Targeting nanomedicines in the treatment of Crohn's disease: focus on certolizumab pegol (CDP870).
A variety of targets for therapeutic intervention are based upon advances in understanding of the immunopathogenesis of Crohn's disease. Crohn's disease is initiated by an innate immune response, which eventuates in a T-cell driven process, characterized by a T-helper cell 1 type cytokine profile. Several new treatments now focus on suppressing T-cell differentiation or T-cell inflammation. Since inflammatory bowel disease (IBD) represents a state of dysregulated inflammation, drugs that augment the anti-inflammatory response have the potential to downregulate inflammation and thereby hopefully modify the disease. Tumour necrosis factor (TNF) is a major target of research and clinical investigation. TNF has proinflammatory effects in the intestinal mucosa and is a pivotal cytokine in the inflammatory cascade. Certolizumab pegol (CDP870) is a PEGylated, Fab' fragment of a humanized anti-TNF-alpha monoclonal antibody. PEGylation increases the half-life, reduces the requirement for frequent dosing, and possibly reduces antigenicity as well. Certolizumab has been shown in Phase III trials to achieve and maintain clinical response and remission in Crohn's disease patients. It improves the quality of life. Certolizumab pegol will be indicated for moderately to severely active Crohn's disease, but it is not yet licensed in Europe or the US. It is not possible to construct an algorithm for treatment, but when compared with infliximab the two principal advantages are likely to be lower immunogenicity (as shown by anti-drug antibodies, absence of infusion reactions, and low rate of antinuclear antibodies), and a subcutaneous route of administration. These two factors may be sufficient to promote it up the pecking order of anti-TNF agents.
Dinesen
Lotte
L
Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK.
Travis
Simon
S
D061067:Antibodies, Monoclonal, Humanized; D000068582:Certolizumab Pegol; D002986:Clinical Trials as Topic / Q000639:trends; D003424:Crohn Disease / Q000188:drug therapy*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage* / Q000737:chemistry*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000737:chemistry; D050997:Nanomedicine / Q000639:trends*; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry*
D061067:Antibodies, Monoclonal, Humanized; D004337:Drug Carriers; D007140:Immunoglobulin Fab Fragments; D007166:Immunosuppressive Agents; D011092:Polyethylene Glycols; D000068582:Certolizumab Pegol