Monitoring a combination of calprotectin ...
Document type :
Article dans une revue scientifique: Article original
PMID :
Permalink :
Title :
Monitoring a combination of calprotectin and infliximab identifies patients with mucosal healing of crohn''s disease
Author(s) :
Dreesen, Erwin [Auteur]
Baert, Filip [Auteur]
Laharie, David [Auteur]
Bossuyt, Peter [Auteur]
Bouhnik, Yoram [Auteur]
Buisson, Anthony [Auteur]
Lambrecht, Guy [Auteur]
Louis, Edouard [Auteur]
Oldenburg, Bas [Auteur]
Pariente, Benjamin [Auteur]
Pierik, Marieke [Auteur]
Van Der Woude, C. Janneke [Auteur]
D''haens, Geert [Auteur]
Vermeire, Severine [Auteur]
Gils, Ann [Auteur]
Baert, Filip [Auteur]
Laharie, David [Auteur]
Bossuyt, Peter [Auteur]
Bouhnik, Yoram [Auteur]
Buisson, Anthony [Auteur]
Lambrecht, Guy [Auteur]
Louis, Edouard [Auteur]
Oldenburg, Bas [Auteur]
Pariente, Benjamin [Auteur]
Pierik, Marieke [Auteur]
Van Der Woude, C. Janneke [Auteur]
D''haens, Geert [Auteur]
Vermeire, Severine [Auteur]
Gils, Ann [Auteur]
Journal title :
Clinical gastroenterology and hepatology . the official clinical practice journal of the American Gastroenterological Association
Abbreviated title :
Clin. Gastroenterol. Hepatol.
Publication date :
2019-05-22
ISSN :
1542-7714
English keyword(s) :
Pharmacokinetics
Immunogenicity
Endoscopic Healing
Therapeutic Drug Monitoring
Immunogenicity
Endoscopic Healing
Therapeutic Drug Monitoring
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
In the TAILORIX trial, no benefit could be shown by infliximab dose escalation based on pharmacokinetic (infliximab serum concentrations) and pharmacodynamic (biomarkers and symptoms) monitoring compared with dose escalation ...
Show more >In the TAILORIX trial, no benefit could be shown by infliximab dose escalation based on pharmacokinetic (infliximab serum concentrations) and pharmacodynamic (biomarkers and symptoms) monitoring compared with dose escalation based on symptoms alone in patients with Crohn's disease (CD). We investigated whether integration of pharmacokinetic and pharmacodynamic monitoring can be used to evaluate responses to infliximab induction and maintenance therapy, based on findings from endoscopy. We performed a post hoc analysis of patients with CD included in a trial to test the effects of infliximab dose escalation, based on biomarkers and serum concentrations of infliximab, on symptoms (the Study Investigating Tailored Treatment With Infliximab for Active Crohn's Disease trial; n = 122). We analyzed data from this study to determine whether concentrations of biomarkers and serum concentrations of infliximab were associated with endoscopic outcomes (n = 116). The primary end points were endoscopic response (CD endoscopic index of severity decrease ≥50% from baseline), endoscopic remission (CD endoscopic index of severity, <3), and absence of ulcers at weeks 12 and 54 of infliximab treatment. Infliximab trough concentrations greater than 23.1 mg/L at week 2 and greater than 10.0 mg/L at week 6 were associated with endoscopic remission at week 12 (positive predictive values, 72% and 76%; negative predictive values, 65% and 59%, respectively). During maintenance therapy, we found evidence for an exposure-response relationship only after dose escalation; trough concentrations greater than 10.6 mg/L were associated with the absence of ulcers at week 54 (positive predictive value, 49%; negative predictive value, 92%). Low fecal concentrations of calprotectin during therapy were associated with endoscopic response and remission (P < .05). Dose escalations increased trough concentrations of infliximab; persistent increase in fecal concentration of calprotectin, despite dose escalation, was associated with a lack of endoscopic response and remission. A significantly higher proportion of patients with antibodies to infliximab, identified by a drug-tolerant assay, dropped out of the study compared with patients without antibodies (P < .0001). In a post hoc analysis of data from a trial to test the effects of infliximab dose escalation on symptoms, we found that during maintenance therapy, the combination of fecal concentration of calprotectin and trough concentration of infliximab can guide dose adjustment and increase the chances for endoscopic response and remission. ClinicalTrialsRegister.eu EudraCT no: 2011-003038-14.Show less >
Show more >In the TAILORIX trial, no benefit could be shown by infliximab dose escalation based on pharmacokinetic (infliximab serum concentrations) and pharmacodynamic (biomarkers and symptoms) monitoring compared with dose escalation based on symptoms alone in patients with Crohn's disease (CD). We investigated whether integration of pharmacokinetic and pharmacodynamic monitoring can be used to evaluate responses to infliximab induction and maintenance therapy, based on findings from endoscopy. We performed a post hoc analysis of patients with CD included in a trial to test the effects of infliximab dose escalation, based on biomarkers and serum concentrations of infliximab, on symptoms (the Study Investigating Tailored Treatment With Infliximab for Active Crohn's Disease trial; n = 122). We analyzed data from this study to determine whether concentrations of biomarkers and serum concentrations of infliximab were associated with endoscopic outcomes (n = 116). The primary end points were endoscopic response (CD endoscopic index of severity decrease ≥50% from baseline), endoscopic remission (CD endoscopic index of severity, <3), and absence of ulcers at weeks 12 and 54 of infliximab treatment. Infliximab trough concentrations greater than 23.1 mg/L at week 2 and greater than 10.0 mg/L at week 6 were associated with endoscopic remission at week 12 (positive predictive values, 72% and 76%; negative predictive values, 65% and 59%, respectively). During maintenance therapy, we found evidence for an exposure-response relationship only after dose escalation; trough concentrations greater than 10.6 mg/L were associated with the absence of ulcers at week 54 (positive predictive value, 49%; negative predictive value, 92%). Low fecal concentrations of calprotectin during therapy were associated with endoscopic response and remission (P < .05). Dose escalations increased trough concentrations of infliximab; persistent increase in fecal concentration of calprotectin, despite dose escalation, was associated with a lack of endoscopic response and remission. A significantly higher proportion of patients with antibodies to infliximab, identified by a drug-tolerant assay, dropped out of the study compared with patients without antibodies (P < .0001). In a post hoc analysis of data from a trial to test the effects of infliximab dose escalation on symptoms, we found that during maintenance therapy, the combination of fecal concentration of calprotectin and trough concentration of infliximab can guide dose adjustment and increase the chances for endoscopic response and remission. ClinicalTrialsRegister.eu EudraCT no: 2011-003038-14.Show less >
Language :
Anglais
Audience :
Internationale
Popular science :
Non
Submission date :
2024-01-30T10:28:23Z