and endoscopic healing (endoscopic score of 0 or 1). Baseline characteristics of the patients in both ACT-1 and ACT-2 were very similar in both trials. More than half of patients (56%) entered the trials on steroid therapy (60% on prednisolone <20 mg) and less than half were on immunosuppressives (46%). Early discontinuation, mostly due to aggravation of colitis, occurred twice as frequently in placebo-treated patients. Table 4 | Mayo scoring system for active ulcerative colitis (reproduced with permission from Schroeder et al. N Engl J Med. 1987;317:1625–1629. Copyright © 1987 Massachusetts Medical Society. All rights reserved.) Score Stool frequency Description 2 3 Rectal bleedinga 3 Blood alone passed Mucosal appearance Normal number of stools for this patient 1–2 stools more than normal 3–4 stools more than normal 5 or more stools than normal No blood seen Streaks of blood with stool less than half of the time Obvious blood with stool most of the time Normal or inactive disease Mild disease (erythema, decreased vascular pattern, mild friability) Moderate disease (marked erythema, absent vascular pattern, friability, erosions) 3 Severe disease (spontaneous bleeding, ulceration) Physician’s global assessment Normal Mild disease Moderate disease Severe disease aMost severe bleeding of the day determines the score. In ACT-1, the clinical response at week 8 (following a three-dose induction with infliximab) was 69% and 62% for patients receiving infliximab 5 and 10 mg/kg, respectively, compared with 37% of those receiving placebo (P<0.005 for both comparisons). In ACT-2, very similar results were obtained, with 65% and 69% of patients receiving infliximab 5 and 10 mg/kg, respectively, achieving a clinical response at week 8, compared with 26% in the placebo group (P<0.001 for both comparisons). In both studies, the proportion of patients who achieved clinical response at weeks 8, 30, or 54 (ACT-1) or clinical remission at weeks 30 or 54 (ACT-1) was several-fold higher among infliximab-treated patients than placebo-treated patients. At week 54, 16% of patients on placebo, 35% on infliximab 5 mg/kg, and 34% on 10 mg/kg were in remission (P=0.001 for both comparisons). Sustained remission at week 8, 30, and 54 was observed in fewer patients, but again significant differences were observed between Core Evidence 2007;2(3) 0 1 0 1 2 0 1 2 0 1 2 3 Infliximab | place in therapy review the placebo- (7%) and infliximab-treated groups (20%) in ACT-1. Endoscopic mucosal healing was also significantly more frequent in infliximab recipients. At week 8, approximately 30% of placebo-treated compared with 60% of infliximab-treated patients had complete mucosal healing or only mild lesions, and this difference remained significant at week 30 in both ACT-1 and ACT-2, and at 54 weeks in ACT-1. A recent Cochrane analysis concluded that there is level 1 evidence to support the efficacy of infliximab in UC based mainly on the ACT-1 and ACT-2 trial results (Lawson et al. 2006). The relative risk versus placebo to be in clinical remission with intravenous infliximab 5 mg/kg at weeks 0, 2, and 6 was 3.2 [95% confidence interval (CI) 2.18, 4.76]. Furthermore, infliximab produced clear steroid-sparing effects. In ACT-1, the median prednisolone dose decreased from 20 mg at baseline to 8.5 mg at week 54. Despite the steroid-sparing potential, however, only 21% of patients were in clinical remission and off steroids at 1 year. This indicates that one in three patients in remission still had some degree of steroid therapy, but the figures compare well with data observed in Crohn’s disease maintenance trials with anti-TNF agents (Hanauer et al. 2002). As in Crohn’s disease, the 10 mg/kg dose appeared to offer no additional clinical benefit over the 5 mg/kg dose of infliximab. Evidence from active comparator trials Recently, two small, open-label, randomized trials were initiated to explore the efficacy of infliximab compared with oral corticosteroids in patients with active disease not failing steroids. A first study enrolled 20 patients with moderate to severe (Mayo score ≥6) disease to receive infliximab 5 mg/kg intravenously at 0, 2, and 6 weeks and every 8 weeks thereafter, or corticosteroids 0.7–1 mg/kg for 1 week followed by gradual tapering (Armuzzi et al. 2004). Preliminary results showed that all patients (10/10) in both groups achieved clinical remission. After a median of 10 months’ follow-up, 9/10 of the infliximab group and 8/10 of those on corticosteroids were still in clinical remission. Patients who relapsed were successfully treated either with infliximab at shorter intervals of 6 to 4 weeks (initial infliximab group) or with infliximab at 0, 2, and 6 weeks (steroid group). Ochsenkühn et al. (2003) also reported preliminary data from an open-label, randomized trial comparing intravenous infliximab 5 mg/kg given at week 0, 2, and 6 (n=6) with high-dose prednisolone 1.5 mg/kg (n=7) for inducing remission in active UC not failing steroids. Clinical response was achieved in 5/6 of the infliximab- and in 6/7 steroid-treated patients. Infliximab in fulminant colitis An initial report by Chey et al. (2001) showed an extremely high efficacy in 16 patients with severe disease. In seven of these patients infliximab was used as a rescue therapy to avoid colectomy. After a single infliximab 5 mg/kg infusion, 88% of patients responded with a marked clinical and endoscopic improvement. Successful steroid tapering was possible in most 157