decision-making and timely colectomy can prevent surgical complications and save patient lives, and should always be considered. Unmet needs The main unmet medical needs in UC are in patients with moderate to severe disease failing 5-aminosalicylates and more importantly corticosteroids, and also patients with corticosteroid- dependent disease, who are at high risk of major side effects from steroid therapy. In fulminant colitis, colectomy can be prevented in the short term by intravenous corticosteroids, and by cyclosporine in steroid-refractory patients, but long-term disease control and salvage from colectomy is substantially reduced despite the association of antimetabolite therapy. More specifically, in patients failing adequate therapy with azathioprine or 6-mercaptopurine, steroids and cyclosporine are of limited value since they offer no long-term perspective. Also surgical proctocolectomy, although a good solution for patients with intractable disease or neoplasia, has several limitations including pouchitis, postoperative obstruction, frequent stools, and reduced female fecundity. Complications occur only in a small proportion of patients, but cannot be predicted prior to the procedure. Therapeutic potential can therefore be expected from therapies that meet all or most of the following aims: • Induction and maintenance of symptomatic remission in a high proportion of patients • Sparing of corticosteroids • Induction of endoscopic mucosal healing • Prevention of surgery and avoidance of surgical complications if colectomy is needed • Long-term, highly beneficial benefit-to-risk ratio, including the risk of colonic dysplasia. In an attempt to address these needs and utilize the role of TNF in UC pathogenesis, a number of anti-TNF agents have been investigated. CDP-571 is a humanized, anti-TNF, IgG4 antibody that has been evaluated in an open-label trial, and shows some improvement in clinical scores although the effect was short-lived (Evans et al. 1997). A total of 15 patients with mild to moderate, mostly left- sided disease were included. In these patients a significant reduction in the mean Powell-Tuck scores was observed as soon as 1 week after infusion of CDP-571 at 5 mg/kg, although the endoscopic scores did not improve. The development of CDP-571 has been halted. RDP58 has been rationally designed to block the translation of several cytokines such as TNF, IL-2, and IL-12. It is an interesting small molecule that inhibits the production of several cytokines Core Evidence 2007;2(3) Infliximab | place in therapy review including TNF at a posttranscriptional level and has been studied in patients with moderately active UC. In a randomized trial patients received placebo, or RDP58 100, 200, or 300 mg daily for 4 weeks (Travis et al. 2003). Both higher doses resulted in high clinical remission rates (72% and 70% vs 40% in placebo-treated patients). Also, histologic scores decreased more in RDP58- treated patients. In this trial the placebo remission rate of 40% was exceptionally high. Nevertheless, the drug appeared to be safe and is appealing due to its oral route of administration and its very low absorption. This low systemic bioavailability could have favorable implications for the side effect profile. Infliximab has been investigated in patients with UC, and forms the focus of this review. Clinical evidence for the use of infliximab in UC Infliximab in adult UC Open-label studies The first reports on the use of the chimeric, humanized, anti-TNF, IgG1 antibody infliximab in Crohn’s disease date back to 1995 and the compound has changed the treatment paradigm for this illness. In UC, infliximab has been evaluated initially in several open-label trials for refractory, moderate to severe disease. The open-label trial experience with infliximab treatment for moderately to severely active UC has generated conflicting results to say the least (Table 3). Differences in patient populations and the lack of strict diagnostic criteria at baseline only partially account for this discrepancy. Differences in clinical scores used to evaluate disease and in study endpoints (response vs remission) are also only part of the explanation. As suggested in several editorials, a strong placebo response for patients receiving an intravenous treatment with proven high efficacy in Crohn’s disease may have influenced the judgment of both patients and investigators (Rutgeerts 2002; Cohen 2003). A US, multicenter, open-label trial involving 27 patients (mostly outpatients despite 89% having severe disease) investigated one to three infusions of infliximab 5 mg/kg (Chey et al. 2001). Remission was observed in 44% of patients and another six patients (22%) had a partial response. The median time to response was 4 days and the median response duration 8 weeks. Most nonresponding patients underwent colectomy. Interestingly, steroid-refractory patients were less likely to respond than those responding but relapsing during steroid tapering (33% vs 83%). Subsequently, several papers describing open-label trial experience with infliximab were published. These trials have generated opposing data on putative efficacy but no important safety concerns have arisen. Bermejo et al. (2004) reported on the use of infliximab in seven patients with disease refractory to standard treatment. Of the six patients with steroid-dependent disease, five (83%) responded both clinically and endoscopically. Similarly, Kohn et al. (2002) reported on the success of infliximab treatment in 13 patients admitted to a Turin academic hospital. The retrospective analysis showed that clinical response was obtained in 77% of infliximab-treated patients. A similar high 155