Infliximab Results in Reduction of Inflammation and Inflammatory Markers in the Mucosa of Ulcerative Colitis Patients

Abstract

Purpose: In ACT 1, effects of infliximab (IFX) on histological inflammatory activity and inflammatory markers in colonic mucosa of ulcerative colitis (UC) pts was assessed. Methods: 364 pts with moderately-to-severely active UC (endoscopy score≥2, Mayo score 6–12) despite corticosteroids or AZA /6-MP were randomized to placebo (PBO), IFX 5 mg/kg, or IFX 10 mg/kg at wks 0, 2, 6, 14, and 22. The primary endpoint was clinical response at wk 8 (decrease in Mayo score of ≥30% and ≥3 points, with a decrease in rectal bleeding score of ≥1 or rectal bleeding score of 0 or 1, at wk 8). Colonic biopsies were collected at wks 0, 8, and 30 and formalin-fixed from ∼35 pts per group. Hemotoxylin & eosin-stained sections were scored for inflammation severity by a blinded pathologist. HLA-DR, tenascin, CD3, myeloproxidase (MPO), and gelatinase B (MMP-9) expression was evaluated by immunohistochemistry. Results: Baseline biopsies had histological features of inflammation characterized by neutrophils in the epithelium, crypt destruction, or the presence of ulcers and erosions (grade 3–5) (63.6%[PBO]; 76.4%[combined IFX]) with ∼ 11.9% with structural change only. At wks 8 and 30, 35% of IFX and 24% of PBO pts showed structural change unaccompanied by inflammatory changes (grade 0) which equals healing. These histological changes were accompanied by decreased expression of proinflammatory mediators that were more pronounced in the combined IFX group vs PBO (Table 1).Table 1: Inflammatory Marker ExpressionConclusions: IFX promotes histological healing and down regulation of inflammatory changes. IFX induced down regulation of HLA-DR, tenascin, and CD3-, MPO- and MMP-9-positive cells at wk 8; only tenascin (indicating normal mucosa) and CD3 expression differed from PBO at wk 30.