Jean-Frédéric Colombel1, William J Sandborn2, Matthieu Allez3, Jean-Louis Dupas4, Olivier Dewit5, Geert D'Haens6, Yoram Bouhnik7, Gerald Parker8, Bosny Pierre-Louis8, Xavier Hébuterne9. 1. Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: jean-frederic.colombel@mssm.edu. 2. University of California San Diego, La Jolla, California. 3. Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France. 4. Centre Hospitalier Universitaire Amiens, Amiens, France. 5. Université Catholique de Louvain Saint Luc, Brussels, Belgium. 6. Academic Medical Centre, Amsterdam, The Netherlands. 7. Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France. 8. UCB Pharma, Raleigh, North Carolina. 9. Centre Hospitalier Universitaire Nice, Nice, France; University of Nice Sophia Antipolis, Nice, France.
Abstract
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.
BACKGROUND & AIMS: Monitoring plasma concentrations of anti-tumornecrosis 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-tumornecrosis factor agents and therapeutic drug monitoring to optimize treatment. Clinicaltrials.gov Number, NCT00297648.
Authors: Charles W Randall; John A Vizuete; Nicholas Martinez; John J Alvarez; Karthik V Garapati; Mazyar Malakouti; Carlo M Taboada Journal: Therap Adv Gastroenterol Date: 2015-05 Impact factor: 4.409
Authors: Konstantinos Papamichael; Adam S Cheifetz; Gil Y Melmed; Peter M Irving; Niels Vande Casteele; Patricia L Kozuch; Laura E Raffals; Leonard Baidoo; Brian Bressler; Shane M Devlin; Jennifer Jones; Gilaad G Kaplan; Miles P Sparrow; Fernando S Velayos; Thomas Ullman; Corey A Siegel Journal: Clin Gastroenterol Hepatol Date: 2019-03-27 Impact factor: 11.382