Konstantinos Papamichael1, Shana Rakowsky1, Claudio Rivera2, Adam S Cheifetz1, Mark T Osterman2. 1. Center for Inflammatory Bowel Diseases, Division of Gastroenterology, Beth-Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. 2. Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Abstract
Background and aim: Objective and more rigorous therapeutic outcomes are emerging as novel targets in Crohn's disease (CD). We investigated the association between maintenance serum infliximab trough concentrations and biochemical, endoscopic, or histologic remission in CD. Methods: This retrospective multicenter study involved consecutive CD patients treated with infliximab who had a serum C-reactive protein (CRP) measured within 1 week or endoscopic evaluation within 12 weeks of therapeutic drug monitoring between January 2010 and June 2016. Biochemical remission was defined as a normal CRP (≤5 mg/L). Endoscopic remission was defined as absence of any mucosal break (ulceration or erosion) or for patients with an ileocolonic resection, a Rutgeerts score of ≤i1. Histologic remission was defined as absence of active inflammation. Results: Seventy-one CRP levels and 96 colonoscopies from 110 CD patients were evaluated. Based on ROC analyses, infliximab concentration thresholds of 2.2, 9.7, and 9.8 μg/mL were found to be related with biochemical, endoscopic, and histologic remission, respectively. Multiple logistic regression analyses identified infliximab concentration ≥2.2 (OR 6.4; 95% CI, 1.5-27.1; P = 0.011), ≥9.7 (OR 3.6; 95% CI, 1.4-9; P = 0.006) and ≥9.8 μg/mL (OR 3.2; 95% CI, 1.3-7.9; P = 0.011) as variables independently associated with biochemical, endoscopic, and histologic remission, respectively. Conclusions: This study showed that higher maintenance infliximab trough concentrations are associated with more favorable rates of biochemical, endoscopic, or histologic remission in CD patients and that infliximab concentrations may differ based on the treatment goal.
Background and aim: Objective and more rigorous therapeutic outcomes are emerging as novel targets in Crohn's disease (CD). We investigated the association between maintenance serum infliximab trough concentrations and biochemical, endoscopic, or histologic remission in CD. Methods: This retrospective multicenter study involved consecutive CDpatients treated with infliximab who had a serum C-reactive protein (CRP) measured within 1 week or endoscopic evaluation within 12 weeks of therapeutic drug monitoring between January 2010 and June 2016. Biochemical remission was defined as a normal CRP (≤5 mg/L). Endoscopic remission was defined as absence of any mucosal break (ulceration or erosion) or for patients with an ileocolonic resection, a Rutgeerts score of ≤i1. Histologic remission was defined as absence of active inflammation. Results: Seventy-one CRP levels and 96 colonoscopies from 110 CDpatients were evaluated. Based on ROC analyses, infliximab concentration thresholds of 2.2, 9.7, and 9.8 μg/mL were found to be related with biochemical, endoscopic, and histologic remission, respectively. Multiple logistic regression analyses identified infliximab concentration ≥2.2 (OR 6.4; 95% CI, 1.5-27.1; P = 0.011), ≥9.7 (OR 3.6; 95% CI, 1.4-9; P = 0.006) and ≥9.8 μg/mL (OR 3.2; 95% CI, 1.3-7.9; P = 0.011) as variables independently associated with biochemical, endoscopic, and histologic remission, respectively. Conclusions: This study showed that higher maintenance infliximab trough concentrations are associated with more favorable rates of biochemical, endoscopic, or histologic remission in CDpatients and that infliximab concentrations may differ based on the treatment goal.
Authors: Andres J Yarur; Anjali Jain; Scott I Hauenstein; Maria A Quintero; Jamie S Barkin; Amar R Deshpande; Daniel A Sussman; Sharat Singh; Maria T Abreu Journal: Inflamm Bowel Dis Date: 2016-02 Impact factor: 5.325
Authors: Konstantinos Papamichael; Karen A Chachu; Ravy K Vajravelu; Byron P Vaughn; Josephine Ni; Mark T Osterman; Adam S Cheifetz Journal: Clin Gastroenterol Hepatol Date: 2017-03-30 Impact factor: 11.382
Authors: Orlaith B Kelly; Sarah Oʼ Donnell; Joanne M Stempak; A Hillary Steinhart; Mark S Silverberg Journal: Inflamm Bowel Dis Date: 2017-07 Impact factor: 5.325
Authors: Konstantinos Papamichael; Thomas Van Stappen; Niels Vande Casteele; Ann Gils; Thomas Billiet; Sophie Tops; Karolien Claes; Gert Van Assche; Paul Rutgeerts; Severine Vermeire; Marc Ferrante Journal: Clin Gastroenterol Hepatol Date: 2015-12-08 Impact factor: 11.382
Authors: Jean-Frederic Colombel; Remo Panaccione; Peter Bossuyt; Milan Lukas; Filip Baert; Tomas Vaňásek; Ahmet Danalioglu; Gottfried Novacek; Alessandro Armuzzi; Xavier Hébuterne; Simon Travis; Silvio Danese; Walter Reinisch; William J Sandborn; Paul Rutgeerts; Daniel Hommes; Stefan Schreiber; Ezequiel Neimark; Bidan Huang; Qian Zhou; Paloma Mendez; Joel Petersson; Kori Wallace; Anne M Robinson; Roopal B Thakkar; Geert D'Haens Journal: Lancet Date: 2017-10-31 Impact factor: 79.321
Authors: Laurent Peyrin-Biroulet; Walter Reinisch; Jean-Frederic Colombel; Gerassimos J Mantzaris; Asher Kornbluth; Robert Diamond; Paul Rutgeerts; Linda K Tang; Freddy J Cornillie; William J Sandborn Journal: Gut Date: 2013-08-23 Impact factor: 23.059
Authors: Jurij Hanžel; Nejc Sever; Ivan Ferkolj; Borut Štabuc; Nataša Smrekar; Tina Kurent; Matic Koželj; Gregor Novak; Griet Compernolle; Sophie Tops; Ann Gils; David Drobne Journal: United European Gastroenterol J Date: 2019-03-19 Impact factor: 4.623
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