Place in therapy review Infliximab: the evidence for its place in therapy in ulcerative colitis Gert Van Assche, Séverine Vermeire, Paul Rutgeerts Division of Gastroenterology, University of Leuven Hospitals, Herestraat 49, B-3000 Leuven, Belgium Abstract Introduction: Refractory ulcerative colitis has a high, unmet medical need for avoiding steroid dependency and avoiding colectomy. Controlled trials with biologic agents have recently been reported. Aims: We aimed to review the current evidence supporting the use of the monoclonal antitumor necrosis factor antibody, infliximab, in active ulcerative colitis and determine its current place in therapy. Evidence review: Although faced with initial conflicting data particularly in steroid-refractory patients, two large, placebo-controlled trials have shown that intravenous infliximab induces and maintains clinical improvement in a clinically significant proportion of patients when used with scheduled re-treatment. Infliximab also spares steroids and induces endoscopic remission in moderately ill patients. In fulminant colitis unresponsive to intravenous steroids, one placebo-controlled trial indicates that infliximab is able to prevent colectomy in this patient population. Evidence for cost effectiveness and avoidance of colectomy long term are still lacking. Place in therapy: Infliximab 5 mg/kg induction at 0, 2, and 6 weeks, and every 8 weeks thereafter should be considered in patients with moderately to severely active ulcerative colitis failing medical therapy. Steroid-dependent and steroid-refractory patients also qualify for infliximab therapy. Core Evidence. 2007;2(3):151–161. Key words: biologic agents, fulminant colitis, infliximab, mucosal healing, ulcerative colitis Core evidence place in therapy summary for infliximab in moderate to severe ulcerative colitis Outcome measure Patient-oriented evidence Improvement of symptoms Maintenance of clinical response Sparing of steroids Prevention of colectomy Improvement in quality of life Efficacy superior to steroids Disease-oriented evidence Endoscopic healing of mucosal lesions Induction of T-cell apoptosis Prevention of colonic dysplasia Economic evidence Cost effectiveness as an alternative to corticosteroid therapy Cost effectiveness as an alternative to calcineurin inhibitors or colectomy in fulminant colitis Evidence Clear Clear Clear Moderate Limited Limited Clear No evidence No evidence No evidence No evidence Implications Improved disease control Improved disease control long term Prevention of steroid-induced complications in corticodependent patients Substantial evidence on short-term efficacy; long-term data awaited Reduced hospitalizations No controlled comparative trials available; uncontrolled trials suggesting equivalence Biologic endpoint reflecting reduced colonic inflammation and increased mucosal repair Apoptosis induction as a mechanism of action for biologics has not been established in ulcerative colitis Mucosal healing is associated with a decreased risk of dysplasia, but no data are available for infliximab Long-term pharmacoeconomic studies missing Long-term colectomy avoidance data missing