Number of records Full papers Abstracts 0 1 1 0 1 1 0 Table 1 | Evidence base included in the review Category Initial search records excluded records included Additional studies identified Total records included Level 1 clinical evidence (systematic review, meta analysis) Level 2 clinical evidence (RCT) Level ≥3 clinical evidence Economic evidence 268 243 25 32 57 1 5 20 0 Infliximab | place in therapy review Scope, aims, and objectives Despite the therapeutic efficacy of the biologic agent infliximab (Remicade®) in Crohn’s disease, the development of agents specifically interacting with an immune pathway has not led to registered novel therapeutics in ulcerative colitis (UC). Recently more biologic agents have entered development programs in this indication but contrary to the situation in Crohn’s disease, many of these programs have originally been driven by interest from investigators involved in patient care and not by the pharmaceutical industry. Several reasons may underlie this discrepancy in “market interest” between Crohn’s disease and UC. First, the immunopathogenesis of UC is ill-defined and this hinders the selection of a clear target pathway. The lack of paradigm about cytokines driving the inflammatory reaction in UC prevents extrapolation to other diseases such as rheumatoid arthritis, spondyloarthropathy, or psoriasis, as is the case for Crohn’s disease. Finally, colectomy with ileal pouch anastomosis is viewed by many as a good solution for refractory UC even with all the possible long-term inconveniences associated with this procedure. Although the pathogenesis of UC is incompletely understood, several lines of evidence justify the development of antitumor necrosis factor (anti-TNF) agents in the medical management of UC. Until 2 years ago, most of the data had originated from uncontrolled studies, but three large, placebo- controlled trials have recently demonstrated that for moderate to severe UC and for fulminant steroid-refractory UC, the anti- TNF agent infliximab has clinical efficacy. This review will discuss the scientific rationale for using anti-TNF agents in UC and will address the current evidence supporting a role for infliximab in inducing and maintaining clinical improvement in active UC. Methods English language literature searches were conducted in the following databases, searching from the beginning of the database to date unless otherwise stated. The search strategy was “infliximab AND ulcerative colitis” unless otherwise stated (Table 1): • PubMed, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi • Web of Science, http://scientific.thomson.com/products/wos • Cochrane Database of Systematic http://www.cochrane.org/index0.htm Reviews (CDSR), Disease overview Inflammatory bowel diseases (IBD) are chronically relapsing intestinal inflammatory conditions with a typical onset in young adulthood and with an unpredictable disease course that may lead to debilitating complications. Crohn’s disease and UC are the two main phenotypes of IBD. These chronic immune- mediated disorders are characterized by abdominal symptoms 152 For definitions of levels of evidence, see Editorial Information on inside back cover or on Core Evidence website. RCT, randomized controlled trial. (diarrhea, abdominal pain, rectal bleeding) and systemic manifestations (arthralgia, fatigue, dermatologic and biliary complications). The most pertinent difference between the two illnesses is the disease location. Crohn’s disease typically occurs in the terminal ileum (terminal enteritis) and right-sided colon. However, lesions can appear anywhere in the gut and the disease frequently affects different parts of the intestine with skip areas of uninvolved mucosa (regional enteritis). UC, on the other hand, most often involves the rectum and extends over a variable distance in the colon. Two-thirds of patients have only left-sided colonic disease with sparing of the right colon. Also, Crohn’s disease is a transmural disease leading to fistulas and intestinal strictures, whereas UC only affects the colonic mucosa and submucosa. While UC can present at any age, patients are often diagnosed in young adulthood, which means that this disease is associated with a high psychologic and socioeconomic burden. The diagnosis is based on the clinical presentation, on findings at colonoscopy, and on histologic findings in mucosal biopsies. The course of UC is notably unpredictable at diagnosis. Some patients have smoldering disease with few symptoms and occasional flares, but others have signs of severe systemic inflammation and debilitating diarrhea with abdominal cramps, necessitating aggressive medical management. Fifteen to twenty percent of patients will develop fulminant colitis necessitating hospitalization and intravenous therapy during the course of their disease. Complications include toxic megacolon, profuse colonic bleeding, and colorectal cancer. UC is relatively infrequent with an estimated incidence of five per 100 000 in the US, Canada, Australia, South Africa, and northwestern Europe. Latin and South America, southern Europe, and the rest of the world appear to have a much lower incidence. However, since UC is a lifetime illness, peak prevalences of one in 500 have been reported. At present most patients need to be treated long term (several decades). © 2007 Core Medical Publishing Limited