TY - JOUR
T1 - Association between plasma concentrations of certolizumab pegol and endoscopic outcomes of patients with Crohn's disease
AU - Colombel, Jean Frédéric
AU - Sandborn, William J.
AU - Allez, Matthieu
AU - Dupas, Jean Louis
AU - Dewit, Olivier
AU - D'Haens, Geert
AU - Bouhnik, Yoram
AU - Parker, Gerald
AU - Pierre-Louis, Bosny
AU - Hébuterne, Xavier
N1 - Funding Information:
Funding The MUSIC study ( NCT00297648 ) was funded by UCB Pharma .
Funding Information:
Editorial assistance was provided by a contract medical writer (Ann P. Tighe, PhD, of PPSI [a PAREXEL company]), funded by UCB Pharma and by Matladi Ndlovu, PhD, of UCB Pharma.
PY - 2014/3
Y1 - 2014/3
N2 - Background & Aims: 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.
AB - Background & Aims: 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.
KW - CDAI
KW - MUSIC Trial
KW - PK Study
KW - TNF Inhibitor
UR - http://www.scopus.com/inward/record.url?scp=84893898345&partnerID=8YFLogxK
U2 - 10.1016/j.cgh.2013.10.025
DO - 10.1016/j.cgh.2013.10.025
M3 - Article
C2 - 24184736
AN - SCOPUS:84893898345
SN - 1542-3565
VL - 12
SP - 423-431.e1
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 3
ER -