title: Association between plasma concentrations of certolizumab pegol and endoscopic outcomes of patients with Crohn's disease.
abstract: OBJECTIVE
  Monitoring plasma concentrations of anti-tumor necrosis factor agents could optimize treatment of patients with Crohn's Disease (CD). In a post hoc analysis of data from a clinical trial, we compared the relationship between plasma concentrations of certolizumab pegol (CZP) and endoscopic and clinical responses and remission with CZP therapy in patients with moderate to severe ileocolonic CD.
  
  
  METHODS
  We analyzed data from the Endoscopic Mucosal Improvement in Patients with Active CD Treated with CZP trial, from 89 adult patients with active endoscopic CD (ulceration in ≥ 2 intestinal segments and CD Endoscopic Index of Severity [CDEIS] scores of ≥ 8 points). Patients received subcutaneous CZP (400 mg) at weeks 0, 2, and 4 and then every 4 weeks until week 52. Endoscopic evaluations were performed at weeks 0, 10, and 54. Blood samples were collected to measure CZP plasma concentrations at weeks 8 and 54. CZP quartiles at weeks 8 (n = 80) and 54 (n = 45) were correlated with endoscopic response (>5-point decrease in CDEIS from baseline) and remission (CDEIS, <6) at weeks 10 and 54, respectively.
  
  
  RESULTS
  Higher concentrations of CZP at week 8 were associated with endoscopic response (P = .0016) and remission (P = .0302) at week 10 (n = 45). At week 54, the rates of endoscopic remission correlated with plasma concentrations of CZP (P = .0206). There was a significant inverse relationship between plasma concentrations of CZP and baseline levels of C-reactive protein and body weight (P = .0014 and P = .0373, respectively).
  
  
  CONCLUSIONS
  Endoscopic response and remission are associated with higher plasma concentrations of CZP in patients with moderate to severe ileocolonic CD. These results support the need to consider the pharmacokinetics of anti-tumor necrosis factor agents and therapeutic drug monitoring to optimize treatment. Clinicaltrials.gov Number, NCT00297648.
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: jean-frederic.colombel@mssm.edu.
authors.forename: Jean-Frédéric
authors.initials: JF
authors.lastname: Colombel
authors.affiliation: University of California San Diego, La Jolla, California.
authors.forename: William J
authors.initials: WJ
authors.lastname: Sandborn
authors.affiliation: Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Allez
authors.affiliation: Centre Hospitalier Universitaire Amiens, Amiens, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Dupas
authors.affiliation: Université Catholique de Louvain Saint Luc, Brussels, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: Dewit
authors.affiliation: Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Geert
authors.initials: G
authors.lastname: D'Haens
authors.affiliation: Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Bouhnik
authors.affiliation: UCB Pharma, Raleigh, North Carolina.
authors.forename: Gerald
authors.initials: G
authors.lastname: Parker
authors.affiliation: UCB Pharma, Raleigh, North Carolina.
authors.forename: Bosny
authors.initials: B
authors.lastname: Pierre-Louis
authors.affiliation: Centre Hospitalier Universitaire Nice, Nice, France; University of Nice Sophia Antipolis, Nice, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Hébuterne
mesh_terms: D000293:Adolescent; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000068582:Certolizumab Pegol; D003113:Colonoscopy; D003424:Crohn Disease / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000097:blood* / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D008297:Male; D010949:Plasma / Q000737:chemistry; D011092:Polyethylene Glycols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007140:Immunoglobulin Fab Fragments; D007166:Immunosuppressive Agents; D011092:Polyethylene Glycols; D000068582:Certolizumab Pegol
keywords: CDAI; MUSIC Trial; PK Study; TNF Inhibitor