Certolizumab pegol for the treatment of Crohn's disease

N Engl J Med. 2007 Jul 19;357(3):228-38. doi: 10.1056/NEJMoa067594.

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].).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • 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

Associated data

  • ClinicalTrials.gov/NCT00152490