Incidence and clinical significance of immunogenicity to infliximab in Crohn's disease: A critical systematic review

Abstract

Background: Infliximab (IFX) is a chimeric (mouse/human) anti-TNF-alpha monoclonal antibody approved for the treatment of refractory luminal and fistulizing Crohn's disease (CD). It is a source of potential immunogenicity for humans, with the occurrence of anti-infliximab antibodies (ATIs), which are thought to interfere with the pharmacodynamics and/or pharmacokinetics of the compound. It remains unclear whether ATIs have any clinical importance for drug efficacy or safety. We review studies specifically evaluating the incidence of ATIs in CD and their impact on the efficacy and safety of IFX. Methods: A systematic review was undertaken by electronic searches of the PubMed and SCOPUS databases from earliest records to October 2008, as well as reference lists of all relevant articles and relevant abstracts from meetings. Results: The biological and clinical mechanisms of ATI development are poorly understood. The incidence of ATIs in vivo depends on multiple analytical and clinical factors, both patient- and treatment-related. The presence of ATIs is weakly and variably associated with clinical response or infusion reactions, but not with reactions relevant to clinical decision-making. Enormous variation in the methods of reporting ATIs and immunogenicity of IFX make almost any interpretation possible from different studies, but few have clinical relevance. Conclusions: There is no clear evidence that ATIs have an impact on efficacy or safety, nor a need to measure or prevent them in clinical practice. Circulating drug concentration may be a more relevant measure of immunogenicity. Copyright © 2009 Crohn's & Colitis Foundation of America, Inc.