Certolizumab

Certolizumab pegol, a tumor necrosis factor α(TNF-α) blocker, was launched for the treatment of moderate-to-severe Crohn’s disease. It is specifically indicated for reducing signs and symptoms and maintaining clinical response in adult patients who have had an inadequate response to conventional therapy. Certolizumab pegol is the third anti-TNF-α biologic to be marketed for this indication behind infliximab (Remicade) and adalimumab (Humira). Certolizumab pegol is a recombinant, humanized antibody Fab’ fragment linked to approximately 40 kDa polyethylene glycol (PEG). The Fab’ fragment is composed of a light chain with 214 amino acids and a heavy chain with 229 amino acids. It is manufactured in E.coli and is subsequently subjected to purification and conjugation to PEG, to generate certolizumab pegol. The addition of PEG moiety significantly enhances the plasma half-life of the antibody, allowing for less frequent dosing. Certolizumab pegol neutralizes both soluble and membrane-associated forms of human TNF-a. It binds to human TNF-a with slightly higher affinity (KD 0.09 nM) than infliximab (KD 0.23 nM) and adalimumab (KD 0.16 nM). In addition, in cellular assays, certolizumab pegol is more potent in preventing TNF-a-induced killing of L929 fibroblasts than infliximab and adalimumab (IC50 0.35 ng/mL versus 5 and 6 ng/mL, 592 Shridhar Hegde and Michelle Schmidt respectively).

Treatment of rheumatoid arthritis and inflammatory bowel disease.

The most common adverse reactions with certolizumab were upper respiratory infections (20%), urinary tract infections (7%), and anthralgias (6%). TNF-a blockers as a class have been linked to increased risk of opportunistic infections and malignancy. Tuberculosis, invasive fungal infections, and other serious infections have occurred in patients receiving certolizumab pegol, and the drug label contains a black-box warning of the risk.