Certolizumab pegol for the treatment of Crohn's disease.

Abstract

BACKGROUND:

Certolizumab pegol is a pegylated humanized Fab' fragment that binds tumor necrosis factor alpha.

METHODS:

In a randomized, double-blind, placebo-controlled trial, we evaluated the efficacy of certolizumab pegol in 662 adults with moderate-to-severe Crohn's disease. Patients were stratified according to baseline levels of C-reactive protein (CRP) and were randomly assigned to receive either 400 mg of certolizumab pegol or placebo subcutaneously at weeks 0, 2, and 4 and then every 4 weeks. Primary end points were the induction of a response at week 6 and a response at both weeks 6 and 26.

RESULTS:

Among patients with a baseline CRP level of at least 10 mg per liter, 37% of patients in the certolizumab group had a response at week 6, as compared with 26% in the placebo group (P=0.04). At both weeks 6 and 26, the corresponding values were 22% and 12%, respectively (P=0.05). In the overall population, response rates at week 6 were 35% in the certolizumab group and 27% in the placebo group (P=0.02); at both weeks 6 and 26, the response rates were 23% and 16%, respectively (P=0.02). At weeks 6 and 26, the rates of remission in the two groups did not differ significantly (P=0.17). Serious adverse events were reported in 10% of patients in the certolizumab group and 7% of those in the placebo group; serious infections were reported in 2% and less than 1%, respectively. In the certolizumab group, antibodies to the drug developed in 8% of patients, and antinuclear antibodies developed in 2%.

CONCLUSIONS:

In patients with moderate-to-severe Crohn's disease, induction and maintenance therapy with certolizumab pegol was associated with a modest improvement in response rates, as compared with placebo, but with no significant improvement in remission rates. (ClinicalTrials.gov number, NCT00152490 [ClinicalTrials.gov].).

• Authors: William J Sandborn, Brian G Feagan, Simeon Stoinov, Pieter J Honiball, Paul Rutgeerts, David Mason, Ralph Bloomfield, Stefan Schreiber, PRECISE 1 Study Investigators
• Journal: The New England journal of medicine (N Engl J Med) Vol. 357 Issue 3 Pg. 228-38 (Jul 19 2007) ISSN: 1533-4406 [Electronic] United States
• PMID: 17634458 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2007 Massachusetts Medical Society.

Chemical References

• Anti-Inflammatory Agents
• Antibodies
• Antibodies, Antinuclear
• Antibodies, Monoclonal, Humanized
• Immunoglobulin Fab Fragments
• Immunosuppressive Agents
• Tumor Necrosis Factor-alpha
• Polyethylene Glycols
• C-Reactive Protein
• Certolizumab Pegol

Topics

• Adolescent
• Adult
• Aged
• Anti-Inflammatory Agents (therapeutic use)
• Antibodies
• Antibodies, Antinuclear
• Antibodies, Monoclonal, Humanized
• C-Reactive Protein (analysis)
• Certolizumab Pegol
• Crohn Disease (classification, drug therapy, immunology)
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Humans
• Immunoglobulin Fab Fragments (adverse effects, immunology, therapeutic use)
• Immunosuppressive Agents (therapeutic use)
• Injections, Subcutaneous
• Male
• Middle Aged
• Polyethylene Glycols (adverse effects, therapeutic use)
• Remission Induction
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)