Evaluation of Histologic and Endoscopic Remission Induced by Infliximab in Moderate to Severe Ulcerative Colitis (HERICA)

• histological remission [ Time Frame: histological remission were assessed at week 8 ] [ Designated as safety issue: No ]
  To assess if infliximab is able to induce histological remission in patients with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy, including corticosteroids and 6-MP/AZA or who are intolerant or have medical contraindications for such therapies using Geboes criteria at week 8
  
  
• Clinical response [ Time Frame: clinical response were assessed at week 8 ] [ Designated as safety issue: No ]
  To assess the clinical response in the above patients assessed by Mayo Score at week 8
  
  

• Histologic Efficacy assessment [ Time Frame: baseline, week 8, week 30 and week 52. ] [ Designated as safety issue: No ]
  To assess the impact of infliximab histologically, four biopsies will be collected from distinct areas (two from rectum and two from sigmoid) from each patient
  
  
• Correlate histological remission with mucosal healing,faecal calprotectin and lactoferrin levels,number of colectomies,number of hospitalizations,Number of clinical relapses [ Time Frame: up to week 52 ] [ Designated as safety issue: No ]

  Correlate histological remission with:

  Mucosal healing Faecal calprotectin and lactoferrin levels Number of colectomies up to week 52 Number of hospitalizations up to week 52 Number of clinical relapses up to week 52

  
  

Correlations between histologic disease activity and other assessments of clinical disease activity are not well established despite a good correlation being found between endoscopy and histology, especially during active ulcerative colitis (1,2). Endoscopic healing induced by infliximab in Crohn's disease patients was associated with a significant reduction in surgeries and hospitalizations (3). Histological recovery in ulcerative colitis is often incomplete and some studies have shown that microscopic evidence of inflammation is common even in patients with clinically and quiescent colitis assessed by sigmoidoscopy (4,5). Although this fact has not yet been completely elucidated, it is suggested that some patients with residual microscopic acute inflammation may be more prone to relapse (2). The prognostic importance of microscopic inflammation is unknown. Given that the rectum is always involved in ulcerative colitis and inflammatory activity is diffuse and restricted to the mucosa, the collection of samples from the rectal and sigmoid mucosa are potentially useful tools for evaluating disease severity. In addition, there is a strong correlation between the levels of calprotectin and the degree of inflammation as assessed by endoscopic and histologic criteria (6). Therefore, the measurement of faecal calprotectin and lactoferrin may also provide as valuable non-invasive tools to assess disease activity and optimize the treatment in UC patients.

Histologically, active disease is defined by the presence of neutrophils in conjunction with epithelial cell damage. Analysis generally relies on the examination of H & E-stained sections. Two samples are suggested as more appropriated because it is well-known that treatment may induce variations in the expression of inflammation intensity. Several histological scores were proposed, however, Geboes index (7) has been validated and tested for reproducibility and has 5 domains: structural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulceration. The Geboes index has a more elaborated grading of crypt lesions and surface epithelial damage than other proposed indexes. The aim of this study is to assess the relationship between microscopic Geboes index of inflammation and clinical course of ulcerative colitis in patients treated with infliximab. The investigators propose to test the hypothesis if infliximab is able to induce histological remission and then change the clinical course of ulcerative colitis