Noninvasive Targeted Crohn Disease Management by Combining Endoscopic Healing Index and Therapeutic Drug Monitoring

• Type of Material: Article
• Authors: Amy Hemperly, University of California San Diego; Marla C Dubinsky, Icahn School of Medicine at Mount Sinai; Andres Yarur, Medical College of Wisconsin; Anita Afzali, The Ohio State University Wexner Medical Center; Stephen Hanauer, Northwestern University Feinberg School of Medicine; Subramaniam Kugathasan, Emory University; Millie D Long, The University of North Carolina at Chapel Hill; Shervin Rabizadeh, Cedars-Sinai Medical Center; Robbyn Sockolow, Weill Cornell Medicine; Lauren Okada, Prometheus Laboratories; Anjali Jain, Prometheus Laboratories; Maria T Abreu, University of Miami Leonard M. Miller School of Medicine; Niels Vande Casteele, University of California San Diego
• Language: English
• Date: 2021-07-01
• Publisher: Oxford University Press
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2021. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1093/crocol/otab035
• Title of Journal or Parent Work: Crohn's and Colitis 360
• Volume: 3
• Issue: 3
• Start Page: 1
• End Page: 8
• Grant/Funding Information: Endoscopic healing index and therapeutic drug monitoring testing was performed by Prometheus Biosciences. A.H. and N.V.C. hold a Research Scholar Award from the American Gastroenterological Association. The study was supported in part by the Digestive Diseases Research Center grant NIH DK120515.
• Keywords: inflammatory bowel disease; biomarker; treat-to-target; endoscopic remission

Abstract

Background and Aims: Therapeutic drug monitoring (TDM) with measurement of serum drug and antidrug antibody concentrations is used to optimize tumor necrosis factor antagonists (anti-TNF). The endoscopic healing index (EHI) is a validated serum-based assay to measure mucosal inflammation in adults with Crohn disease (CD). Our objectives were to evaluate the relationship between EHI and TDM results and to determine the anti-TNF concentration range associated with EHI <20 (consistent with endoscopic remission). Methods: Adult and pediatric patients with CD (N = 1731) were selected retrospectively from a clinical laboratory cohort. Patients were selected if they had an ICD-10 code for CD and if results for EHI and TDM were available within 30 days of each other. The relationship between EHI and TDM results was examined and the anti-TNF concentration range associated with EHI <20 vs >50 was evaluated. Results: Median anti-TNF concentration was higher in patients with EHI <20 vs >50 for infliximab (N = 796): 11.1 vs 3.4 μg/mL and for adalimumab (N = 935): 9.2 vs 5.0 μg/mL (P < 0.0001 both drugs). Patients with antibodies to infliximab (12.8%) or adalimumab (14.9%) had lower anti-TNF concentrations (P < 0.001 both drugs) and higher EHI (P < 0.01 both drugs). The concentration range for infliximab: 5-15 μg/mL (5-9 μg/mL in pediatric patients) and for adalimumab: 5-10 μg/mL (8 μg/mL in pediatric patients) best discriminated EHI <20 vs >50. Conclusions: We report the anti-TNF concentration range associated with EHI <20. Combined testing of EHI and TDM is proposed as a noninvasive approach for treat-to-target management which could improve the ability to monitor disease and optimize anti-TNF therapy.