Comprehensive review: antitumor necrosis factor agents in inflammatory bowel disease and factors implicated in...

Antitumor necrosis factor α (anti-TNF) agents have dramatically influenced management of refractory inflammatory bowel disease (IBD). However, not all patients respond to treatment and some lose response or become intolerant over time. Immunogenicity, a well established phenomenon with anti-TNF agents, may have important clinical implications in patients with IBD. A comprehensive review of available evidence demonstrating how drug concentrations, immunogenicity, and other factors influence outcomes with anti-TNF agents was performed. PubMed, EMBASE, Biosis, Dialog, and Conference Papers Index were searched from 1 January 1995 to 7 April 2012 to identify clinical trials in adult and pediatric patients with IBD treated with anti-TNF agents for Crohn's disease or ulcerative colitis. Data on serum drug levels and immunogenicity and their relationship with clinical efficacy and safety outcomes were extracted and examined. Serum infliximab concentrations correlated with clinical efficacy and treatment outcomes in patients with IBD; this relationship is less well characterized with adalimumab and certolizumab pegol concentrations. In multiple studies, the presence and level of antibodies to infliximab correlated with loss of clinical efficacy and increased risk of infusion reactions. The incidence and clinical impact of antibody formation with adalimumab or certolizumab in IBD is becoming evident as more data become available. Current, enzyme-linked immunosorbent assay based anti-TNF antibody assays are suboptimal in that results are often inconclusive and comparisons between agents cannot be made. Measurement of anti-TNF agent drug concentrations and assessment of immunogenicity has the potential to positively impact clinical decision making during anti-TNF therapy for IBD. As assays are optimized, it is expected that the clinical impact of these determinations will be better characterized.