| Indication |
Reducing signs and symptoms of Crohn's disease and treatment of moderately to severely active rheumatoid arthritis (RA). |
| Mechanism of action |
Certolizumab pegol binds to free and membrane-bound human TNF? with a KD of 90pM and neutralizes its activity. Extent of neutralization is also dose-dependent. It also inhibited the release of lipopolysaccharide-induced IL-1? from monocytes. TNF? is a key pro-inflammatory cytokine with a central role in inflammatory processes in which elevated levels have been observed in patients with RA and Crohn's. Certolizumab pegol selectively neutralizes TNF? (IC90 of 4 ng/mL for inhibition of human TNF? in the in vitro L929 murine fibrosarcoma cytotoxicity assay). It does not bind to TNF-?. As certolizumab is only a Fab' fragment and thus missing the Fc region, it does not fix complement or cause antibody-dependent cell-mediated cytotoxicity. Furthermore, apoptosis of monocytes or lymphocytes, or neutrophil degranulation have not been observed in vitro. |
| Absorption |
There is a linear relationship between dose administered and Cmax and AUC. A mean Cmax of approximately 43 to 49 mcg/mL occurred at Week 5 during the initial loading dose period using the recommended dose regimen for the treatment of patients with rheumatoid arthritis (400 mg sc at Weeks 0, 2 and 4 followed by 200 mg every other week).
Tmax, SubQ dose = 54 - 171 hours;
Bioavailability, SubQ dose = 80% (range of 76% - 88%) |
| Protein binding |
Not Available |
| Biotransformation |
Metabolism has not been studied in humans. |
| Route of elimination |
The route of elimination of certolizumab pegol has not been studied in human subjects. Studies in animals indicate that the major route of elimination of the PEG component is via urinary excretion. |
| Toxicity |
The most common adverse reactions (incidence >=7% and higher than placebo): upper respiratory tract infection, rash, and urinary tract infection. |
| Affected organisms |
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