PEGylation of
biological proteins, defined as the covalent conjugation of
proteins with
polyethylene glycol (PEG), leads to a number of
biopharmaceutical improvements, including increased half-life, increased solubility and reduced aggregation, and reduced immunogenicity. Since their introduction in 1990, PEGylated
proteins have significantly improved the management of various
chronic diseases, including
rheumatoid arthritis (RA) and
Crohn's disease.
Certolizumab pegol is the only PEGylated anti-tumour
necrosis factor (TNF)-α agent. It is a PEGylated, humanised,
antigen-binding fragment of an anti-TNF
monoclonal antibody. Unlike other anti-TNF agents, it has no crystallisable
fragment (Fc) domain. Because of its novel structure,
certolizumab pegol may have a different mechanism of action to the other anti-TNF agents, and also has different pharmacodynamic properties, which could possibly translate to a different safety profile. Pharmacodynamic studies have shown that
certolizumab pegol binds to TNF with a higher affinity than
adalimumab and
infliximab.
Certolizumab pegol is also more potent at neutralising soluble TNF-mediated signalling than
adalimumab and
infliximab, and has similar or lesser potency to
etanercept.
Certolizumab pegol does not cause detrimental in vitro effects such as degranulation, loss of cell integrity, apoptosis,
complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity.
Certolizumab pegol may also penetrate more effectively into inflamed arthritic tissue than other anti-TNF agents, and is not actively transported across the placenta during pregnancy. Pharmacokinetic studies in healthy volunteers demonstrated that single intravenous and subcutaneous doses of
certolizumab pegol had predictable pharmacokinetics. The pharmacokinetics of
certolizumab pegol in patients with RA and
Crohn's disease were consistent with pharmacokinetics in healthy volunteers.