Infliximab and ulcerative colitis

Abstract

Tumour necrosis factor (TNF)-alpha is an inflammatory cytokine that plays a main role in the inflammatory process underlying inflammatory bowel disease (IBD). Despite the fact that the cytokine profiles associated with ulcerative colitis (UC) and Crohn's disease (CD) are classically considered different (a Th2 pattern in UC and a Th1 pattern in CD), there are several evidences in vitro and in vivo that TNF-alpha has an important role in UC. For this reason, infliximab, the chimeric monoclonal antibody to TNF-alpha, has been evaluated in the therapy of UC. The drug has been evaluated in different clinical settings both in adults and in children: in moderate-severe steroid-dependent UC, in severe refractory UC as rescue therapy, in active non-steroid-refractory UC, in resistant pouchitis and in maintenance of moderate-severe UC responsive to infliximab. On the basis of the randomised controlled trials (RCTs), it is possible to draw the following conclusions for adults: infliximab seems active in severe steroid-refractory UC, allowing colectomy to be spared even if further controlled trials are needed with a larger sample of patients adopting strict and well-defined inclusion criteria. The drug seems active in inducing remission after 8 weeks in steroid-refractory patients, in patients taking steroids (even if it is not clear at which dosage of steroid dependence the drug is more active) and also in patients failing aminosalicylates therapy. The long-term response of infliximab in comparison to placebo in these subgroups of patients is not clinically impressive even if it is statistically significant. Further trials are warranted in order to establish the role of infliximab in steroid-dependent UC (defined with clear criteria), in maintaining remission after severe UC, in non-steroid-dependent moderate-severe UC and in refractory pouchitis. For children it is not possible to draw the same conclusions, due to a lack of RCTs, despite the encouraging data coming from open studies, mainly in steroid-refractory UC.