Konstantinos Papamichael1,2, Filip Baert3, Sophie Tops2, Gert Van Assche1, Paul Rutgeerts1, Severine Vermeire1, Ann Gils2, Marc Ferrante4. 1. KU Leuven, Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders [TARGID], and University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium. 2. KU Leuven, Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium. 3. Department of Gastroenterology, AZ Delta, Roeselare, Belgium. 4. KU Leuven, Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders [TARGID], and University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium marc.ferrante@uzleuven.be.
Abstract
BACKGROUND AND AIMS: Mucosal healing is associated with favourable therapeutic outcomes in patients with ulcerative colitis [UC]. We investigated whether adalimumab concentrations during induction therapy are associated with short-term mucosal healing [STMH] in UC patients. METHODS: This was a retrospective, single-centre study including consecutive UC patients treated with adalimumab from June 2005 to May 2014, who underwent an endoscopy both at baseline and after induction therapy [weeks 8-14] and at least one serum sample available at week 2 and/or week 4. STMH was defined as Mayo endoscopic sub-score of ≤1 with a baseline sub-score of ≥2. Adalimumab concentrations were evaluated using an in-house developed enzyme-linked immunosorbent assay. RESULTS: The study population consisted of 43 patients, the majority of whom [n = 38] were prior infliximab failures; the rest showed primary non-response [PNR, n = 5]. Twelve patients [27.9%] achieved STMH. Patients with STMH had higher adalimumab concentrations at week 4 compared to those without [10.6 vs 7.4 μg/ml, p = 0.014]. A receiver operating characteristic [ROC] analysis identified an adalimumab concentration threshold at week 4 of 9.4 μg/ml (area under the ROC curve [AUROC]: 0.778) and 7.5 μg/ml [AUROC: 0.798], after excluding patients with PNR to infliximab, to be associated with STMH. Multiple logistic regression analysis, after excluding patients with PNR to infliximab, identified adalimumab concentration ≥7.5 μg/ml at week 4 (odds ratio [OR]: 15.7; 95% confidence interval [CI]: 1.3-185; p = 0.029) and baseline endoscopic Mayo score 3 [OR: 0.13; 95% CI: 0.02-0.98; p = 0.047] as factors independently associated with STMH. CONCLUSIONS: This study, reflecting real-life clinical practice, demonstrated that post-induction adalimumab concentrations are associated with STMH, while higher baseline mucosal inflammation is related to lack of STMH in UC.
BACKGROUND AND AIMS: Mucosal healing is associated with favourable therapeutic outcomes in patients with ulcerative colitis [UC]. We investigated whether adalimumab concentrations during induction therapy are associated with short-term mucosal healing [STMH] in UC patients. METHODS: This was a retrospective, single-centre study including consecutive UC patients treated with adalimumab from June 2005 to May 2014, who underwent an endoscopy both at baseline and after induction therapy [weeks 8-14] and at least one serum sample available at week 2 and/or week 4. STMH was defined as Mayo endoscopic sub-score of ≤1 with a baseline sub-score of ≥2. Adalimumab concentrations were evaluated using an in-house developed enzyme-linked immunosorbent assay. RESULTS: The study population consisted of 43 patients, the majority of whom [n = 38] were prior infliximab failures; the rest showed primary non-response [PNR, n = 5]. Twelve patients [27.9%] achieved STMH. Patients with STMH had higher adalimumab concentrations at week 4 compared to those without [10.6 vs 7.4 μg/ml, p = 0.014]. A receiver operating characteristic [ROC] analysis identified an adalimumab concentration threshold at week 4 of 9.4 μg/ml (area under the ROC curve [AUROC]: 0.778) and 7.5 μg/ml [AUROC: 0.798], after excluding patients with PNR to infliximab, to be associated with STMH. Multiple logistic regression analysis, after excluding patients with PNR to infliximab, identified adalimumab concentration ≥7.5 μg/ml at week 4 (odds ratio [OR]: 15.7; 95% confidence interval [CI]: 1.3-185; p = 0.029) and baseline endoscopic Mayo score 3 [OR: 0.13; 95% CI: 0.02-0.98; p = 0.047] as factors independently associated with STMH. CONCLUSIONS: This study, reflecting real-life clinical practice, demonstrated that post-induction adalimumab concentrations are associated with STMH, while higher baseline mucosal inflammation is related to lack of STMH in UC.
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
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: E L Johnston; B D Warner; J L Digby-Bell; N Unsworth; S Anderson; J D Sanderson; Z Arkir; P M Irving Journal: Frontline Gastroenterol Date: 2016-11-29
Authors: Konstantinos Papamichael; Anna Juncadella; Danny Wong; Shana Rakowsky; Lindsey A Sattler; James P Campbell; Byron P Vaughn; Adam S Cheifetz Journal: J Crohns Colitis Date: 2019-08-14 Impact factor: 9.071