

BACKGROUND & AIMS Vitamin D levels have been associated with disease activity in patients with ulcerative colitis (UC), but it is unclear whether they affect the risk of disease relapse. We sought to determine the association between baseline vitamin D levels during a period of clinical remission and risk of subsequent UC relapse. METHODS We performed a physician-blinded prospective study of 70 patients with UC in clinical remission followed after a surveillance colonoscopy at a tertiary academic medical center. Serum samples were collected at the time of colonoscopy and baseline endoscopic and histologic activity were determined. Levels of 25-hydroxy-vitamin D were measured using an ELISA. The primary outcome was rate of clinical relapse, determined over 12 months. RESULTS The mean baseline vitamin D level was lower among patients with relapse (29.5 ng/mL) than without (50.3 ng/mL) (P=.001). Remission vitamin D level (≤ 35 ng/mL) was associated with risk of clinical relapse (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.01–1.56; P=.044) over 12 months, independent of endoscopic or histologic grade at enrollment. A receiver operating characteristic curve of vitamin D levels for the outcome of relapse had an area under the curve of 0.72; a serum level ≤ 35 ng/mL had a sensitivity of 70% (95% CI 46%–88%) and specificity of 74% (95% CI 57%-83%) for predicting risk of clinical relapse. CONCLUSIONS Serum levels of vitamin D ≤ 35 ng/mL during periods of clinical remission increase the risk of UC relapse. Clinical trials to obtain vitamin D levels above this threshold should be considered.

Inflammatory bowel disease (IBD) is comprised of Crohn's disease and ulcerative colitis, both chronic inflammatory intestinal disorders of unknown etiology characterized by a waxing and waning clinical course. For many years, the drug therapy was limited to sulfasalazine and related aminosalicylates, corticosteroids and antibiotics. Studies suggesting that the pathophysiology of these disorders relates to a disregulated, over-active immune response to indigenous bacteria have led to the increasing importance of immunosuppressive drugs for the therapy of IBD. This review details the mechanisms of action, clinical efficacy, and adverse effects of these agents.