Certolizumab pegol: a PEGylated anti-tumour necrosis factor alpha biological agent

Abstract

Tumour necrosis factor (TNF)alpha is a proinflammatory cytokine involved in systemic inflammation that mediates chronic inflammatory diseases such as rheumatoid arthritis (RA), Crohn's disease (CD) and psoriasis. Recognition of TNF alpha as a primary mediator of inflammatory disease has driven the development of monoclonal antibodies (mAbs) against TNF alpha as potential novel therapies for these disorders. Certolizumab pegol is a novel, polyethylene glycol (PEG)-conjugated, humanised, antigen-binding fragment (Fab') of an anti-TNF alpha mAb that does not mediate apoptosis or neutrophil degranulation. Preclinical studies have shown excellent bioavailability, with preferential distribution and retention in inflamed tissue, which could be due to the low diffusion rate of PEGylated molecules and/or the lack of an Fc, which prevents FcRn-mediated transport. Pharmacokinetics are linear and predictable. Certolizumab pegol is a potentially valuable new treatment option for several inflammatory diseases. It has shown promising efficacy and tolerability results in Phase II and III trials for RA, CD and psoriasis.