Certolizumab pegol for the treatment of Crohn's disease

Abstract

In this article we provide a contemporary overview of available clinical data on certolizumab pegol, a pegylated anti-tumor necrosis factor (TNF) alpha agent that comprises a uniquely small protein, and its emerging role as a therapy for Crohn's disease (CD). The results from a comprehensive clinical trial program suggest that certolizumab pegol offers rapid and sustained remission of moderate to severe CD. Certolizumab pegol is an effective and well-tolerated therapy both in patients who have already received biologics and in patients who are anti-TNF naïve. Benefits of therapy include a stable dosing regimen, which allows for rapid induction of a clinical response followed by long-term maintenance of response and remission under one fixed dose. Treatment with certolizumab pegol has been shown to improve function and quality of life in patients with CD, and insights into the potential mechanisms by which certolizumab pegol effects a response in CD suggest that this agent may have the potential to slow or even modify disease progression. Early therapy is particularly effective and could help control CD progression and lessen the burden of disease on patients.

Keywords: Anti-TNF; Crohn’s disease; TNFα inhibitors; certolizumab pegol.

Figures

Figure 1.

Comparative structures of the anti-TNF agents infliximab, adalimumab and certolizumab pegol. Infliximab is a chimeric IgG1 monoclonal antibody, the Fc’ portion of which is human. Adalimumab is a human IgG1 monoclonal antibody. Certolizumab pegol is a human monoclonal antibody Fab′ conjugated with polyethylene glycol (PEG), an inert 40-kDa macromolecule used to enhance the pharmacokinetic properties of biologics. Adapted with permission from Adis Data Information BV [Bourne et al. 2008, 22(5): 331–337], copyright © 2008.

Figure 2.

(A) Response over time in patients in the intention-to-treat population who had responded to induction therapy at week 6 in PRECiSE 2. The percentage of patients with a response in the certolizumab pegol group was greater than in the placebo group in both the intention-to-treat population and in the high C-reactive protein (CRP) group (p < 0.001). Reprinted with permission from the Massachusetts Medical Society [Schreiber et al. 2007], copyright © 2007. (B) Median Crohn’s Disease Activity Index (CDAI) scores (last observation carried forward) over time in the intention-to-treat population in PRECiSE 2. Median CDAI remission scores were significantly lower in the certolizumab pegol group than in the placebo group at week 16 (p = 0.03), week 20 (p = 0.02), week 24 (p = 0.008) and week 26 (p < 0.001). Reprinted with permission from the Massachusetts Medical Society [Schreiber et al. 2007], copyright © 2007.

Figure 3.

Improvement in various health-related quality of life measures with certolizumab pegol in PRECiSE 2. PCS, physical component summary; MCS, mental component summary; VAS, visual analog scale; IBDQ, inflammatory bowel disease questionnaire. *p < 0.05 (logistic regression). †p < 0.001 (logistic regression). Error bars represent the 95% confidence interval. Reprinted with permission from Macmillan Publishers Ltd [Feagan et al. 2009b, 104(8)], copyright © 2009.

Figure 4.

Improvement in work productivity with certolizumab pegol in PRECiSE 2. Mean changes in Work Productivity and Activities Index in Crohn’s disease (WPAI:CD) scores and 95% confidence interval (within-treatment) (A) at week 26 from week 6 (maintenance phase) and (B) at week 26 from baseline (induction and maintenance). *p < 0.05. **p < 0.001; comparisons within treatment groups for week 6 versus week 26 (a) and week 0 versus week 26 (b) are by paired t-test (change significantly different from 0). †p < 0.05, ††p < 0.01, †††p < 0.001; comparisons between the two treatment arms are by Student’s t-test. A larger negative change means greater improvement for each parameter. Reprinted with permission from Blackwell Publishing Ltd [Feagan et al. 2010, pp. 1276–1285], copyright © 2010.